反义寡脱氧核苷酸

摘要： 为了研究c-jun调节hCG诱导仔猪睾丸间质细胞睾酮分泌的作用机制,采用离体仔猪睾丸间质细胞体外孵育法,c-jun ASODNs拮抗c-jun,加用cAMP,通过酶联免疫方法检测睾酮水平来观察c-jun在调节hCG诱导仔猪睾丸间质细胞分泌睾酮的影响.结果是hCG可刺激仔猪睾丸间质细胞的睾酮分泌,c-jun ASODNs(0.125～2 μmol/L)呈剂量依赖性抑制hCG诱导离体睾丸间质细胞的分泌(r=--0.787,P＜0.01).加用cAMP后睾酮分泌增加,可逆转c-jun ASODNs抑制hCG诱导离体睾丸间质细胞的睾酮分泌.结论是c-jun可促进hCG诱导离体仔猪睾酮间质细胞睾酮的分泌,此过程可能以cAMP作为第二信使,进行信息传递.

摘要： 研究放射性核素铼(188Re)标记脑胶质瘤U87-EGFRvⅢ(Epidermal Growth Factor Receptor Variant Ⅲ)细胞反义寡核苷酸序列的制备方法,探讨其作为脑胶质瘤反义显像剂的可能性.采用细胞指数富集的配基系统进化技术(Cell-based Systematic Evolution of Ligands by Exponential Enrichment,Cell-SELEX)筛选脑胶质瘤U87-EGFRvⅢ细胞,得到一段高亲和力的反义寡核苷酸序列U2,然后采用直接标记法进行188Re的放射性标记,按照正交实验设计进行188Re最佳标记条件的摸索,纸层析法测定标记率,通过体外稳定性实验评价188Re-U2的放化特性,测定标记物静脉注射后在大耳兔不同时相血液放射性清除曲线,应用SPECT显像观察标记物在兔体内的放射性动态分布变化.结果表明:在最佳标记条件下188Re-U2的标记率为70％±14％;经Sep-PaK C18反相柱分离纯化后,188Re-U2在生理盐水和血清中37°C下放置24h的放化纯度分别为70.6％和95.55％;188Re-U2在兔体内的血放射性清除迅速,主要通过肾脏排泄,其余脏器内放射性均较低.188Re直接法标记U87-EGFRvⅢ细胞反义寡核苷酸U2的方法简单,具有良好的标记率和体内外稳定性,并且体内分布动力学特性也比较理想.

摘要： Objective To explore the effects of the magnetic c-erbB-2 antisense probe on morphology and proliferation of SK-Br3 cancer cells at different transfection time points. Methods Breast cancer SK-Br3 cells were transfected with magnetic c-erbB-2 antisense probes containing 25 μg/mL iron and co-cultured for 6,12,24,36 and 48 h,respectively. The distribution and content of iron particles in SK-Br3 cells were determined by Prussian blue staining, electron microscopy and atomic absorption spectrometry respectively. Cell viability was observed by trypan-blue exclusion and CCK-8 assay. The protein expression of c-erbB-2 was detected by using Western blot. The signal intensity was measured by MR imaging. Results c-erbB-2 antisense probe was absorbed by SK-Br3 cells in a time-dependent manner within a range of time (6,12,24 h). When the incubation time was 24 h,the iron content in cells was (18. 38 + 0. 28) pg,the cell vitality and c-erbB-2 protein expression were reduced significantly (P0. 05). Conclusion The magnetic c-erbB-2 antisense probe can be effectively transfected into SK-Br3 cells and markedly inhibit the c-erbB-2 expression 24 h after transfection.%目的 探讨磁性c-erbB-2反义探针转染SK-Br3细胞株后,在不同时间点对其形态及表达的影响.方法 选择磁性c-erbB-2反义探针的含铁终浓度为25 μg/mL,分别孵育SK-Br3细胞6、12、24、36及48 h.采用普鲁士蓝染色并在光学显微镜及透射电镜下直接观察细胞铁颗粒,用原子吸收光谱法测定细胞内铁含量,锥虫蓝排除实验、CCK8实验观察细胞活性,Western blot检测蛋白质表达,MR成像研究信号强度的变化.结果 SK-Br3细胞在一定范围内(6、12、24 h)按时间依赖性摄取磁性c-erbB-2反义探针,当孵育时间为24 h时,细胞内铁含量为(18.38±0.28)pg,细胞活力、存活率及细胞内c-erbB-2蛋白表达量明显降低(均P＜0.05),MR成像显示细胞T2信号强度明显降低(P＜0.05).36 h及48 h组各项观察结果 与24 h组比较,差异均无统计学意义(均P＞0.05).结论 磁性 c-erbB-2反义探针转染SK-Br3肿瘤细胞24 h时,MR成像可以达到最佳显示且明显抑制c-erbB-2癌基因表达.

