疟母丸抑制CCl_4诱导小鼠肝纤维化进程的作用

Effect of Nuemu Pills on the process of liver fibrosis induced by CCl_4 in mice

目的探讨疟母丸(三棱、莪术和鳖甲)对CCl4诱导小鼠肝纤维化的干预作用。方法采用10%CCl4橄榄油溶液腹腔注射,制备小鼠肝纤维化模型。制模40只小鼠分为模型组(14只),疟母丸组(13只)以及索拉菲尼(Sorafenib)治疗组(13只),另有10只未处理作正常组。采用血清肝功能、肝组织病理及α-SMA评价药物干预效果。结果 (1)模型小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性及总胆红素(TBil)均显著升高(P<0.01或P<0.05),白蛋白(Alb)显著降低(P<0.05)。与模型组比较,疟母丸组和索拉菲尼治疗组ALT、AST、TBil均显著降低(P<0.01或P<0.05),且疟母丸组Alb显著增加(P<0.01)。(2)模型小鼠肝组织炎症反应及胶原纤维沉积显著增加,已形成完整包绕的假小叶结构,肝组织羟脯氨酸(Hyp)显著增高(P<0.01)。与模型组比较,疟母丸组和索拉菲尼治疗组肝脏炎症反应、胶原沉积较轻,肝组织Hyp显著降低(P<0.05)。(3)免疫印迹分析显示模型小鼠肝组织α-平滑肌肌动蛋白(α-SMA)表达显著增加(P<0.01)。与模型组比较,疟母丸组和索拉菲尼治疗组α-SMA表达均显著降低(P<0.01)。结论疟母丸能够显著抑制CCl4诱导小鼠肝纤维化的进程。

AIM To explore the effect of Nuemu Pills （Sparganii Rhizoma, Curcumae Rhizoma, Trionycis Carapax） on the process of the CC14-induced liver fibrosis in mice. METHODS Liver fibrosis model in mice was established by intraperitoneal injection of 10% CCl4-olive oil （2 mL/kg）. Forty mice were divided into the control group （14 mice） treated with olive oil, two treatment groups treated with Sorafenib （13 mice）, and Nuemu Pills （ 13 mice）, respectively, and normal group （ 10 mice） as comparison. Mice were sacrificed at the end of the ex- periment, liver histological changes, liver function associated with liver fibrosis in mice were observed. RESULTS （ 1 ） At the end of the sixth week of modeling, serum levels of alanine aminotransferase （ ALT）, aspartate ami- notransferase （AST） increased gradually in mice （P 〈0. 01 or P 〈0.05）, serum levels of albumin （Alb） decreased in mice （P 〈0. 05 ）, and serum levels of total bilirubin （TBil） increased significantly compared with the control group. Compared with the model group, the serum levels of ALT, AST, and TBil decreased remarkably in the Sorafenib and Nuemu Pills treatment groups, and Alb increased remarkably in the Nuemu Pills group. （2） Compared with the control group, the inflammation and collagen deposition in liver of the model group increased significantly. Pathological changes in liver showed a complete package of pseudolobule structure, and the hydroxyproline content Of hepatic tissue rose （P 〈 0. 05 ）. Compared with the model group, the inflammation, col- lagen deposition and hydroxyproline content in liver were alleviated dramatically （P 〈 0. 05 ） in both Sorafenib and Nuemu Pills groups. （3） Compared with the control group, protein expression of α-smooth muscle actin remarkably increased （P 〈0.01 ） in the model group. Protein expression of α-smooth muscle actin in the liver decreased in both Sorafenib and Nuemu Pills groups （P 〈 0. 01 or P 〈 0. 05）. CONCLUSION The CCl4-induced liver fibrosis in mice can be suppressed by Nuemu Pills.