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肝硬化,实验性

肝硬化,实验性的相关文献在1997年到2020年内共计72篇,主要集中在内科学、基础医学、医学研究方法 等领域,其中期刊论文72篇、专利文献563509篇;相关期刊33种,包括国际中医中药杂志、河北中医、医学临床研究等; 肝硬化,实验性的相关文献由328位作者贡献,包括刘平、张百萌、李坚等。

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肝硬化,实验性

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  • 刘平
  • 张百萌
  • 李坚
  • 丁继光
  • 付荣泉
  • 刘成海
  • 史文举
  • 吴樱樱
  • 吴金国
  • 吴锡铭
  • 期刊论文
  • 专利文献

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    • 李盛; 焦志勇; 饶佩斯; 钟燕明
    • 摘要: [目的]探讨人羊水干细胞移植对大鼠四氯化碳诱导性肝硬化的治疗作用及其机制.[方法]采用60%的四氯化碳植物油皮下注射7周制造肝硬化大鼠模型,再随机分成对照组(注射等体积PBS)、hAFSC移植组和hAFSC移植后基质细胞衍生因子Ⅰ(SDF-1)受体CXCR4的特异性阻断剂普乐沙福(AMD3100)干预组,处理3周后处死所有大鼠,检测大鼠血清碱性磷酸酶(ALP)、白蛋白(ALB)和胆固醇(Ch),按Ishak评分标准评估肝硬化情况.体外实验分为3个组:对照组(等剂量PBS)、AMD3100组、AMD3100+ SDF-1组,观察不同处理因素对hAFSC的存活、迁移、黏附的影响.[结果]与对照组比较,移植组的血清ALB和Ch均显著升高(P<0.05),ALP无显著变化(P>0.05),而干预组的ALP、ALB及Ch与对照组比较差异均无统计学意义(P>0.05).移植组与对照组肝组织纤维化评分比较差异有统计学意义(P=0.005),移植组与干预组也有显著差异(P=0.022).体外实验结果表明:SDF-1能缓解AMD3100对hAFSC的迁移、存活、黏附的抑制(P<0.05).[结论]hAFSC经静脉肝内移植可减轻大鼠四氯化碳诱导性肝硬化病变程度,其机制与SDF-1/CXCR4调控有关.
    • 王明; 李辉; 王静; 高嵩
    • 摘要: 目的:利用X射线衍射增强成像(diffraction enhance imaging,DEI)的空间高分辨率和高相位衬度特征,对小鼠肝纤维化样本进行成像,观察纤维化病变在DEI图像中的表象特征,并对正常肝组织及肝纤维化图像进行纹理特征分析,探讨量化诊断肝纤维化病变的有效性.方法:实验在北京同步辐射装置(Beijing Synchrotron Radiation Facility,BSRF)4W1A光束线形貌学实验站完成,样品为四氯化碳(carbon tetrachloride,CCl4)诱导的ICR小鼠肝纤维化模型及正常肝脏组织标本.对样品进行DEI成像后,对肝脏组织进行马松(Masson)染色,将DEI图像与病理结果进行比对,分析得到不同程度纤维化病变的影像学特征.基于灰度共生矩阵(gray level co-occurrence matrix,GLCM),计算DEI图像感兴趣区域(region of interest,ROI)的九种纹理特征参数,分析纹理特征参数与纤维化病变程度的相关性.结果:正常及不同程度的肝纤维化组织在DEI图像上差异明显,能量、熵、惯性矩、逆差距、差的熵以及差的均值六种纹理特征值能够明显区分不同程度肝纤维化(P<0.05),其中,熵、惯性矩、差的熵、差的均值随着肝纤维化程度的加重而增大,而能量、逆差距随着肝纤维化程度的加重而减小,熵的变化程度最为明显.结论:正常及不同程度的肝纤维化模型在DEI图像上差异明显,基于GLCM提取的图像纹理特征参数能够对不同程度的肝纤维化进行区分.DEI成像为肝纤维化的诊断提供了一种潜在的影像学途径.
