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第十一届全国博士生学术年会—生物医药专题

第十一届全国博士生学术年会—生物医药专题

  • 召开年：2013
  • 召开地：成都
  • 出版时间： 2013-11-08

主办单位：中国药学会;中国科协

会议文集：第十一届全国博士生学术年会—生物医药专题论文集

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  • 摘要：脆性X综合症是由于Fmr1基因中CGG重复序列过度扩展引起的一种遗传性智力低下症.最近的研究表明星形胶质细胞在神经元的发育中起重要作用.然而,星形胶质细胞在调节过程中所涉及的机制仍不清楚.研究发现,脆性X综合症来源的星形胶质细胞由于不表达FMRP,能抑制体外培养神经元的树突生长.此外,星形胶质细胞条件培养液和前额叶皮层均显示脆性X综合症中NT-3升高,而NGF、BDNF、GDNF和CNTF无变化.通过RNA结合蛋白免疫沉淀实验,发现在星形胶质细胞中,FMRP蛋白结合NT-3基因,抑制其蛋白表达.NT-3中和抗体和shRNA可以显著降低NT-3引起的神经元形态和突触蛋白水平异常.在基因敲除小鼠的前额叶皮层微量注射NT-3的shRNA可以改善恐惧记忆,并且伴随前额叶皮层的NT-3水平下降.这项研究表明,星形胶质细胞来源的NT-3分泌过量可导致神经元树突发育异常,因此星形胶质细胞可能是治疗脆性X综合症的一个潜在治疗靶点.
  • 摘要：Multiple species of natural and cultured Cordyceps are widely used as Chongcao,a well-known traditional Chinese medicines,for medicinal purpose in China.Small molecules such as nucleosides and sterols are greatly variant among different species of natural and cultured Cordyceps.However,there are few reports on polysaccharides,one of the major active components,in Cordyceps.In this study,Polysaccharides from seven different species of natural and cultured CordycePs were firstly investigated and compared using saccharide mapping,enzymatic(α-amylase,β-glucanase and pectinase) digestion followed by polysaccharide analysis by using carbohydrate gelelectrophoresis analysis(PACE) and high performance thin layer chromatography(HPTLC) analysis,respectively.The results showed that 1,4-α-D-glucosidic,1,4-β-D-glucosidic and 1,4-α-D-galactosidic linkages were existed in natural and cultured C.sinensis,cultured C.militaris,C.gracilis and C.ciecadae.The similarity of polysaccharides from cultured C.militaris to natural C.sinensis was relatively high,which may contribute to rational use of the commercial Cordyceps products,and helpful for development of cultured Cordyceps as a source of polysaccharides in natural C.sinensis.Moreover,different species of natural and cultured Corcdyceps can be differentiated based on the saccharide mapping,which is helpful to well understand the structural characters of polysaccharides from different species of Cordyceps and to improve the quafity control of polysaccharides in natural.
  • 摘要：目的:研究刺五加叶提取物对脑缺血大鼠的保护作用并探究其主要成分金丝桃苷、1,5-二咖啡酰奎宁酸和槲皮素在假手术大鼠和缺血大鼠脑内的药动学.方法:以结扎大鼠双侧颈总动脉方式建立急性不完全性脑缺血模型,采用微透析技术取样,液质联用分析方法在线检测不同组别大鼠脑透析液中五羟色胺及多巴胺的水平变化.舌下静脉给药刺五加叶提取物,比较主要成分在假手术大鼠及缺血大鼠脑内的药动学差异.结果:刺五加叶提取物中三种主要成分在大鼠脑内代谢迅速,约三小时即消除完全.同假手术组相比,脑缺血模型组大鼠脑组织内的多巴胺和五羟色胺的水平均显著升高;给药刺五加叶提取物注射液组及阳性对照曲克芦丁注射组的脑缺血大鼠脑内两物质水平较模型组有明显降低.结论:刺五加叶提取物中三种主要成分均能透过血脑屏障到达脑部发挥作用,能够对脑缺血大鼠脑内多巴胺及五羟色胺水平进行正向调节,在一定程度上起到对脑缺血大鼠的保护作用.
  • 摘要：Tumor-oriented nanocarrier drug delivery approaches with pH-sensitivity have been drawing considerable attentions over the years.Here we describeda liposomal delivery system modified withpH-responsive cell penetrating peptide TH(TH-Lip).Conventional cell penetrating peptide(CPP)-related drug delivery tactics sometimes seemed limited due to the extensiveto in vivo penetration and the lack of proper selectivity of conventional CPPs.In this study,TH(AGYLLGHINLHHLAHL(Aib)HHIL-NH2),an engineered α-hefical cell penetrating peptide originated from peptide TK(AGYLLGKINLKKLAKL(Aib)LLIL,-NH2),was endowed pH-responsiveness after complete replacement of all lysines in the sequenceof TK into hisdines,and was introduced onto the surface of liposomes.Accordingly,TH-Lip could benefit from the unique property of TH,as the cell penetrating capacityof TH was concealed during the blood circulation and in normal tissues because of theneutral pH under those conditions.However,when TH-Lip reached the tumor,and aspH declined,hisitidines in TH peptide protonated and the surface charge of TH-Lipconverted from negative to positive,initiating activated cell penetrating capacity and leading toenhanced cellular and tumor spheroid uptake.The endocytosis inhibition assay demonstrated that the endocytosis of TH-Lip was influenced by the positively charged surface of the liposomes in acidic environment and was mediated by clathrin,and the intracellular trafficking study suggested that the liposomes were mainly accumulated in endoplasmic reticulum and Golgi apparatus.After systemic administration in mice,TH-Lip could be internalized into tumor cells efficaciously.When it comes to the delivery of pacfitaxel (PTX),the pH-responsiveness of TH-Lip led to strong inhibition against tumor cell growth which occurred both in vitro(underpH 6.3) and in vivo,and the tumor inhibition rate reached 86.3% on C26 tumor-bearing mice for PTX-loaded TH-Lip.Therefore,TH-Lip proved itself to be a promising pH-responsive strategy for drug delivery within acidified tumor microenvironment.