摘要： 目的 探讨不同质量浓度磁性c-erbB-2反义探针转染乳腺癌SK-Br-3细胞株后,对其形态及表达的影响.方法将反义探针含铁质量浓度分别定为5、10、25、50、100 mg/L,转染乳腺癌SK-Br-3细胞24 h.采用普鲁士蓝染色并在光学显微镜及透射电镜下直接观察细胞铁颗粒,原子吸收光谱法测定细胞内铁含量,台盼蓝排除实验、CCK-8试剂盒观察细胞活性,Western blot法检测蛋白质表达,磁共振成像研究信号强度的变化.结果 SK-Br-3细胞对反义探针在一定质量浓度范围内(5、10、25 mg/L)呈依赖式摄取.当探针质量浓度为25 mg/L时,细胞内铁含量为(18.38±0.28) pg,细胞活力、存活率及细胞内c-erbB-2蛋白表达量明显降低(P均＜0.05),磁共振扫描图像显示该组细胞T2值出现明显降低(P＜0.05).50及100 mg/L组各项结果与25 mg/L组比较差异无统计学意义(P均＞0.05).结论 当磁性c-erbB-2反义探针质量浓度为25 mg/L时,可有效转染并特异性抑制SK-Br-3细胞株的表达,并被磁共振成像所检测.%Objective To explore the effects of the magnetic c-erbB-2 antisense probe of different concentrations on the morphology and expression of SK-Br-3 cancer cells in vitro. Methods Breast cancer SK-Br-3 cells were transfected for 24 h by antisense probe at an iron concentration of 5, 10, 25, 50, and 100 mg/L, respectively. The distribution and content of iron particles in SK-Br-3 cells was determined by Prussian blue staining, electron microscopy, and atomic absorption spectrometry. Cell viability was observed by trypan-blue exclusion and CCK-8 test. The protein expression of c-erbB-2 was assessed by the Western blot analysis. The changes of the signal strength were considered by magnetic resonance imaging ( MRI). Results c-erbB-2 anti-sense probe was uptake by SK-Br-3 cells in a concentration-dependence manner within a certain range (5 , 10,25 mg/L). When the probe concentration was 25 mg/L, iron content in cells was (18. 38 ±0. 28) pg, the cell vitality, survival, and c-erbB-2 protein expression were reduced significantly (all P 0. 05). Conclusion The magnetic c-erbB-2 antisense probe can effectively transfect and specifically inhibit the expression of SK-Br-3 cell lines at the iron concentration of 25 mg/L.