    • 郭燕荣; 陈昕; 董常峰; 林浩铭; 张新宇; 温慧莹; 沈圆圆; 汪天富; 陈思平; 刘映霞
    • 摘要: Objective To evaluate the value of acoustic radiation force impulse (ARFI) elastography in assessment of nonalcoholic fatty liver disease (NAFLD) and hepatic fibrosis in rats.Methods Models with various degrees of NAFLD severity were conducted in 110 rats by feeding high fat emulsion.The right liver lobe of rat models were processed and embedded in a fabricated gelatin solution to measure the shear wave velocity (SWV) by ARFI.And the other liver lobes were used for histologic assessment.Based on NAFLD activity score (NAS),the final pathologic NAFLD diagnosis were considered as normal group (NAS=0),simple steatosis (SS) group (1≤NAS≤2),borderline (3≤NAS≤4) group and nonalcoholic steatohepatitis (NASH) group (NAS≥5).The diagnostic accuracy of the SWV parameters in evaluating NAFLD severity and fibrosis stages was studied using ROC curves.Results The difference of SWV values among normal group,SS group,borderline group and NASH group was statistically significant (F=31.53,P<0.001).Taking SWV≥ 2.54 m/s as the diagnostic standard to differentiate normal rats from rats with SS,and SWV≥2.90 m/s to differentiate SS from NASH in rats,the area under ROC curve (AUC) was 0.922 (95%CI [0.871,0.973],P<0.001) and 0.882 (95% CI [0.807,0.956],P<0.001) respectively.The sensitivity and specificity were 93.5 % and 100 % for differentiating normal and SS groups,83.3 % and 84.2 % for differentiating SS and NASH groups.Taking SWV≥3.48 m/s as cutoff to predict fibrosis (≥F2 stage),the AUC was 0.963 (95%CI [0.909,1.000],P<0.001),the sensitivity was 92.9% and the specificity was 97.6%.Taking SWV≥3.61 m/s as cutoff to predict severe fibrosis (≥F3 stage),the AUC was 0.997 (95%CI [0.990,1.000],P<0.001),sensitivity was 100% and specificity was 98.9%.The same high validity was maintained as in the prediction of cirrhosis (F4 stage) with the cutoff as SWV≥4.50 m/s,and the AUC was 0.993 (95%CI [0.982,1.000],P<0.001),the sensitivity was 100 % and the specificity was 96.8%.Conclusion ARFI elastography is a promising method for differentiating the different severity of NAFLD and staging the degree of hepatic fibrosis with NAFLD in rat models.%目的 探讨利用声辐射力脉冲成像(ARFI)技术评估大鼠肝脏非酒精性脂肪肝(NAFLD)及肝纤维化的价值.方法 通过喂养高脂食物建立不同阶段NAFLD大鼠模型.解剖大鼠,取右叶肝脏嵌入明胶仿体内用于ARFI检查,测量大鼠肝脏剪切波速度(SWV),将其余肝组织用于组织学评估,并根据NAFLD活动性评分(NAS),将大鼠分为正常组(NAS=0),单纯性脂肪肝(SS)组(1≤NAS≤2),边界组(3≤NAS≤4)、非酒精性脂肪性肝炎(NASH)组(NAS≥5).通过ROC曲线分析评估ARFI判断不同程度NAFLD及肝纤维化的能力.结果 正常组、SS组、边界组、NASH组间SWV值总体差异有统计学意义(F=31.53,P<0.001).以SWV值≥2.54 m/s鉴别正常组与SS组、以SWV值≥2.90 m/s鉴别SS组与NASH组,对应的ROC曲线下面积(AUC)分别为0.922[95% CI(0.871,0.973),P<0.001]、0.882[95% CI(0.807,0.956),P<0.001],敏感度分别为93.5%、83.3%,特异度分别为100%、84.2%.以SWV值≥3.48 m/s诊断≥F2期肝纤维化、以SWV值≥3.61 m/s诊断≥F3期肝纤维化、以SWV值≥4.50 m/s诊断肝硬化(F4期)的AUC分别为0.963[95%CI(0.909,1.000),P<0.001]、0.997[95%CI(0.990,1.000),P<0.001]、0.993[95%CI(0.982,1.000),P<0.001],敏感度分别为92.9%、100%、100%,特异度分别为97.6%、98.9%、96.8%.结论 ARFI技术测量的SWV值可有效评估NAFLD及含有NAFLD的肝纤维化程度.