  • 摘要：Asymmetric chlorolactonization reaction of alkenes is one most important reactions in organic chemistry due to the resulting chiral3,4-Disubstituted is ocoumar in is the fundamental unit of many compounds that possess a wide spectrum of biological activity.We have developed a more practical and efficient catalytic asymmetric chlorolactonization of styrene-type carboxylic acids with DCDMH using C3-symmetrical cinchonine-squaramide(CSCS) as organocatalyst.Series of chiralchloro substituted isochroman-1-ones were obtained in excellent yields(up to 99%)and enantioselectivities(up to 99% ee).To the best of our knowledge,the results are the best ever achieved.Moreover,in our case,the asymmetric hctonization is stereospecific,with use of terminal alkenes forming 5-exo products,while 6-endo chloro substituted isochroman-1-ones were obtained in higheree values when internal alkenes was used in the reaction.Furthermore,the nature ofcarboxylic acid has significant influence on the enantioselectivity.The reaction of carboxylic acids bearing an electron-withdrawing group on the phenyl ring afforded the corresponding products in higher ee.Gratefully,in this asymmetric transformation,our easily available C3-symmetrical CSCS organocatalyst can berecovered and reused for six cycles without losing the activity and enantioselectivity.The methodology has provided a convenient approach for the synthesis of optical pure isochro man-1-one derivatives.In addition,further studies indicated that the optical pure isochroman-1-one products exhibit potent anti-HIV activity.
  • 摘要：A facile synthesis of a potent SGLT2 inhibitor 6-deo xydapagliflozin frommethyl 2,3,4-tri-O-benzyl-6-deoxy-6-iodo-α-D-glucopyranoside in 6 steps in 50% overall yield is described.The key steps were the reductive deiodination of thestarting iodide under hydrogenolys is condition to build the desired 6-deoxyglucose functionality and the coupling of 2,3,4-tri-O-benzyl-6-deoxy-D-gluconolactone and(5-bromo-2-chlorophenyl)(4-ethoxyphenyl)methane followed by BF3·Et2O-mediatedreduction with Et3SiH to construct the desired anomericp β-configuration.A variety of methods used for the cleavage of benzyl groups in2,3,4-tri-O-benzyl-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,6-dideoxy-β-D-glucopyranose were intensively screened,leading to the discovery of AlCl3-mediated cleavageas the optimal method.
  • 摘要：Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia gigantifolia stapf and one potential anti-tumor saponin was methanolysised by H2S04 to afford four new compounds.The seventeen compounds were evaluated for theiranti-proliferative activity on A549,HCT-8 and Bel-7402 cells.The structure-activityre lationship analysis indicated that the incorporation of =O group at C-16,L-rhamnose at R5 and acetyl group at OH-6 of the D-glucose lead to a significant increase of the cytotoxic activity on A549 and HCT-8 but significant reduction of thecytotoxic activity on Bet-7402 cells.The synthesized saponins losing 13,28-epoxyand CHO at C-30,losed their cytotoxicities on A549 and HCT-8 cells,suggesting that the two moieties play an essential role for activity.3(β-O-α-L-rhamnopyranosyl-(1→3)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranoside-16α,-hydroxy-13,28-ep oxy-oleanane (2) showed better inhibitory activity to Bet-7402(IC50 0.86μM) thanthat of 5-FU(IC50 8.30μM),which indicate that five saccharide and methyl moietyat C-30 are important for anti-proliferative activity.The activities of saponins 15>14,17>16,suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather than 30(S) on Bel-7402 cells.Further molecular mechanism studies of saponins1 and 2 were carried out on the cell cycle distribution of Bet-7402 cells.
  • 摘要：目的:研究金匮肾气丸干预肾阳虚证大鼠内源性代谢物的变化,探索与肾阳虚证密切相关的代谢物、代谢通路及其治疗作用.方法:检测大鼠血清ACTH,CORT,T3,T4,TSH,以及组织形态学观察.基于UPLC-HDMS的方证代谢组学技术平台,对大鼠尿液进行模式识别分析,研究肾阳虚证生物标记物及金匮肾气丸相应的治疗作用.结果:模型大鼠的ACTH、CORT、T3、T4,TSH含量显著下降,HPA,HPT轴均出现抑制现象.金匮肾气丸可显著提高血清中CORT、T3、T4含量,血清中TSH,CORT有显著升高趋势.确定12个肾阳虚证模型的生物标记物,如牛磺酸,脯氨酸羟脯氨酸,烟酰胺等,涉及牛磺酸代谢,苯丙氨酸代谢和组氨酸代谢途径.发现金匮肾气丸对这些标记物均具有明显的回调作用.结论:成功运用方证代谢组学方法建立了“肾阳虚证—金匮肾气丸—生物标记物”三维模式,发现金匮肾气丸通过改善多个代谢通路,使代谢组轮廓整体回调,证明了中医“方证对应”思想的科学性,并体现出金匮肾气丸治疗作用的多途径、多靶点、整体调节的特点.
  • 摘要：Aim of the study:To explore the effects and potential mechanism of SM against hepatic fibrosis induced by chronic iron overload in mice.rn Materials and methods:Sixty male mice were randomized into five groups(n=12 ineach group):control(saline),iron overload,iron overload with low-dose SM(3 g/kg/day),iron overload with high-dose SM(6 g/kg/day) and iron overload with deferoxamine(100 mg/kg/day) groups.The iron overload model was established by intraperitoneal injection with iron dextran at 50 mg/kg body weight/day,and the entire course lastedfor 7 weeks.The major constituents of SM injection were quantified by high performance liquid chromatography.Changes of hepatic iron,hydroxyproline(Hyp),glutathione(GSH),superoxide dismutase(SOD) and malondialdehyde(MDA) were assayed by standard procedures.Protein expression levels of type Ⅰ collagen,type Ⅲ collagen,tumor necrosis factor-α(TNF-α) and interleukin-1α(IL-1α) were analyzed by immunohistochemistry,and mRNA levels of transforming growth factor-β(TGF-β),matrixmetal proteinase-9(MMP-9) and caspase-3 were detected by RT-PCR.Morphological changes were observed with Prussian blue,Masson's triclnome and hematoxylin-eosin staining.rn Results:Treatment of chronic iron-overloaded micewith SM dose-dependently ameliorated changes in hepatic morphology and coefficient,reduced iron depositionand Hyp content,suppressed over expression of type Ⅰ collagen and type Ⅲ collagen,downregulated expression of TGF-β mRNA,and upregulated expression of MMP-9mRNA in the liver.Moreover,SM treatment contributed to decreased MDA content,increased SOD activity and GSH content,while it reduced expression of TNF-α,IL-1α and caspase-3.rn Conclusions:SM displayed anti-fibrotic activity in the liver induced by chronic ironoverload,which may be attributed to multitargeted inhibition of iron deposition and collagen accumulation,as well as oxidative stress,inflammation and apoptosis.