摘要： 目的 观察血管内皮生长因子(vascular endothelial growth factor,VEGF)反义寡脱氧核苷酸(ASODN)联合血管生成素-1(angiogenin-1,Ang-1)对糖尿病视网膜病变(diabetic retinopathy,DR)大鼠视网膜血管渗漏及新生血管生成的影响.方法 选取健康雄性SD大鼠60只,随机分为正常对照组(A组)5只和糖尿病组55只,糖尿病组通过链脲佐菌素腹腔注射诱导糖尿病模型成功后再饲养3个月行眼底荧光血管造影检查,确定DR大鼠模型且视网膜病变程度相仿的大鼠,随机抽取45只分为DR对照组(B组,5只)、PBS缓冲液对照组(C组,10只)、VEGF ASODN干预组(D组,10只)、Ang-1干预组(E组,10只)、联合干预组(F组,10只).C组玻璃体内注射PBS缓冲液5μL;D组玻璃体内注射浓度为100 μmol·L-1 VEGF ASODN 5 μL;E组玻璃体内注射浓度为160 mg·L-1Ang-1 5 μL;F组玻璃体内注射100 μmol·L-1 VEGF ASODN及160 mg·L-1 Ang-1各5μL;3 d后再次行上述操作.各组大鼠行眼底荧光血管造影检查,对比观察不同组别大鼠视网膜血管渗漏情况,病理组织切片光学显微镜下突破内界膜的观察视网膜新生血管芽细胞核数.结果 A、B、C、D、E和F组视网膜新生血管渗漏面积分别为0、( 20.98±1.14) mm2、(21.47±1.65) mm2、(14.60±1.55) mm2、(13.80 ±1.19) mm2、( 10.81±1.35) mm2;D、E、F组新生血管渗漏面积低于B、C组,差异有统计学意义(F=103.99,P ＜0.05)；F组渗漏面积低于D、E组,差异有统计学意义(F=190.94,P＜0.05);B组与C组之间差异无统计学意义(t =0.22,P＞0.05).A、B、C、D、E和F组突破内界膜的新生血管芽细胞核数分别为(1.13±0.31)个、(80.31±5.21)个、(81.08 ±2.57)个、(37.37±3.41)个、(41.07±2.09)个、(14.41±1.23)个；D、E、F组突破内界膜的血管芽细胞核数均低于B、C组,差异有统计学意义(F=1339.41,P＜0.05)；F组突破内界膜的血管芽细胞核数低于D、E组,差异有统计学意义(F =714.91,P ＜0.05)；B组与C组之间差异无统计学意义(t=0.35,P＞0.05).结论 VEGFASODN联合Ang-1玻璃体内注射能明显抑DR大鼠视网膜新生血管的生成,减少视网膜血管渗漏.

摘要： 目的:探讨磁性c-erbB2反义寡脱氧核苷酸探针对SK-Br-3肿瘤细胞株形态及表达的影响,阐明该探针是否同时具有诊断与治疗功能.方法:磁性c-erbB2反义探针转染高表达c-erbB2的SK Br 3肿瘤细胞作为实验组,磁性c-erbB2反义探针转染Fuda肿瘤细胞株、SPIO及ASODN转染SK-Br-3肿瘤细胞、未转染的SK-Br-3肿瘤细胞设置为4个对照组,普鲁士蓝染色光镜观察细胞内铁的分布,透射电镜观察其超微结构,并检测细胞cerbB2蛋白表达变化及铁含量,行体外MR成像.结果:光镜显示SK-Br-3肿瘤细胞胞浆内散在分布铁颗粒,透射电镜观察到SK-Br-3肿瘤细胞胞浆内铁颗粒、团状吞饮体,细胞出现胞膜空泡化、细胞固缩、核固缩及凋亡小体,而对照组细胞无上述改变；与对照组比较,实验组SK-Br3细胞蛋白的表达抑制率明显升高,细胞铁含量增加(P＜0.01),MR扫描显示信号减低(P＜0.05).结论:磁性c-erbB2反义探针能够顺利进入SK-Br-3肿瘤细胞,不仅能导致SK-Br-3细胞的凋亡,还能够被体外MR成像所检测,可能成为一种具有治疗与诊断意义的双功能探针.