    • 张迪; 张雅敏; 崔子林; 杨龙; 李阳
    • 摘要: Objective To explore a reliable method of 70% hepatectomy model in liver fibrosis mice. Methods Sixty-six C57BL6 mice were randomly devided into control group (n=6), the traditional group (n=30, ligation and removal liver lobe) and improved group (n=30, removal of liver lobe after blocking blood flow). Those 60 mice were induced liver fibrosis firstly, then randomly divided into six mice in each group, and were sacrificed at preoperative, 12, 24, 48 and 72 hours after liver resection. Liver tissues and blood samples were collected. The survival rate and incidence of complications were recorded and compared between two groups. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to observe the liver injury after 70%hepatectomy. The ratio of liver weight to body weight and the expression of proliferating cell nuclear antigen (PCNA) were also measured to observe the difference of liver regeneration between the two groups. Results (1) Compared to the pathological control group, liver fibrosis model was established successfully in both traditional group and improved group, which can be used in 70%hepatectomy. So the follow-up experiment can be undertook timely. (2) Compared to traditional group, the survival rate was improved significantly in improved group (96.67%vs. 73.33%), and the incidence of complications was significantly lower (P<0.05). (3) The ALT and AST levels were higher 12 h and 24 h after operation in traditional group than those of improved group (P<0.05), while ALT and AST levels were increased first 12 h after operation and then decreased in both groups (P<0.05). (4) The liver/body weight ratio showed a decreasing trend 12 h after hepatectomy in two groups. The expression of PCNA increased at the beginning of postoperative, and reached its peak at 48 h (P<0.05). However, there was no significant difference at each time point between the two groups. Conclusion By blocking blood flow to establish 70% hepatectomy model in liver fibrosis mice, we can significantly improve the success rate of the model, and reduce the incidence of complications.%目的:探求一种稳定可靠的建立肝纤维化小鼠70%肝切除模型的方法。方法66只C57BL6小鼠按随机数字表法抽取6只作为对照组,剩余60只小鼠先诱导肝纤维化后,与对照组对比观察小鼠肝纤维化模型肝脏的纤维化程度,随机均分为传统组(单纯结扎摘除肝叶,30只)和改良组(阻断血流后摘除肝叶,30只)建立70%肝切除模型。每组分别于肝切除术前和术后12 h、24 h、48 h、72 h 5个时间点处死6只小鼠,收集肝脏组织及血液标本。记录术后2组的成活率和并发症的发生情况;检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,观察肝损伤情况;计算肝质量/体质量比值,并检测增殖细胞核抗原(PCNA)表达来观察2组肝再生状态。结果(1)传统组和改良组小鼠肝纤维化模型均构建成功,可用于70%肝切除。(2)肝部分切除术后,相比传统组,改良组小鼠的成活率显著升高(96.67%vs.73.33%),术中出血、术后腔静脉狭窄及胆漏并发症的发生率明显降低(P<0.05)。(3)术后12 h和24 h,传统组的ALT和AST水平高于改良组,而各组内ALT、AST均于术后12 h时明显升高,之后随时间呈降低趋势(P<0.05)。(4)术后2组肝质量/体质量比值于术后12 h明显降低,之后随时间延长呈缓慢增长趋势,PCNA阳性细胞数均于术后开始升高,在48 h达到高峰后下降(P<0.05),但各时间点2组间差异均无统计学意义。结论通过阻断肝叶血流构建肝纤维化小鼠70%肝切除模型,可显著提高模型的成功率,降低并发症的发生率。
    • 潘凯; 赵强; 陶艳艳; 陈高峰; 刘成海
    • 摘要: 目的 观察健脾补肾方加味对大鼠肝纤维化的治疗效果及对调节性T淋巴细胞(Treg)和辅助性T淋巴细胞(Th) 17的影响.方法 32只雄性Wistar大鼠随机分为正常组、模型组、健脾补肾方组和健脾补肾方加味组,四氯化碳溶液皮下注射造模.用药组在第4周开始分别给予健脾补肾方和健脾补肾方加味,第8周末处死.测定大鼠血清肝功能,观察肝组织炎症及纤维化情况、Foxp3和白细胞介素(IL) 17蛋白与基因表达及血清IL-4和IL-17表达情况.计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验,等级资料比较采用Ridit检验.结果 与正常组相比,模型组大鼠血清总胆汁酸(TBA)、ALP、TBil、ALT和AST均明显升高(P值均<0.05),肝脏胶原沉积明显、α平滑肌肌动蛋白(αSMA)表达增多(P值均<0.05).与模型组相比,健脾补肾组血清ALP、TBA、TBil和ALT均明显降低(P值均<0.05);健脾补肾方加味组血清ALP、TBA、TBil、ALT和AST均明显降低(P值均<0.05);各用药组肝脏胶原沉积和αSMA表达明显减少(P值均<0.05).与健脾补肾方组相比,健脾补肾方加味组TBA、ALT和AST均明显降低(P值均<0.05).与正常组相比,模型组肝组织IL-17蛋白及基因表达显著增高且IL-17和Foxp3基因表达比值显著增高(P值均<0.05),血清IL-17水平明显增高且IL-4和IL-17水平比值明显降低(P值均<0.05).与模型组相比,用药组肝组织IL-17蛋白及基因表达明显降低且IL-17和Foxp3基因表达比值明显降低(P值均<0.05),血清IL-17水平明显降低且IL-4和IL-17水平比值明显增高(P值均<0.05).结论 健脾补肾方加味可以提高抗肝纤维化的治疗效果,其作用机制可能与调节Treg/Thl7失衡有关.
