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索拉非尼抑制大鼠肝纤维化的实验研究
作者:孙建鹰  
单位:成都第六人民医院
关键词:索拉非尼 肝纤维化 胶原 
分类号:
出版年·卷·期(页码):2014··第一期(0-)
摘要:

目的:研究索拉非尼对实验性大鼠纤维化过程的影响。方法:Wistar大鼠腹腔注射DMN诱导建立肝纤维化模型。造模后分别以高剂量(10mg/kg)、低剂量(3mg/kg)灌胃。观察各组大鼠肝脏大体变化;HE染色观察病理变化;Masson’s trichrome及Sirius Red染色观察肝细胞内胶原纤维水平,免疫组织化学法测定α-SMA表达。对肝纤维化程度分级,图象分析仪半定量分析。灌胃稀释剂作为对照。结果:肉眼观察治疗,结束后对照组及低剂量组肝脏表面出现单发或多发大小不等的肝纤维化结节,高剂量组大鼠肝脏肝纤维化程度较前两组明显减轻;光镜观察对照组可见肝细胞变性、坏死,纤维组织增生,肝内广泛假小叶纤维化,低剂量组病变程度同对照组类似,高剂量组肝细胞无明显变性,未见广泛再生结节和再分隔。对照组及低剂量组胶原染色面积胶原染色面积无明显差别,高剂量组胶原染色面积分别为模型组和低剂量组的52%、49%,较对照组均有显著差异(P<0.05);对照组及低剂量组α-SMA表达水平不同程度增加,高剂量组α-SMA表达明显减少。结论:索拉非尼能在病理水平减轻实验性模型大鼠的肝纤维化进程。

Objective: To investigate the amelioration of sorafenib on liver fibrosis in rat models. Methods: Liver fibrosis was induced in Wistar rats by intraperitoneal injection of DMN. Rats were gavaged with sorafenib in high dose (10mg/kg) and low dose (3mg/kg). Histological changes were observed by H&E staining, Masson’s trichrome staining and Sirius Red staining. Expression of α-SMA were detected by Immunohistochemistry. Results: The surface of the liver tissue in control group and low dose group appeared solitary or multiple, fibrosis nodules with different sizes. liver fibrosis is significantly ameliorated in high dose group compared to the control group and low dose group. Cell degeneration, necrosis, fibrosis, intrahepatic extensive pseudolobules fibrosis were visible in control group and low dose group by light microscope. No significant degeneration of the liver cells and regenerative nodules in high-dose group were detected. Collagen staining area of collagen staining area between control group and low dose group had no significant difference. Collagen staining area of the high-dose group was 52% or 49% of the control group or low dose group respectively, with significant differences compared to the staining area in control group. α-SMA expression in the control group and low dose group increased significantly compare to expression in high dose group.

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