摘要： 目的 研究聚酰胺-胺型树枝状高聚物(PAMAM-D)纳米载体介导组织因子(TF)反义寡脱氧核苷酸防治大鼠心肌缺血再灌注损伤的分子机制.方法 分别设计合成针对大鼠TF的反义寡脱氧核苷酸(AS/TF)、正义寡脱氧核苷酸(S/TF)和错配寡脱氧核苷酸(Sc/TF),分别耦联于PAMAM-D纳米载体,构建ODN-PAMAM-D的聚合物.将100只雄性Lewis大鼠随机等分为假手术组、缺血再灌注组、AS/TF防治组、S/TF对照组和Sc/TF对照组.除假手术组和缺血再灌注组大鼠静脉分别注入生理盐水和PAMAM-D外,其余3组大鼠分别注入与PAMAM-D相耦联的相应寡核苷酸.各组大鼠于注射后10 h开胸暴露心脏,除假手术组以外的其他4组大鼠于冠状动脉左前降支中1/2处结扎造成心肌缺血.心肌缺血90 min后,解除结扎,再灌注3 h.假手术组的大鼠于冠状动脉左前降支中1/2处只穿线,不结扎,持续4 h 30 min.分别于缺血90 min和再灌注结束后取各组大鼠的血液检测肌钙蛋白T(TnT)和乳酸脱氢酶(LDH)的含量.并于实验结束后取梗死区及边缘区心肌组织检测TF基因的转录、TF的促凝活性(TF∶C)和TF的抗原含量(TF∶Ag)以及活性氧簇(ROS)、蛋白酶激活受体-1(PAR-1)和p38 有丝分裂原激活蛋白激酶(p38 MAPK)的表达.结果 心肌缺血90 min及再灌注3 h后,缺血再灌注组大鼠血液中的TnT和LDH含量均显著高于假手术组,而AS/TF防治组均明显低于其他3个缺血再灌注组(P<0.05);梗死区及边缘区心肌组织中TF基因的转录和表达均强于假手术组,AS/TF防治组则较其他3个缺血再灌注组明显减弱(P<0.01).流式细胞学检测显示,心肌缺血再灌注3 h后,各缺血再灌注组大鼠心肌组织中ROS、PAR-1和p38 MAPK的表达均显著增多,AS/TF防治组则明显低于缺血再灌注组、S/TF对照组和Sc/TF对照组(P<0.05).结论 TF不仅介导了凝血过程,而且通过激活PAR-1和p38 MAPK诱发了炎性反应,从而加重了心肌组织损伤.TF是心肌缺血再灌注损伤的"中心分子",针对TF的反义寡脱氧核苷酸耦联G10代PAMAM-D纳米载体不仅抑制了TF的转录和表达,而且减轻了心肌缺血再灌注损伤.%Objective To investigate the possible mechanism of polyamidoamine dendrimers( PAMAM-D ) mediated antisense oligodeoxynucleotide against tissue factor ( TF ) improving myocardial ischemia reperfusion injury. Methods Anti-sense oligodeoxynucleotide ( AS/TF ), sense oligodeoxynucleotide ( S/TF ) and scrambled oligodeoxynucleotide against TF ( Sc/TF ) were designed and synthesized respectively, and then were coupled with PAMAM-D nanometer vector to establish ODN PAMAM D polymers. 100 male Lewis rats were randomly divided into sham operation group, ischemia reperfusion group, AS/TF intervention group, S/TF control group and Sc/TF control group. Besides rats in sham operation group and ischemia reperfusion group were administrated with natural solution and PAMAM-D respectively, rats in other three groups received corresponding oligodeoxynucleotide coupled with PAMAM-D. 10 hours after injection, the chest of each rat was opened with the heart exposed except from those in sham operation group, rats in other 4 groups underwent myocardial ischemia reperfusion by ligaturing left anterior descending coronary artery for 90 min and removing the ligation for 3 hours. In sham operation group, only a thread was put under the left anterior descending coronary artery of each rat, and no ligation was performed and lasted for 4 hours and 30 min. Blood sample was collected after 90 min of ischemia and the end of reperfusion respectively for the concentrations of troponin T ( TnT ) and lactate dehydrogenase ( LDH ) determination. At the end of reperfusion, myocardial tissue in the infarct and ischemic area were collected for TF gene transcription detection, TF procoagulant activity ( TF: C ) determination and TF antigen ( TF: Ag ) assay. In addition, reactive oxygen species ( ROS ), protease activated receptor-l( PAR-1 ) and p38 mitogen activated protein kinase ( p38 MAPK ) were also determined. Results After 90 min of ischemia and the end of reperfusion, concentrations of TnT and LDH increased obviously, while those in AS/TF intervention group were much lower than in other three ischemia reperfusion injured groups( P ＜0. 05 ). At the end of reperfusion, the transcription and expression of TF gene in myocardial tissue of the infarct and ischemic area were more enhanced in ischemia reperfusion injured groups, however, they were improved in AS/TF intervention group than other three ischemia reperfusion groups( P ＜0.01 ). Flow cytometry showed that after 3 hour myocardial ischemia reperfusion, ROS, PAR-1 and p38 MAPK were expressed much higher in myocardial tissue, however, they were much lower in AS/TF intervention group than those in ischemia reperfusion group, S/TF control group and Sc/TF control group( P ＜0.05 ). Conclusion TF aggravates myocardial ischemia reperfusion injury by mediating blood coagulation process and inducing inflammation by means of activating PAR-1 and p38 MAPK respectively. Therefore, TF is the "central molecule" in myocardial ischemia reperfusion injury. Polyamidoamine dendrimers nanometer vector mediated antisense oligodeoxynucleotide against tissue factor not only inhibits the transcription and expression of TF, but also improves myocardial ischemia reperfusion injury.