    • 洪晓鹏; 朱耿隆; 李坚; 庄柏润; 陈家帆; 张百萌
    • 摘要: 目的 探讨不同剂量法舒地尔对肝硬化大鼠肝脏缺血再灌注损伤的保护作用.方法 用60%四氯化碳(CCl4)玉米油溶液皮下注射+5%乙醇饮用水的方法制备肝硬化大鼠模型.随机选取成年雄性肝硬化SD大鼠40只,分为假手术组(Sham组)、缺血再灌注组(I/R组)、低剂量法舒地尔1 mg/kg干预组(A组)、高剂量法舒地尔10 mg/kg干预组(B组),各10只.Sham组仅行开关腹手术,A组及B组分别在开腹前30 min腹腔注射法舒地尔1 mg/kg、10 mg/kg,开腹后完全夹闭肝十二指肠韧带(PrinCe法)阻断肝脏血流,30 min后松开血管夹,开放血流再灌注6h后,各组分别取下腔静脉血及肝脏组织,检测大鼠血清中丙氨酸转氨酶(ALT)改变,测定血清中ET-1水平,检测肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,应用实时荧光定量PCR(RT-qPCR)法检测肝脏组织中HIF-1a的mRNA相对定量,取肝组织HE染色后光镜下行病理检查.结果 与L/R组相比,B组血清转氨酶水平、ET-1含量、MDA含量下降,肝组织HIF-1a的mRNA表达下调,SOD活性增高(均P<0.05),肝组织病理损伤减轻.而A组与IR组相比无明显差异(均P>0.05).结论 高剂量法舒地尔可以通过下调HIF-1a表达,降低血清ET-1含量,以及增强机体的抗氧化应激能力,从而对肝硬化大鼠肝脏缺血再灌注损伤提供保护作用.%Objective To investigate the protective effects of different doses of fasudil on hepatic ischemia/reperfussion (I/R) injury in rats with liver cirrhosis.Methods Cirrhosis was induced in rats by subcutaneous injection of 60% carbon tetrachloride (CC14) corn oil solution (0.4 ml/100 g) twice a week for twelve weeks.Five percent of alcohol was given intermittently in drinking water.Then 40 cirrhotic rats were randomized into 4 groups.In sham group,sham operation was performed.In I/R group A and B,whole rat livers were subjected to warm ischemia by clamping the hepatic artery and portal vein for 30 min.In group A,the selected rats were pretreated with low-dose fasudil 1 mg/kg (intraperitoneal injection) 30 min before the induction of ischemia,and in group B,with high-dose 10 mg/kg.The serum levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1),and the liver tissue superoxide dismutase (SOD)activity,malondialdehyde (MDA) content,the expression of HIF-1a (hypoxia-inducible fador-1a) were measured after reperfusion for 6 hours.Hepatic pathologic changes were observed under microscope.Results Compared with I/R group,the serum ALT,AST,ET-1 levels,MDA content and the expression of HIF-1 a were markedly decreased in group B,while the SOD activity significantly increased (P < 0.05).And the pathologic changes were less severe in group B.Conclusion The high-dose fasudil markedly lessened the expression of HIF-1a,up-regulated the concentration of SOD,and lowered the levels of MDA and ET-1,protecting against heoatic ischemia/reperfusion injury in rats with liver cirrhosis.