  • 摘要：Arsenic trioxide(As2O3) is a notorious human poison, but can be used therapeutically to treat acute promyelocytic leukemia and some solid tumors.However,the clinical use of As2O3 is limited by its severe toxic side-effects.Combination therapy with potent antioxidant may allow for administration of lower doses of As2O3,minimizing toxicity and potential drug resistance.Moreover,anti-oxidative agent could also provide possible approaches to reduce toxicity of environmental exposure of As2O3.In this study,the protective effects of resveratrol,apolyphenol natural antioxidant,against As2O3-induced oxidative damage wererevealed.Our results demonstrated that co-treatment of human bronchial epithelial cell with 5μM resveratrol for 24h remarkably reduced the levels of 20μM As2o3-induced reactive oxygen species(ROS) generation,lipid peroxidation,chromosomal and DNA damage,and cell apoptosis.Resveratrol was also shown to markedly reduce the increased activities of caspase-8,9 and 3 and inhibit the Fas,Fas-L,cytochrome c and caspase-3 over expression induced by As2O3.Additionally,significantly elevated glutathione(GSH) and the activities of its relevant enzymes as well as the up-regulated the GCLC and GCLM expression further indicated that resveratrol ameliorated As2O3 toxicity through modulation of GSH biosynthesis,recycling and utilization process.In summary,our results reveal that resveratrol attenuate As2O3-induced oxidative damage via maintenance of GSH homeostasis and inhibition of both death receptor and mitochondrial apoptotic pathways in the lungcells.These observations suggest that resveratrol has the potential to protect againstAs2O3 toxicity in both clinical use and environment exposure of As2O3.
  • 摘要：铅(Pb)是环境中最重要的无机污染物之一,可影响体内氧自由基清除酶的活性,导致氧化应激,具有明显的肾损伤作用.普洱茶为云南特色名茶,其成分中的茶多酚及儿茶素促排铅效果明显.本文在清楚了解铅造成肾脏炎症损伤机制的基础上,探讨普洱茶的促排铅效果及对铅造成的肾脏炎症损伤的保护作用.首先,利用低剂量醋酸铅建立慢性长期铅暴露模型,观察慢性铅暴露对小鼠全血铅和肾脏组织铅水平的影响,检测铅暴露对肾脏组织中炎症因子TNF-α水平的影响,为解释现象,检测肾脏组织中羰基化合物MG的水平,羰基化终末产物AGEs、RAGE蛋白表达水平,核转录因子NFKB磷酸化水平.然后利用不同剂量的普洱茶灌胃铅暴露模型鼠,检测普洱茶对小鼠全血铅水平和肾脏组织中羰基化合物MG水平的影响.结果显示,慢性长期铅暴露实验中,铅进入机体后短时间内即能蓄积在肾脏,且对肾脏造成炎症损伤,该损伤与暴露时间呈正比.动物实验证明铅造成该损伤的机制是慢性铅暴露导致肾脏组织中羰基化合物MG的过量累积,产生大量的AGEs,引起相应的受体蛋白RAGE表达上调,磷酸化核转录因子NFΚB入核,最终造成肾脏组织TNF-α含量增加,导致炎症损伤.而一定浓度的普洱茶不仅能够起到促排铅效果,还能直接螯合组织中的MG,减少MG的过量累积,降低RAGE蛋白的表达,减缓后续炎症损伤,降低TNF-α的量.
  • 摘要：目的:研究表明口服β-1,3-D-葡聚糖可被巨噬细胞识别,并分布于全身单核巨噬系统.而在炎症相关疾病中,巨噬细胞可通过募集作用聚集于病灶部位.本文拟基于巨噬细胞β-1,3-D-葡聚糖识别作用构建口服炎症靶向药物递送系统.方法:通过酸碱及有机溶剂处理酵母菌制备酵母微囊,通过酵母微囊内吲哚美辛与聚乙烯亚胺自组装形成吲哚美辛酵母微囊,并对该载药微囊的体内外药动学及抗炎疗效进行评价;制备量子点酵母微囊,并采用裸鼠足趾肿胀模型口服后活体成像观察全身荧光分布验证其口服炎症靶向特性.结果:成功制备了吲哚美辛酵母微囊,该微囊具有酸性环境下不释放,碱性环境下快速释放的特性,并可显著提高吲哚美辛口服生物利用度及抗炎疗效.口服量子点酵母微囊后,在裸鼠关节炎症部位荧光明显增强,表明量子点可通过酵母微囊转运靶向于炎症部位.结论:酵母微囊可通过巨噬细胞识别作用口服靶向至炎症部位,并显著提高吲哚美辛的抗炎疗效,证实了基于巨噬细胞β-葡聚糖识别作用构建口服炎症靶向药物传递系统的有效性及可行性.
  • 摘要：目的:将磁性微粒的快速分离效应与酶标噬菌体抗体产生的信号放大效应相结合,有效实现对检测靶分子的捕获和分离,建立灵敏度高、特异性强的毒素检测方法.方法:将磁性微粒偶联多抗作为毒素捕获探针,酶标噬菌体抗体作为特异信号检测探针,采用“磁性微粒偶联多抗-毒素-酶标噬菌体抗体”模式的磁酶免疫分析法检测微量β-BGT.结果:该法检测β-BGT线性范围为0.016～62.5μg/L,线性回归方程为Y=0.641X+1.355(R2=0.985,n=13,P<0.0001),检测限为0.016μg/L,能满足水样、土样、食品及血液等模拟样品的分析要求,具有较好特异性与重现性.结论:成功建立了基于酶标噬菌体抗体的磁酶免疫分析法检测β-BGT,提高了检测灵敏度和特异性,可适用于各种微量β-BGT样品的分析.
  • 摘要：中药丹参和黄芩具有多种药理作用,如抗病毒、抗菌及抗真菌活性、清热解毒作用、降压作用等,但对这两种中药抗肿瘤活性成分的研究较少.本文利用高表达EGFR细胞制备细胞膜色谱柱并通过十通切换阀与HPLC/MS构建成二维在线联用系统.高表达EGFR细胞膜色谱柱的特异性、选择性、重现性、色谱柱活性时间均能满足实验要求.并成功的利用该系统从丹参超临界提取物及黄芩总提取物中筛选出能够作用于EGFR的活性成分阴丹参酮和汉黄芩素.分子模拟对接实验表明阴丹参酮和汉黄芩素与EGFR的相互作用方式与阳性药吉非替尼相似.通过MTT实验研究吉非替尼、阴丹参酮、汉黄芩素对高表达EGFR细胞的体外抑制作用,研究表明在浓度为0.5-50μM范围内,吉非替尼、阴丹参酮、汉黄芩素对高表达EGFR细胞的体外抑制作用具有剂量依赖性.EGFR细胞膜色谱在线HPLC/MS系统将成为一种从中草药中发现潜在抗肿瘤候选药物的有效方法.