摘要： 目的:探讨反义寡脱氧核苷酸(ASODN)抑制多药耐药基因(mdr1)对耐阿霉素(ADM)肝癌细胞HepG2/ADM化疗敏感性的影响.方法:以多药耐药基因mdr1人工合成寡脱氧核苷酸(ODN),其中ODN分为ASODN和正义寡脱氧核苷酸(SODN),并采用脂质体转染技术将ODN与HepG2/ADM共培养,试验分为反义寡脱氧核苷酸(mdr1-ASODN)处理组、正义寡脱氧核苷酸(mdr1-SODN)对照组和空白对照组,通过逆转录聚合酶链式反应和蛋白免疫印迹法观察HepG2/ADM细胞中mdr1mRNA及其蛋白表达情况；MTT法观察HepG2/ADM细胞转染mdr1-ASODN前、后对化疗药物(ADM、顺铂、5-氟尿嘧啶)的敏感性.结果:与mdr1-SODN对照组和空白对照组比较,mdr1-ASODN处理组HepG2/AMD细胞中mdr1mRNA及其蛋白表达均明显降低(P＜0.05)；与转染前比较,HepG2/ADM细胞的增殖抑制率明显增加(P＜0.05).结论:ASODN能有效抑制mdr1基因表达,并恢复肝癌HepG2/ADM细胞对化疗药物的敏感性.%OBJECTIVE: To investigate the effects on chemosensitivity of adriamycin (ADM)-resistant hepatoma carcinoma cells (HepG2/ADM) by inhibition of multidrug resistance 1 (mdri) expression with antisense oligodeoxyribonucleotide (ASODN). METHODS: Oligodeoxyribonucleotide (ODN) of mdr! Gene was synthesized and included ASODN and SODN, then transfected into HepG2/ADM hepatoma carcinoma cells by liposome transfection reagent. HepG2/ADM hepatoma carcinoma cells were divided into mdrrASODN treatment group, mdr,-SODN control group and blank control group. RT-PCR and Western blotting were used to detect their mRNA and protein expressions of mdri. The sensitivity of HepG2/ADM cells before and after transfected by mdr.-ASODN to chemotherapeutic drugs (ADM, cisplatin, 5-fluorouracil) was evaluated by MTT assay. RESULTS: Compared with mdri-SODN control group and blank control group, the mRNA and protein expressions of mdri were significantly decreased in mdri-ASODN treatment group (P<0.05); compared with before transfection, the inhibitory effects of chemotherapeutic agents on the proliferation of HepG2/ADM hepatoma carcinoma cells were increased in vitro (P<0.05). CONCLUSION: ASODN inhibits the expressions of mdri and enhances the sensitivity of HepG2/ADM cells to chemotherapeutic agents in vitro.