    • 那坤; 武亮; 李滢; 郑莹; 谢晶日
    • 摘要: 目的:探讨软肝颗粒对肝纤维化大鼠转化生长因子-β1(TGF-β1)/Smads 信号通路的影响。方法105只Wistar大鼠,按随机数字表法随机分为正常对照组,模型组,秋水仙碱组,大黄䗪虫丸组,软肝颗粒高、中、低剂量组,每组15只。采用四氯化碳和高胆固醇饮食诱导肝纤维化。模型制作后,软肝颗粒低、中、高剂量组分别灌胃软肝颗粒混悬液3.600、7.200、14.400 g/(kg•d);大黄䗪虫丸组灌胃大黄䗪虫丸混悬液0.180 g/(kg•d);秋水仙碱组灌胃秋水仙碱混悬液0.108 mg/(kg•d);正常对照组和模型组以等体积蒸馏水灌胃。均连续灌胃8周。采用免疫组化染色法检测肝组织TGF-β1、Smad3、Smad7表达,运用 RT-PCR 技术检测肝组织 TGF-β1、Smad3、Smad7 mRNA 表达。结果与正常对照组比较,模型组TGF-β1[(2.59±0.99)比(0.43±0.21)]、Smad3[(2.56±0.67)比(0.41±0.18)]蛋白及 TGF-β1 mRNA[(2.25±0.21)比(0.71±0.09)]、Smad3 mRNA[(2.34±0.03)比(0.78±0.12)]表达显著升高(P均<0.01)。与模型组比较,软肝颗粒高剂量组TGF-β1[(1.12±0.27)比(2.59±0.99)]、Smad3蛋白[(1.05±0.34)比(2.56±0.67)]表达下降,Smad7蛋白表达[(2.33±0.62)比(0.36±0.18)]升高(P<0.01),TGF-β1 mRNA[(1.09±0.11)比(2.25±0.21)]、Smad3 mRNA[(1.10±0.02)比(2.34±0.03)]表达下降,Smad7 mRNA[(1.18±0.13)比(0.38±0.11)]表达升高(P<0.05)。结论软肝颗粒可通过下调TGF-β1、Smad3,上调Smad7调节肝纤维化大鼠TGF-β1/Smads信号通路。%Objective To investigate the effects of Ruangan granule on transforming growth factor-β1(TGF-β1)/Smads signaling pathway in liver fibrosis in rats. Methods A total of 105 Wistar rats were randomly divided into normal control group, model group and colchicine, Dahuang-Zhechong pill group, high-, medium- and low-dose Ruangan granule groups (n=15 in each group). Liver fibrosis was induced by carbon tetrachloride and a high-cholesterol diet. After modeling, the low-, medium- and high-dose Ruangan granule groups were intragastric administrated Ruangan granule mixed suspension 3.6, 7.2, 14.4 g/(kg•d), respectively;Dahuang-Zhechong pill group was administrated with Dahuang-Zhechong pellets mixed suspension of 0.18 g/(kg•d);the colchicine group was intragastric administrated with colchicine mixed suspension of 0.108 mg/(kg•d);and the normal control group and the model group were intragastric administrated with the equal volume of distilled water. All rats were intragastric administrated for 8 weeks. The expressions of TGF-β1, Smad3 and Smad7 proteins in the liver tissue were detected with immunohistochemical staining method. The expressions of TGF-β1, Smad3, Smad7 mRNAs in the liver tussue were detected by RT-PCR. Results The expressions of TGF-β1 (2.59 ± 0.99 vs. 0.43 ± 0.21) and Smad3 (2.56 ± 0.67 vs. 0.41 ± 0.18) proteins and TGF-β1 mRNA (2.25 ± 0.21 vs. 0.71 ± 0.09) and Smad3 (2.34 ± 0.03 vs. 0.78 ± 0.12) mRNAs in the model group were significantly increased than those in the normal control group (all P<0.01). Compared with the model group, the expressions of TGF-β1 (1.12 ± 0.27 vs. 2.59 ± 0.99) and Smad3 (1.05 ± 0.34 vs. 2.56 ± 0.67) proteins in the high-dose Ruangan granule group decreased significantly, the expression of Smad7 increased significantly (2.33 ± 0.62 vs. 0.36 ± 0.18), and the expressions of TGF-β1 (1.09 ± 0.11 vs. 2.25 ± 0.21) and Smad3 (1.10 ± 0.02 vs. 2.34 ± 0.03) mRNAs decreased significantly, the expression of smad7 mRNA (1.18 ± 0.13 vs. 0.38 ± 0.11) increased significantly (P<0.05). Conclusions Ruangan granule can regulate the TGF-β1/Smads signaling pathway via down-regulation of TGF-β1, Smad3 and up-regulation of Smad7 in liver fibrosis in rats.