  • 摘要：中国分布的49种薯蓣属植物中,值得注意的是,只有穿龙薯蓣、黄山药和盾叶薯蓣这三种被成功开发为有效治疗心血管疾病的药物并已应用数十年.为避免这三种药材的伪品和掺杂,本文采用性状和显微鉴定的方法,联用普通光学显微镜、荧光显微镜和偏光显微镜对药材横切面进行观察.尤其是,首次应用了偏光显微镜观察药材横切面,能得到更多鉴别特征.除此之外,也采用药材粉末显微鉴别作为辅助手段进行鉴别.结果表明,利用药材横切面观察到的淀粉粒、木化薄壁细胞以及其他有显著特征的组织,能够对三种药材进行鉴别.该方法快速、方便、有专属性且简单.
  • 摘要：目的:通过靶向抑制原癌基因Bmi-1表达,观察其诱导胆囊癌细胞凋亡及上调Caspase-3蛋白表达的效应,探讨其在胆囊癌形成中的分子机制.方法:通过前期成功构建miRNA-Bmi-1重组质粒转染GBC-SD细胞株,然后将其分为miRNA-Bmi-l group、miRNA-Scramble group、Lipofectamine group、GBC-SDgroup,转染48h后采用RT-PCR和Western blot法检测各组Bmi-mRNA和蛋白的表达,倒置显微镜观察各组细胞生长情况;流式细胞技术检测各组细胞的凋亡率、细胞周期分布情况及Caspase-3蛋白表达水平.结果:成功转染miRNABmi-l重组质粒48h后,RT-PCR和Western blot结果显示重组质粒组胆囊癌细胞Bmi-1 mRNA和蛋白的表达水平均明显低于对照组(P<0.05),表明miRNA-Bmi-1能有效抑制GBC-SD细胞的衷达.倒置显微镜观察显示miRNABmi-1组细胞死亡较对照组明显;细胞周期检测显示:m缺NABmi-1重组质粒组细胞阻滞于GO/GI(72.20+1.71),G2/M和S期细胞减少(18.30+7.21,9.50+6.01),凋亡指数增高(49.83+5.19),Caspase-3蛋白表达量明显增加,与对照组比较,具有显著性差异(p<0.05).结论:靶向沉默Bmi-1能有效抑制胆囊癌细胞Bmi-1mRNA及蛋白表达,诱导胆囊癌细胞凋亡,其机制可能是早期使胆囊癌细胞周期阻滞于GO/GI期,并上调Caspase-3蛋白表达,Bmi-1可能参与调控线粒体依赖的凋亡途径.
  • 摘要：肝脏中含有许多代谢酶,大多数外源物质都是在肝脏中被代谢排放的.随着化学及生物合成工业的发展,大量新药被开发并有待筛选.一种新药在临床试验前,必须检测它的安全性和可能出现的药物与药物之间的相互作用.利用静电纺丝和共培养技术,成功的在体外构建了共培养肝细胞模型用于药物筛选,研究发现,与肝细胞单独培养比较,共培养培养的肝细胞能较长时间地保持酶的活性,而且酶活性也更高.另外,测定了肝细胞对五种药物的代谢能力,由于肝细胞和成纤维、内皮细胞共培养组具有较好的CYP450酶活,它能较为准确的作为药物筛选的模型,明显优于肝细胞单独培养组.采用利福平,酮康唑来分别测定药物对共培养组的诱导和抑制,结果显示肝细胞和成纤维、内皮细胞这三种细胞共培养能很好地响应药物的诱导和抑制.
  • 摘要：本文以中药墨旱莲为原料,经过水提、超滤、醇沉得到粗多糖部位.通过活性导向的方法经过系统的分离纯化,得到一个具有抗补体活性的均一多糖EAP20-2.,经HPGPC法检测为均一多糖,计算平均分子量为6.3x103Da.采用糖组成分析、,绝对构型分析、甲基化分析、NMR等方法进行结构鉴定.分析结果表明,EAP20-2主要由半乳糖Gal、葡萄糖Glu组成,并含少量的阿拉伯糖Ara,摩尔比为6526.5:8.5.单糖绝对构型均为D构型,比旋光度为-25°,主链由β-D-1,4一Gal,β-D-1,6-Gal和α-D-1,4,6-Glc组成,并含少量的β-D-1,4-Glc.非还原末端末端为Glc.而少量的阿拉伯糖通过α-Araf和α-1,5-Araf连接形成阿拉伯聚糖支链.通过体外抗补体活性实验的经典途径和旁路途经检测,EAP20-2的CP50值为0.12+0.02mg/ml,AP50值为0.27+0.0lmg/ml.抗补体作用靶点的检测表明EAP20-2作用于补体Clq、Clr、Cls、C2、C4、C5、C7和C9组分上.抗凝血试验表明EAP20-2不具有抗凝血作用.
  • 摘要：目的:病毒特异性T细胞功能抑制是HIV-1慢性感染期的重要特点;也是病毒持续感染的重要因素.感染后Treg细胞增加参与了T细胞功能抑制的形成.另一方面,慢性感染者常具阳虚证型.通过研究温阳药物(喘可治)对SIV感染猴模型的Treg/Th17平衡的影响,将加深对HIV免疫病理机制、以及温阳药物的调节机制的认识.方法:12只感染SIV的中国恒河猴,分为治疗组和对照组,治疗组每天给予肌肉注射喘可治注射液,对照组注射生理盐水,连续3个月;定期冻存外周血单个核细胞(PBMC).复苏后进行Treg.Th17的流式分析.结果:喘可治治疗后,病毒载量、总CD4、CD8细胞数的改变不明显;治疗组CD25+FoxP3+Treg细胞数有减少趋势,而对照组则略有增加;治疗组CD25-FoxP3+亚群也有减少趋势,其下降幅度大于对照组;CD25+FoxP3-在对照组明显增加、而治疗组略有减少,两组间有统计学差异(P<0.05),其意义尚不清楚.治疗后两组Th17细胞数及Th17/Treg比例均有所降低,组间差异不明显.结论:喘可治可降低SIV慢性感染猴的Treg细胞,但并不能改变Th17/Treg的平衡.
