索拉非尼抑制大鼠肝纤维化的体内实验研究

The study of Sorafenib inhibited hepatic fibrosis in rats in vivo

目的:研究索拉非尼对实验大鼠肝纤维化过程的影响。方法:取Wistar大鼠24只腹腔注射二甲基亚硝胺(dimethylnitrosamine,DMN)诱导建立肝纤维化模型。造模成功后分别以索拉非尼溶液高剂量(1 ml·kg-1)、低剂量(0.3 ml·kg-1)灌胃,将稀释剂灌胃大鼠作为对照组。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。对肝纤维化程度采用图像分析仪半定量分析。结果:模型动物给药处理后,大体观察见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,高剂量组肝纤维化程度较前两组明显减轻。光镜观察显示: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;低剂量组病变程度与对照组类似;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无明显差异,高剂量组胶原染色面积分别为对照组和低剂量组的52%、49%,差异均有统计学意义(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表达则明显减少(P<0.05)。结论:索拉非尼能减轻实验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.