    • 贺琴; 李金科
    • 摘要: Objective To investigate the effects of Gynostemma Pentaphyllum on serum markers of liver fibrosis in cholesterol-induced non-alcoholic fatty liver disease (NAFLD) in rabbits. Methods Forty adult male white rabbits were randomly divided into a normal control group, a model group, a treatment group and a simvastatin group, with 10 rabbits in each group. NAFLD was induced with a high-cholesterol diet. After modeling, the rabbits in the treatment group were intragastrically administrated with Gynostemma Pentaphyllum 5 mg/(kg•d), the simvastatin group with simvastatin 5 mg/(kg•d), and the model and normal control groups with the equal volume of distilled water for 9 weeks. The serum levels of total cholesterol (TC) and triglyceride (TG), the serum inflammatory maker C-reactive protein (CRP), the serum markers of liver fibrosis such as hyaluronic acid and laminin (LN), and the TG level in the liver tissue were detected. Results Compared with the normal control group, the serum levels of TC (60.50 ± 9.77 mg/L vs.1.30 ± 0.44 mg/L), TG (1.72 ± 0.61 mmol/L vs. 0.85 ± 0.39 mmol/L), CRP (256.79 ± 30.78 mg/L vs. 8.71 ± 1.41 mg/L), HA (798.8 ± 69.4 ng/ml vs. 121.2 ± 6.8 ng/ml),LN (964.8 ± 62.8 ng/ml vs. 142.4 ± 12.2 ng/ml) in the model group were increased significantly (all P0.05). Conclusions Gynostemma Pentaphyllum may regulate lipid metabolism, alleviate inflammation, and decrease serum markers of liver fibrosis, and might protect against liver fibrosis in rabbits with NAFLD.%目的:探讨绞股蓝对非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)兔肝纤维化血清标记物的影响。方法将40只成年雄性兔按随机数字表法随机分为绞股蓝组、辛伐他汀组、模型组、正常对照组,每组10只。正常对照组给予标准饲料喂养,其余动物给予高脂饲料100 g/d喂养,建立NAFLD模型。绞股蓝组灌胃绞股蓝水煎液5 g/(kg•d),辛伐他汀组灌胃辛伐他汀溶液5 mg/(kg•d),空白组及模型组灌胃等体积蒸馏水。连续给药9周。检测血清总胆固醇(TC)、三酰甘油(TG)、C-反应蛋白(CRP)、透明质酸(HA)、层黏连蛋白(LN)水平及肝组织TG水平。结果与正常对照组比较,模型组血清TG[(1.72±0.61)mmol/L比(0.85±0.39)mmol/L]、TC[(60.50±9.77)mg/L比(1.30±0.44)mg/L]、CRP[(256.79±30.78)mg/L比(8.71±1.41)mg/L]、HA[(798.8±69.4)ng/ml比(121.2±6.8)ng/ml]、LN[(964.8±62.8)ng/ml 比(142.4±12.2)ng/ml]显著升高(P<0.01)。与模型组比较,绞股蓝组血清TG[(1.31±0.39)mmol/L 比(1.72±0.61)mmol/L]、TC[(36.44±6.57)mmol/L比(60.50±9.77)mmol/L]、CRP[(68.77±10.78)mg/L比(256.79±30.78)mg/L]、HA[(420.8±60.2)ng/ml比(798.8±69.4)ng/ml]、LN[(449.8±56.6)ng/ml比(964.8±62.8)ng/ml]以及肝组织TG[(0.52±0.10)mmol/L比(0.77±0.08)mmol/L]显著降低(P<0.01)。绞股蓝组肝组织TG水平[(0.52±0.10)mmol/L比(0.59±0.09)mmol/L]较辛伐他汀组显著降低(P<0.05),但血清TC、TG、CRP、HA和LN水平与辛伐他汀组比较,差异无统计学意义(P>0.05)。结论绞股蓝可调节NAFLD兔血脂代谢,减轻炎症反应,降低肝纤维化血清血清标记物水平,可能对肝纤维化有保护作用。
    • 杨跃武; 刘旭辉; 孔庆磊; 叶志强