  • 摘要：肿瘤恶病质是恶性肿瘤并发的以进行性肌肉萎缩和体重减轻为主要特征的多系统综合征,其发病率和死亡率高,严重影响患者的生活质量和干预肿瘤治疗进程,致使病人机体功能障碍和生存期缩短,目前临床上缺乏有效的治疗药物和治疗方法.而其发生机制目前主要有细胞因子学说、蛋白降解学说、负氮代谢学说等.姜黄素能有效抑制体内炎症,减少细胞因子的产生,抑制泛素化蛋白降解系统的关键蛋白的产生和活化,进而延缓恶病质肌肉萎缩的过程,其药效研究已有多篇文献确认,但其对机体代谢的影响尚未见报道.本文基于肿瘤恶病质发生过程中的代谢改变,采用代谢组学方法,研究恶病质发生发展过程中的关键性代谢改变和姜黄素对恶病质的代谢通路干预机制.结果显示,肿瘤恶病质发生过程中除了上升的糖酵解外,基于1H的核磁共振图谱显示了25个特异性相关代谢物,氨基酸代谢的经时变化规律确认了恶病质存在不同于肿瘤的代谢改变.而姜黄素的治疗可以有效调节其亮氨酸、缬氨酸等支链氨基酸的生物合成,改变机体酮体合成和降解,影响牛磺酸、甘油酯、甘氨酸、丝氨酸和苏氨酸的代谢,这些代谢的改变确认了姜黄素对肿瘤恶病质特异性的代谢通路的干预作用和其有效纠正恶病质高代谢状态的药物治疗潜能.
  • 摘要：目的:研究丹酚酸B(SaIB)对脑缺血再灌注损伤大鼠炎症反应的干预作用.方法:雄性Wis tar大鼠随机分为假手术组、模型组、SalB组,制作脑中动脉闭塞模型(MCAO),缺血th再灌注.SaIB组分别于大鼠苏醒后、再灌注24h和48h腹腔注射SalB(12mg/kg),模型组以等体积生理盐水替代.在4个时间点(6h、24h、48h、72h)进行神经功能缺损评分,全自动血球分析仪检测外周血白细胞计数及中性粒细胞绝对值,ELISA法检测血浆C反应蛋白水平,实时荧光定量RT-PCR检测缺血侧脑组织ICAM-1、E-sele ctin mRNA的表达.结果:SaIB可以改善模型大鼠神经功能缺损症状,降低外周血白细胞计数、中性粒细胞绝对值、血浆CRP水平、抑制缺血侧脑组织ICAM-1、E-sele ctin mRNA表达.结论:SaIB具有抗脑缺血再灌注损伤作用,其机制与抑制损伤后整体炎症反应水平及脑组织内粘附分子的表达有关.
  • 摘要：Pyrethroid insecticide modulation of the voltage-gated sodium channel(VGSC) is proposed to underlie their effects on neuronal excitability by inhibiting channel inactivation and increasing channel open time.However,some in vitro evidences indicate that target sites other than VGSCs could contribute to pyrethroid disruption of neuronal activity.Cholinergic excitability in Drosophila,as in other insects and mammals,is important for activity in the central nervous system.The effects of permethrin,a putative calciumant agonist,on calcium current andcholinergic mini-synaptic transmission were investigated in the Drosophila brain.At concentration of 2.5μM,permethrin significantly decreased the calcium current and cholinergic mini-synaptic current.However,the permethrin could not antagonize the calcium current completely.Removal of calcium from the external solution produceda significant decrease of cholinergic mini-synaptic transmission.The results are consistent with the hypothesis that permethrin may modulate chofinergic mini-synapti ccurrents by partially blocking the calcium channel.
  • 摘要：The long-term performance of tissue-engineered bone grafts is determinedby a dynamic balance between bone regeneration and resorption.We proposed using embedded cytokine slow-releasing hydrogels to tune this balance toward a desirablefinal bone density.In this study we established a systems biology model,and quantitatively explored the combinatorial effects of delivered cytokines from hydrogels onfinal bone density.We hypothesized that:1)bone regeneration was driven by transcription factors Runx2 and Osterix,which responded to released cytokines,such as Wnt,BMP2,and TGFβ,drove the development of osteoblast lineage,and contributed to bone mass generation;and 2)the osteoclast lineage,on theother hand,governed the bone resorption,and communications between these two lineages determined the dynamics of bone remodeling.In our model,Intracellular signaling pathways were represented by ordinary differential equations,while the intercellular communications and cellular population dynamics were modeled by stochastic differential equations.Effects of synergistic cytokine combinations were evaluated by Loewe index and Bliss index.Simulation results revealed that the Wnt/BMP2 combinations released from hydrogels showed best control of bone regeneration and synergistic effects,and suggested optimal dose ratios of given cytokine combinations released from hydrogels to most efficiently control thelong-term bone remodeling.We revealed the characteristics of cytokine combinations of Wnt/BMP2 which could be used to guide the design of in vivo bone scaffolds and the clinical treatment of some diseases such as osteoporosis.
  • 摘要：过敏是机体对外界某些刺激或药物的感受性不正常的增高现象.本文建立了嗜碱性白血病细胞膜色谱与高效液相色谱/质谱在线联用系统(RBL-2H3/CMC-online-HPLC/MS),应用该系统筛选白胡椒乙醇提取物中的抗过敏成分.结果发现,胡椒碱在RBL-2H3细胞膜色谱上有较好的保留.同时,β-氨基己糖苷酶释放率实验表明,随着给药浓度的增加,胡椒碱可以显著性的降低β-氨基己糖苷酶的释放.本文建立的RBL-2H3/CMC-HPLC/MS在线联用系统可以选择性的从中药复杂体系中筛选目标组分,且筛选组分与其生物效应具有相关性.
  • 摘要：The recurrence of breast cancer is associated with the drug-resistance of cancer stem cells(CSCs),while the overexpression of cell membrane ATP-binding cassette(ABC) transporters and the resistance of mitochondrial apoptosis-re lated proteinsare responsible for the drug-resistance of CSCs.The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs,thereby treatingand preventing the relapse of breast cancer.Evaluations were performed on the human breast CSCs and the CSCs xenografts innude mice.The targeting berberine liposomes could transmembrane across CSCs,inhibit ABC transporters(ABCC1,ABCC2,ABCC3,ABCG2),selectively accumulatein the mitochondria,activate the pro-apoptotic protein Bax,suppress theanti-apoptotic protein Bcl-2,open the mitochondrial permeability transition pores,cause the release of cytochrome c,and activate caspase-9/caspase-3 enzymes.Thesignificant efficacy in mice was evidenced after the administrations,indicating thatthe targeting berberine liposomes would be a potential co-therapy to treat and prevent the relapse of breast cancers arising from CSCs.