摘要： 目的 探讨超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)标记的c-erbB2反义寡脱氧核苷酸探针在新西兰大白兔及BALB/c小鼠体内的药动学及主要脏器分布.方法 18只新西兰大白兔随机分为高、中、低剂量3组,选择注射前30 min、注射后1、3、5、10、20、40、60、120、180、360、720 min等时间点,从对侧耳缘静脉采血,测定铁含量以了解探针的药动学；BALB/c小鼠60只随机分为MR扫描组及取脏器组,在注射反义探针后10、30、60、180、360 min这5个时间点,同步进行MR扫描及取肝、脾、心、肾、肌肉标本,测定观察脏器的信噪比及铁含量,观察反义探针在BALB/c小鼠的主要脏器分布.结果 高、中、低剂量的反义探针注射后的药动学符合二室模型,半衰期长；反义探针在脾脏富集量最高,以下依次为肝脏、肌肉、心脏及肾脏.结论了解反义探针在活体内的药动学及主要脏器分布,可以为进一步的活体MR成像时间及剂量选择等提供依据.%OBJECTIVE To investigate the pharmacokinetic parameters and main organ distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in new Zealand white rabbits and BALB/c mice. METHODS Eighteen new Zealand white rabbits randomly divided into high, middle and small dose groups. Blood was taken to measure iron content from offside ear edge vein 30 min before and 1,3,5, 10, 20, 40, 60, 120, 180, 360 and 720 min after injection. The pharmacokinetic parameters were calculated. 60 BALB/c mice were randomly divided into MR scan and organ extract groups. Synchronous MR scan and ertout of liver, spleen, heart, kidney and muscle were carried out 10, 30, 60, 180 and 360 min after injection, the signal-noise ratio and organ iron content were measured to find out the organ distribution. RESULTS The pharmacokinetics of high, middle and small dose antisense probe complied with two-compartment model with long half-life. The highest concentration was found in spleen; followed by liver, muscle, heart and kidney. CONCLUSION This study has found out the pharmacokinetic parameters and main organ distribution of antisense probe, which provides basis for the time and dose of in vivo MR imaging.

摘要： 目的 研究聚酰胺-胺型树枝状高聚物(PAMAM-D)纳米载体介导组织因子(TF)反义寡脱氧核苷酸防治大鼠心肌缺血再灌注损伤的分子机制.方法 将100只雄性Lewis大鼠随机等分为5组.除假手术组和缺血再灌注组大鼠静脉分别注入0.9%氯化钠溶液和PAMAM-D外,其余3组分别注入与PAMAM-D相藕联的相应寡核苷酸.分别于缺血90 min和再灌注结束后取5组大鼠的血液检测肌钙蛋白T(TnT)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化酶(GSH-PX)的含量.将梗死区及边缘区心肌组织剪下,检测TF基因的转录;另分别检测TF的促凝活性(TF:C)和采用检测TF的抗原含量(TF:Ag).结果 假手术组和其余4组大鼠血液中的TnT、LDH、MDA、SOD和GSH-PX的含量比较,差异有统计学意义(P<0.05或<0.01);而AS/TF防治组与其他3个缺血再灌注组比较,差异有统计学意义(P<0.05或<0.01).假手术组梗死区及边缘区心肌组织中TF基因的转录和表达均弱于其他4组(P<0.01),而AS/TF防治组则较其他3个缺血再灌注组明显减弱(P<0.01).结论 PAMAM-D纳米载体介导的TF AODN通过拮抗组织因子,抑制心肌缺血再灌注过程中的脂质过氧化损伤,对心肌缺血再灌注损伤有明显的保护作用.%Objective To investigate the possible mechanism of polyamidoamine dendrimers (PAMAM-D) mediated antisense oligodeoxynucleotide against tissue factor (TF) in improving myocardial ischemia-reperfusion injury in rats. Methods The 100 male Lewis rats were randomly divided into 5 groups.Except for the rats in sham operation group and ischemia-reperfusion group who were administrated with natural solution and PAMAM-D respectively, the rats in the other three groups received corresponding oligodeoxynucleotide coupled with PAMAM-D. The blood samples were collected at the 90th min of ischemia and the end of reperfusion respectively, and the concentrations of troponin T (TnT), lactate dehydrogenase ( LDH ), malondialdehyde (MDA),superoxide dismutase(SOD) and glutathione peroxidase (GSH-PX) were detected. Myocardial tissues in the infarct and ischemic zone were collected for TF procoagulant activity (TF:C) determination and TF antigen (TF:Ag). Results The concentrations of TnT, LDH, MDA, SOD and GSH-PX were significantly different as compared with those in sham operation group ( P＜0.05 or＜0.01 ) ,however, which in AS/TF intervention group were significantly different as compared with those in the other 3 ischemia -reperfusion injure groups( P＜0.05 or ＜0.01 ). The transcription and expression of TF gene in myocardial tissue of the infarct and ischemic zone were significantly increased in ischemia-reperfusion injure groups ,as compared with those in sham operation group( P＜0.05 or ＜0.01 ), however,which were obviously improved in AS/TF intervention group,as compared with those in the other 3 ischemia-reperfusion injury groups ( P＜ 0.01 ). Conclusion The PAMAM-D mediated TF AODN can relieve the peroxidative injury caused by myocardial ischemia-reperfusion, which has obvious protective effect on myocardial ischemia-reperfusion injury by inhibiting the transcription and expression of TF.