    • 摘要: 目的:探讨siRNA沉默c-jun基因对肝硬化大鼠肝切除术后肝再生的影响及其机制。方法建立肝硬化大鼠模型,采用随机数字表法将50只肝硬化大鼠随机分为治疗组和对照组,每组25只。治疗组行肝大部分切除术的同时门静脉内注射慢病毒包装的Pcmv6-AC-GFP/c-jun-siRNA质粒。对照组行肝大部分切除术的同时门静脉内注射PBS。两组大鼠于术后14 d检测门静脉压力、血清ALT及肝重量体重比,采用Western blot法检测肝脏c-jun和增殖细胞核抗原(PCNA)蛋白相对表达量。两组间的数据比较采用t检验。结果治疗组术后平均门静脉压力为(1.18±0.11) kPa,明显小于对照组的(1.67±0.24) kPa(t=-26.74,P<0.05)。治疗组术后ALT为(43±5)U/L,明显低于对照组的(257±14)U/L(t=-31.11,P<0.05)。治疗组术后肝重量体重比为(6.94±0.31)%,明显大于对照组的(2.76±0.14)%(t=23.57,P<0.05)。治疗组术后c-jun和PCNA蛋白相对表达量分别为0.143±0.014、0.195±0.027,对照组相应为0.742±0.057、0.029±0.003,差异有统计学意义(t=-37.17,14.86;P<0.05)。结论慢病毒负载的c-jun-siRNA可能通过下调肝细胞c-jun,上调PCNA蛋白表达来促进肝再生,改善肝硬化大鼠肝切除术后肝功能。%ObjectiveTo investigate the influence and mechanism of c-jun gene silenced by siRNA on liver regeneration in liver cirrhotic rats after hepatectomy.MethodsLiver cirrhotic rat models were established and 50 liver cirrhotic rats were randomized into the treatment group and the control group by random number table method with 25 rats in each group. The rats in the treatment group underwent major hepatectomy and were administered with lentivirus carrying plasmid Pcmv6-AC-GFP/ c-jun-siRNA by intraportal injection, while the rats in the control group underwent major hepatectomy and were administered with phosphate buffer saline (PBS) by intraportal injection. The portal pressure, serum ALT and liver weight/body weight of both groups were tested 14 d after surgery. The relative expression of c-jun in the liver and proliferating cell nuclear antigen (PCNA) protein was detected by Western blot. The data between the treatment group and the control group were compared usingt test.ResultsThe average portal pressure of the treatment group after surgery was (1.18±0.11) kPa, which was signiifcantly lower than (1.67±0.24) kPa of the control group (t=-26.74,P<0.05). ALT of the treatment group after surgery was (43±5) U/L, which was signiifcantly lower than (257±14) U/L of the control group (t=-31.11, P<0.05). Liver weight/body weight of the treatment group after surgery was (6.94±0.31)%, which was signiifcantly greater than (2.76±0.14)% of the control group (t=23.57,P<0.05). The relative expression of c-jun and PCNA protein of the treatment group after surgery was respectively 0.143±0.014 and 0.195±0.027, and those of the control group was respectively 0.742±0.057 and 0.029±0.003, where signiifcant difference was observed (t=-37.17, 14.86;P<0.05).ConclusionLentivirus carrying c-jun-siRNA may promote liver regeneration and improve live function in cirrhotic rats after hepatectomy by down-regulating the c-jun in hepatocyte and up-regulating the PCNA protein.
    • 韦坤; 王兴华; 张海清; 土继政; 石颖; 李娟; 刘小丽
    • 摘要: 目的:探讨肝纤维化指数(liver fibrosis index,LF index)评估肝纤维化程度的可行性.方法:54只新西兰兔皮下注射硫代乙酰胺(thioacetamide,TAA)诱导肝纤维化作为模型组,另取8只新西兰兔为正常对照组.每隔2周随机取2~4只实验兔行实时组织超声弹性成像(real-time tissue elastography,RTE)检查,得出LF index.处死实验兔,取肝组织进行肝纤维化病理分组(S0~S4组),并与病理分期进行对照研究.结果:S2、S3、S4组LF index显著高于正常对照组与S1组(P均<0.05);S3、S4组LF index显著高于S0组、S2组(P均<0.05);LF index随肝纤维化病理分期加重呈增加趋势,二者呈正相关(r=0.718,P<0.05).结论:LF index有望成为无创评估肝纤维化程度的定量指标.
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