  • 摘要：In an attempt to increase the interaction of a nanocarrier system with gastrointestinal epithelial cells,a transferrin-receptor(TfR) specific 7peptide was conjugated to PEG-b-PCL copolymer and the functional nanocarriers were constructed and characterized.The endocytosis, intracellular trafficking and transcytosis of such nanocarriers loaded with coumarin 6(7pep-M-C6) in a human colon carcinoma cell fine(Caco-2) were investigated,followed by the in vivo intestine distribution study The real-time imaging of five cell,three dimensional reconstruction of confocal image,quantitative colocafization analysis and other techniques were applied.First,the TfR expression was confirmed in Caco-2.Then,7pep-M-C6exhibited higher intracellular uptake compared with unmodified nanocarriers.In a five cell study,7pep-M-C6 demonstrated faster uptake kinetics especially in the surface ofcells.Together with a competition study using TfR antibody,it was proved that the increased cellular uptake was due to a receptor-mediated mechanism.Besides the unspecific endocytosis pathway,7pep-M-C6 was found to enter the cells through aspecific clathrin-mediated mechanism,related to the expression of TfR on Caco-2cells.Possibly for this reason,7pep-M-C6 tended to colocalize more with late endosomes and lysosomes than the control micelles. Also for the same mechanism,the increased transport of 7pep-M-C6 across Caco-2 monolayer was found,through atranscellular but not a paracellular pathway,while an increased in vivo intestinal distribution of 7pep-M-C6 was observed.In conclusion,the functional nanocarriers could specifically interact with gastrointestinal endothelial cells,increase their transport and alter their pathway as a result.
  • 摘要：RNA interference holds tremendous potential as a therapeutic approach ofmalignant tumors.However,safe and efficient nanovectors are extremely lack forsystemic delivery of small interfering RNA(siRNA).The study aimed to develop a biomimetic nanovector,reconstituted high density lipoprotein(rHDL),mediating targeted cholesterol conjugated siRNA(Chol-siRNA)delivery for Pokemon genesilencing therapy. Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were prepared using thin-film dispersion method and their characteristics were investigated in detail.RHDL/Chol-siRNA complexes at the optimal volumeratio(lipid:Chol-siRNA) exhibited high Chol-siRNA-loading efficiency(～99%),desirable nanoparticle size and excellent stability in serum.In addition,by analyzing Chol-siRNA release profile,rHDL/Chol-siRNA complexes disphyed sustained-release characteristic and storage stability.Observations from FACS and confocal microscopic analyses revealed that rHDL-mediated carboxyfluorescein tagged Chol-siRNA(FAM-Chol siRNA) transfection resulted in highly efficient uptake and specific cytoplasmic delivery of FAM-Chol-siRNA into human hepatocellular carcinoma cell line HepG2 via HDL-receptor mediated mechanism.In vitro cytotoxicity,apoptosis and Western-blot analyses revealed significant cellular growth inhibition and decrease of Pokemon and Bcl-2 protein expression in HepG2cells treated with Chol-siRNA-Pokemon-loaded rHDL nanoparticles(rHDL/Chol-siRNA-Pokemon complexes),respectively.In in vivo studies,the near-infrared(NIR) dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles(rHDL/Cy5-Chol-siRNA complexes) obviously accumulated in tumor of nude miceafter i.v.administration as compared with Cy5-Chol-siRNA-loaded lipoplexes (Lipos/Cy5-Chol-siRNA complexes).Morover,rHDL/Chol-siRNA-Pokemoncomplexes demonstrated great tumor growth inhibition and significant decrease ofPokemon and Bcl-2 protein expression in vivo.These results suggested that rHDL should be an ideal non-viral tumor-targeting vector for Chol-siRNA transfer, andrHDL-mediated Chol-siRNA-Pokemon delivery might be a promising new strategyfor gene therapy in hepatocellular carcinoma.
  • 摘要：目的:开发一系列有效的醛糖还原酶抑制剂.方法:以3-氯-喹喔啉-2(1H)-酮为母体结构,设计合成了一系列侧链含有不同取代基的喹喔啉酮衍生物并测定了目标化合物的醛糖还原酶抑制活性.结果:发现喹喔啉酮衍生物8a-f具有良好的体外醛糖还原酶抑制活性,其中,8b的体外活性最高,IC50值为0.032 μM,7位取代基为F以及6位取代基为F的化合物其活性都要高于母核苯环上含有其他取代基的化合物.结论:作为新型的醛糖还原酶抑制,侧链含有酚羟基的喹喔啉酮衍生物的开发潜力巨大.
  • 摘要：为了开发利用我国海洋资源,寻找具有重要生物活性和药用前景的海洋天然产物,对采自我国海南三亚亚龙湾海域的圆盘肉芝软珊瑚进行了系统的研究.从中共分离得到25个二萜化合物(16个为新化合物),其中2个二萜属于一种全新骨架,1个比较少见的两个二萜单体以酯键聚合的二萜二聚体,另外23个二萜属于软珊瑚中代表性的西松烷二萜.采用国际上流行的液态ECD/TDDFT量子化学计算法确定新骨架化合物的绝对构型.还成功地得到了2个西松烷二萜的晶体,分别应用铜靶单晶衍射(X-ray)这种方法,得出这2个化合物的绝对构型.这是首次确定了含有七元内酯环(α,β-不饱和ε-内酯)的西松烷二萜的绝对构型.
  • 摘要：目的:通过研究芫花与甘草反药合用对大鼠水盐代谢的影响,探讨两药相反的可能特征与机制.方法:大鼠分为对照组、芫花组、甘草组、芫花-甘草合用组,给药后测定尿量变化,尿液和血清中电解质Na+、K+、Cl+、Ca+、Mg2+水平,血清中抗利尿激素(AVP)和醛固酮(ALD)水平.结果:在药典剂量下,芫花具有较强的利尿作用,其利尿作用的机理可能是通过使AVP分泌减少,抑制肾小管对Na+的重吸收,从而促进Na+和水的排出;甘草对大鼠尿量无显著影响,血中AVP水平有增加的趋势,但并无显著性差异,对电解质也有一定的影响,表现为尿Na+排泄减少,尿K+排泄增加,血K+含量降低,提示甘草具有一定的“保钠排钾”作用;芫花与甘草合用甘草可抑制芫花的利尿作用,表现为血中AVP、ALD水平增加,尿Na+排泄减少,尿K+排泄增加,血K+含量降低,尿量有所减少.结论:芫花与甘草反药组合导致机体电解质、AVP、ALD水平变化,提示两药合用可能会引起水盐代谢平衡失调,是其配伍禁忌的可能机制之一.