摘要： 目的和方法：用离体细胞体外孵育法，观察c-fos、c-myb和c-erbB-2反义寡脱氧核苷酸(c-fosODN、c-mybODN和c-erbB-2ODN)对hCG诱导大鼠颗粒细胞孕酮产生的影响，同时观察内皮素-1、γ-氨基丁酸和钙离子通道阻断剂维拉帕米对颗粒细胞中c-fos、c-myb和c-erbB-2蛋白的影响。结果：反义c-fos、c-myb和c-erbB-2ODN均明显抑制hCG诱导颗粒细胞孕酮的产生，并伴有各自癌基因蛋白染色阳性的颗粒细胞百分率下降；而无义tatODN没有相应的作用。2×10-7mol/L内皮素-1和5×10-6mol/Lγ-氨基丁酸能显著抑制hCG诱导颗粒细胞孕酮的产生，同时使c-fos、c-myb和c-erbB-2蛋白染色阳性的颗粒细胞百分率下降；而1×10-mol/L维拉帕米对hCG诱导颗粒细胞孕酮的产生和c-fos、e-myb和C-erbB-2蛋白染色阳性的颗粒细胞百分率均无明显影响。rn 结论：c-fos、c-myb和c-erbB-2与hCG诱导颗粒细胞孕酮的产生密切相关；内皮素-1，γ-氨基丁酸能通过调节这些癌基因在颗粒细胞中的表达而影响hCG诱导颗粒细胞孕酮的产生；而Ca2+无相应的作用。

摘要： 涉及一种核苷酸，尤其是一种抑制人体恶性肿瘤细胞生长的Bcl-2反义硫代磷酸寡脱氧核苷酸抗癌药物及其制备方法与用途。所说的Bcl-2反义硫代磷酸寡脱氧核苷酸的DNA序列为5’-TCCCAGCGTGCGCCATCC-3’。能特异性地与肿瘤细胞Bcl-2mRNA以碱基互补结合，封闭其表达，从而促进肿瘤细胞凋亡，抑制肿瘤细胞生长，达到抗癌治癌的目的。

摘要： 在这里公开一种CpG寡脱氧核苷酸(CpG‑ODN)，其是作为开发用于在不同物种中使用作为佐剂的有效免疫刺激。TLR9为CpG‑ODN的细胞受体，且目前开发的CpG‑ODN对兔子的TLR9具有低活性。本文中，包含约11‑14个脱氧核苷酸的GACGTT或AACGTT基序的CpG‑ODN类型展现出对兔子的TLR9具有有效的免疫刺激活性，且能够在兔子中提升较少毒性且有效的抗体反应。