  • 摘要：Scoiopendra subspinipes mutiians L.Koch has been used for cancertreatment in traditional Chinese medicine for hundreds of years.In this study,the effects of a polysaccharide-protein complex from Scoiopendra subspinipes mutiiansL.Koch(SPPC) on the tumor growth and immune function were assessed in sarcoma S180 and hepatoma H22 bearing mice.Results showed that SPPC significantly inhibited the growth of S180 transplanted in mice and prolonged the survival time of H22-bearing mice.In S180-bearing mice,it promoted specific and nonspecific immune response as evidenced by enhancing the activities of natural killer(NK) cells,cytotoxic T lymphocytes(CTL) and the ratio of Thl/Th2 cytokines,and increasing the percentages of CD4+T cells,B cells and NK cells.Furthermore,SPPC not only significantly inhibited mRNA expression and production of the immunosuppressive cytokines(IL-10 and TGF-β),but also diminished arachidonic acid(AA)-metabolizing enzymes(COX-2 and CYP4A) and their products(PGE2 and20-HETE) in tumor-associated macrophages(TAMs).Taken together,our results indicate that SPPC inhibits tumor growth in vivo by improving antitumor immuneresponses at least partly via downregulating AA-metabolic pathways in TAMs,andcould act as an anti-tumor agent with immunomodulatory activity.
  • 摘要：The aim of the present study was to investigate the mechanisms of penetration enhancement by the Z.bungeanum oil(essential oil from Zanthoxylum bungeanum Maxim.) and to evaluate cytotoxicity of the essential oil.The cytotoxicity of the Z.bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using CCK-8 assay.The phase behavior and secondary structure changes of rat stratum corneum (SC) were measured by Differential Scanning Calorimetry(DSC) and Attenuated Total Reflection-Fourier Transform Infrared(ATR-FTIR),respectively.Molecular modeling was undertaken to further study the interactions of the Z.bungeanum oil with the SC lipid.Moreover,HaCaT cell lines were employed as the cell model to monitor the effect of the Z.bungeanum oil on keratinocytes.It was found that the Z.bungeanum oil appeared to be low skin toxicity in comparison to the well-established penetration enhancer Azone,and effectively alter the SC lipids and keratin to decrease the barrier properties of the skin.In addition,the Z.bungeanum oil could interact with ceramide 6 by forming hydrogen bonding to disrupt the ordered arrangement of the SC lipids,resulting in increased skin permeability.The Z.bungeanum oil could markedlyimprove HaCaT cell membrane fluidity and decrease cell membrane potential probably due to the increased intracellular Ca2+,perhaps leading tocertain changes in keratinocytes to alter the barrier properties of the skin.
  • 摘要：为了寻找活性更好的抗肿瘤化合物,以邻苯二胺和二羰基化合物为原料制备喹喔啉衍生物,并对所合成的吲哚并喹喔啉结构进行进一步衍生化,共合成19个喹喔啉衍生物,对合成的目标化合物经1H NMR,MS及元素分析进行了结构表征.以人肝癌细胞株HepG2和人肺癌细胞株A549为靶细胞,采用MTT法进行初步的体外抗肿瘤活性研究.结果表明,化合物8具有相对较好的抗肿瘤活性,2、3位苯基是抗肿瘤活性的增效官能团,吲哚并喹喔啉在低浓度并不表现出强的肿瘤细胞抑制作用.这为进一步研究喹喔啉抗肿瘤活性构效关系打下了基础.
  • 摘要：绝大部分实体瘤细胞能够通过异常的能量代谢和对特定蛋白的自身调节而使得其周围能够形成一个不适宜正常细胞生存的酸性的细胞外环境,这种酸性环境有利于肿瘤细胞的生长和转移.因此,本文通过静电纺丝方法将具有光谱抗肿瘤药物的羟基喜树碱(HCPT)携载到一种生物可降解的酸度敏感聚合物PBELA上,并作为瘤内植入制剂系统考察纤维抗肿瘤活性.瘤内植入纤维后,肿瘤生长缓慢,纤维植入14天后对肿瘤组织行HE染色显示载药纤维治疗组引起较多的肿瘤细胞坏死,免疫组化染色显示载药纤维治疗后能够引起较多的肿瘤细胞凋亡.
  • 摘要：建立乌头类双酯型生物碱生物转化前后的实时直接分析质谱检测方法.首次利用实时直接分析-线性离子阱串联质谱法(DART-IT/MSn)研究乌头碱(AC)、中乌头碱(MA)和次乌头碱(HA)在大鼠肠内菌中的代谢.代谢样品无需前处理,直接利用实时直接分析质谱离子源进行分析.在本实验中,对实时直接分析质谱离子源的重要实验参数进行优化,并以优化的DART- MSn方法对乌头类双酯型生物碱在大鼠肠内菌作用下的代谢产物进行结构确认及含量分析.每个样品分析时间少于1分钟.该方法检测结果与超高效液相色谱-质谱(UPLC-MS)分析结果具有很好的一致性.结果表明该方法准确、简便、快速,为实现药物代谢的高通量分析提供了一种强大的工具.
  • 摘要：目的:对不同产地中药海藻30种无机元素进行分析评价,阐明其分布特征.方法:样品经消解或灰化处理后,采用电感耦合等离子体-原子发射光谱法、碘离子选择性电极法分析了不同产地海藻药材的30种无机元素,并采用主成分综合评分法对不同产地海藻药材的品质进行评价.结果:不同产地海藻含有19-26种无机元素,平均含量按由高到低的顺序依次为K>Ca>Na>Mg.有害元素Cd、As和Al均超过《药用植物及制剂进出口绿色行业标准》和《食品添加剂使用卫生标准》的限量标准,部分样品Cu、Hg和Pb超标.海蒿子和羊栖菜中大部分元素含量无显著性差异.主成分综合评分法显示,山东烟台海蒿子样品H4、H3和浙江温州羊栖菜样品Y5、Y6综合排序较高,表明基于无机元素考虑这些产地的海藻样品品质较好.结论:海藻无机元素含量水平不仅受自身遗传因素的影响,也与药材产地等生态因素有关.实验数据可以为海藻药材的合理用药提供理论依据,同时为制订海藻有害元素限量标准和质量评价提供参考.
  • 摘要：FL/QD-TK在体外可以靶向叶酸受体高表达的肝癌Bel-7402细胞并且联合GCV表现出较强的选择性杀伤作用,而对肝癌受体低表达的HepG2细胞靶向和杀伤作用较差.FL/QDIK在体内可以对Bel-7402荷瘤裸鼠的肿瘤部位进行实时荧光成像,FL/QD-TK联合GCV在体内取得了良好的抗肿瘤作用,同时对各脏器组织形态学和血清学指标无影响.实验合成了新型叶酸靶向量子点标记自杀基因脂质体(FL/QD-TK),其可在体外靶向和选择性杀伤叶酸受体高表达肝癌细胞,在体内可视化示踪TK基因治疗并具备了较好的生物安全性,FL/QD-TK作为一种潜在的高效低毒的纳米药物有望应用于肝癌的诊治一体化.
  • 摘要：绝经后激素治疗与卵巢癌的发病风险存在一定关系,但相关研究结论存在争议.本文综合分析了近年来关于绝经后激素治疗与卵巢癌发病风险关系的文献,结果表明:使用激素治疗的绝经后妇女相比从未接受激素治疗者卵巢癌发病风险增加;随着激素治疗停药时间的延长,卵巢癌发病风险逐步降低;无论是单纯雌激素治疗还是雌孕激素联合治疗均会增加卵巢癌发病风险;且激素治疗的方案构成和给药途径对卵巢癌发病风险无影响.本文还对激素治疗与卵巢癌不同病理类型之间的关系进行了讨论.
  • 摘要：目的:筛选具有抗MRSA活性的中药,对其抗菌成分进行分离提纯,进行体外生物学活性进行系统评价.方法:对78种中药提取物进行PBP2a亲和力考察,筛选抗MRSA药材;醇水回流、石油醚、乙酸乙酯、正丁醇萃取初步处理药材,鉴定抗MRSA部位,柱层析进一步分离纯化,通过紫外、质谱、核磁共振对所得组分进行结构鉴定;通过该组分对MRSA252及36株MRSA临床分离株的MIC、MBC实验、对MRSA252的持续抑制作用及对菌体形态学影响实验,系统评价其体外生物学活性.结果:虎杖提取物与PBP2a具有最强亲和力,RU=624.69;虎杖乙酸乙酯层萃取产物经过分离纯化获得抗MRSA组分大黄素;大黄素对MRSA标准株及临床分离株的MIC为2～8μg/mL,MBC为4～32μg/mL,能够发挥持续抑菌作用,对细菌细胞壁产生明显影响,促进胞浆破裂.结论:大黄素具有较好的体外抗MRSA活性,具有进一步开展体内生物学活性及抗菌机制研究的重要意义.
  • 摘要：目的:研究加味五子衍宗方(MWP)及其活性部位对脂多糖诱导的BV-2小胶质细胞炎症反应的抑制作用及潜在机制.方法:MWP70%乙醇提取液通过大孔树脂柱分离,得水洗脱组、20%醇洗脱组、50%醇洗脱组、70%醇洗脱组和95%醇洗脱组5个部位,分析各部位总黄酮总多糖的含量.针对全药和无细胞毒性的活性部位研究其对炎症因子NO和炎症相关蛋白(NOS,COX-2)表达,对炎症转录因子NF-KB的激活,NADPH氧化酶活性以及对ROS表达的调控作用.结果:70%醇洗脱组和95%醇洗脱组有毒性,MWP和其余各部位f水洗脱组,20%醇洗脱组,50%醇洗脱组)均无毒性且表现出一定的抗炎活性.其中50%醇洗脱组抗炎活性最优,甚至高于MWP.MWP及其活性部位的抗炎活性主要表现在可以降低NO释放,抑制NOS、COX-2蛋白的表达,NF-KB的核转位,NADPH氧化酶活性和ROS的产生.结论:MWP可有效抑制LPS诱导的BV-2小胶质细胞炎症反应,其抗炎活性部位可能主要富集于50%醇洗脱部分,其抗炎活性可能是通过抑制NF-KB信号通路介导的炎症反应以及抗氧化应激实现的.
  • 摘要：通过观察温心方对动脉粥样硬化模型大鼠血脂、动脉粥样硬化指数(AI)、血清内皮素(ET-1)、一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)以及胸主动脉血管平滑肌组织(VSM) iNOS的表达,揭示温心方对血管内皮保护机制.实验选取5周龄雄性Wistar大鼠共85只.共分为6组,其中空白组10只作为对照,模型组、温心方(高、中、低)组、阿托伐他汀组各15只.造模方法为随机选取的75只大鼠腹腔注射维生素D3配合高脂喂养诱导150d.各治疗组采用灌胃法给药,对照组给予等量蒸馏水,治疗30d.生化检测血脂、ELISA法检测血清ET1.NO、AngⅡ,Western Blot和realtime PCR分别检测血管平滑肌iNOS蛋白及基因表达.结果,与对照组相比,各治疗组均能显著降低血脂及AI,同时能显著降低血清中ET—l和AngⅡ的含量、并升高NO含量,其中以温心方高、中剂量组和阿托伐他汀钙组作用最明显,并能在蛋白和基因水平显著降低VSM iNOS的表达.因此,温心方可通过减低动脉粥样硬化大鼠模型ET1、AngⅡ含量,升高NO含量,降低胸主动脉组织iNOS的表达,达到治疗动脉粥样硬化的作用.
  • 摘要：目的:研究湖北麦冬多糖对糖尿病肾病的保护作用和作用机制,为湖北麦冬多糖的进一步研究开发提供参考.方法:采用小剂量链脲佐菌素(STZ)加高脂高糖饲料诱导的糖尿病大鼠模型对湖北麦冬多糖高、中、低三个剂量组进行活性和机制研究.结果:湖北麦冬多糖能显著降低糖尿病大鼠的空腹血糖值(FBG)和糖化血红蛋白值(HbAlc),并且能显著改善糖尿病大鼠的葡萄糖耐量(OGTT).同时,湖北麦冬多糖能改善糖尿病大鼠血脂环境,降低氧化应激,改善肾脏功能参数,抑制肾脏结构病理变化,下调晚期糖基化终末产物(AGE)一晚期糖基化终末产物受体(RAGE)系统的表达.结论:湖北麦冬多糖具有降血糖和早期糖尿病肾病保护作用.
  • 摘要：目的:探讨含笑内酯对类风湿关节炎DBA/1小鼠模型的治疗作用.方法:将40只6周龄雄性DBA/1小鼠随机分为4组,空白对照组Nor(不作任何处理),模型对照组Con(诱导发病并腹腔注射DMSO),甲氨喋呤治疗组MTX(诱导发病并腹腔注射甲氨喋呤),实验组MCL(诱导发病并腹腔注射含笑内酯),用牛Ⅱ型胶原法诱导MTX、Con和MCL组小鼠发病建立类风湿关节炎模型;在二次免疫注射24小时后开始隔天腹腔注射给药并对小鼠体重和关节炎发病情况进行隔天观察,给药28次后停止给药,继续观察4次,眼球取血、蛋白芯片测血清中细胞因子,处死小鼠取爪子及膝盖骨做组织病理学检查.结果:成功构建了DBA/I小鼠类风湿关节炎模型;体重观察结果显示各组小鼠之间无明显差异;关节炎评分结果显示MCL组小鼠关节炎评分低于Con组(P

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