摘要： 本发明提供一种CpG寡脱氧核苷酸(CpG‑ODN)，CpG‑ODN包含一个或多个重复的GTCGTT序列、一个或多个重复的GTT序列、以及一个或多个重复的TTTT序列，其中至少一个重复的GTCGTT序列是编码在GTT序列及TTTT序列之间。本发明还包含CpG‑ODN的免疫组成物及其在制备治疗或预防宿主疾病的免疫反应的药物用途。

摘要： 本公开涉及一种包括硫代磷酸化寡脱氧核苷酸(ODN)序列缀合于短活化RNA(saRNA)或反义寡核苷酸序列(ASO)的经分离化合物、这种化合物的组合物、以及通过一种所公开化合物或组合物来达成的治疗癌症和自体免疫疾病(伴有或不伴有刺激免疫应答)的方法、免疫刺激方法、使CEBPA活化的方法和使STAT转录因子的活性降低的方法。

摘要： 本发明提供寡脱氧核苷酸，其包含CpG寡脱氧核苷酸及能够与β‑1,3‑葡聚糖形成复合体的长度的聚脱氧腺苷酸，所述CpG寡脱氧核苷酸包含式(I)：5’X‑CpG‑L‑CpG‑TZ3’(I)(式中，X为T或C，L为由1～7个碱基形成的核苷酸序列，Z为T或C)表示的核苷酸序列且由8～16个碱基形成，聚脱氧腺苷酸与CpG寡脱氧核苷酸的3’侧连结。另外，本发明提供含有该寡脱氧核苷酸及β‑1,3‑葡聚糖的复合体。

摘要： 涉及一种核苷酸，尤其是一种抑制人体恶性肿瘤细胞生长的Bcl－2反义硫代磷酸寡脱氧核苷酸抗癌药物及其制备方法与用途。所说的Bcl－2反义硫代磷酸寡脱氧核苷酸的DNA序列为5’－TCCCAGCGTGCGCCATCC－3’。能特异性地与肿瘤细胞Bcl－2mRNA以碱基互补结合，封闭其表达，从而促进肿瘤细胞凋亡，抑制肿瘤细胞生长，达到抗癌治癌的目的。

摘要： 反义寡核苷酸(Antisense Oligonucletides)是一类具有抗病毒、抗癌等潜力的核酸类药物。应用重组质粒生产反义寡脱氧核糖核苷酸(即反义DNA)为反义核酸低成本大规模生产提供了一条开创性的方法。本发明大体可概括为将含反义寡核苷酸顺序的双链用内切酶的方法插入质粒中，待重组质粒扩增后，用内切酶切下含反义寡核苷酸顺序的双链，核酸酶S

摘要： 本公开涉及一种包括硫代磷酸化寡脱氧核苷酸(ODN)序列缀合于短活化RNA(saRNA)或反义寡核苷酸序列(ASO)的经分离化合物、这种化合物的组合物、以及通过一种所公开化合物或组合物来达成的治疗癌症和自体免疫疾病(伴有或不伴有刺激免疫应答)的方法、免疫刺激方法、使CEBPA活化的方法和使STAT转录因子的活性降低的方法。

摘要： 在这里公开一种CpG寡脱氧核苷酸(CpG‑ODN)，其是作为开发用于在不同物种中使用作为佐剂的有效免疫刺激。TLR9为CpG‑ODN的细胞受体，且目前开发的CpG‑ODN对兔子的TLR9具有低活性。本文中，包含约11‑14个脱氧核苷酸的GACGTT或AACGTT基序的CpG‑ODN类型展现出对兔子的TLR9具有有效的免疫刺激活性，且能够在兔子中提升较少毒性且有效的抗体反应。

摘要： 本发明公开了一种使用CpG寡脱氧核苷酸和β‑1，3‑葡聚糖的联合给药系统，属于癌症的免疫治疗领域，本发明抑瘤效果显著，较单独用药或以复合物的联合给药更能发挥CpG寡脱氧核苷酸和β‑1，3‑葡聚糖的联合抑瘤效果，尤其是提前注射β‑1，3‑葡聚糖比CpG寡脱氧核苷酸和β‑1，3‑葡聚糖一起给药抑瘤效果好。