黄芪后处理对大鼠肝纤维化中的影响及TGF-β_1/Smad2、p38MAPK作用

Effects of TGF-β_1/Smad2, p38MAPK Signaling Pathway on Huangqi Postconditioning among Hepatic Fibrosis Rat Models

目的:研究黄芪对CCl4诱导的大鼠肝纤维化肝组织中TGF-β1、Smad2和p38MAPK表达的影响,探讨TGF-β信号通路在黄芪后处理中可能的抗纤维化机制。方法:60只Wistar大鼠被随机分成对照组、模型组、黄芪后处理组及鳖甲软肝片组,其中黄芪后处理组又分为小剂量组、常规剂量组和大剂量组,大鼠背部皮下注射CCl4构建肝纤维化模型,分别用HE和VG染色法染色,肝纤维化程度直接在光学显微镜下观测。同时采用SABC免疫组化方法检测各实验组TGF-β1、Smad2和p38MAPK的表达情况。结果:与对照组比较,模型组TGF-β1、Smad2表达明显增强(P<0.05),而p38MAPK表达显著下降(P<0.05)。与模型组比较,黄芪后处理各组中大鼠肝组织中TGF-β1表达均有减弱(P<0.05),且随着黄芪剂量的增加而减少;随着黄芪剂量增加逐步下调Smad2的表达(P<0.05)、上调p38MAPK的表达(P<0.05)。此外,黄芪组大鼠肝脏病理变化显著改善。结论:黄芪后处理明显影响大鼠肝组织TGF-β1信号表达,且对CCl4诱导的大鼠肝纤维化的作用呈剂量依赖性增强,其可能的机制为负性调节TGF-β1,减少Smad2及增强p38MAPK的表达。

This article was aimed to study the effects of Huangqi postconditioning on TGF-β1, Smad2 and p38MAPK signaling proteins expressed in hepatic fibrosis rat models induced by CCl4 in order to detect the molecular mecha-nism for anti-fibrotic. Sixty Wistar rats were randomly divided into the control group, model group, Huangqi postcon-ditioning group, and Bie-Jia Ruan-Gan Pian （BJRGP） group. And the Huangqi postconditioning group was subdivid-ed into the low dosage group, normal dosage group and high dosage group. The hepatic fibrosis rat models were es-tablished with the administration of CCl4. The changes of liver tissues in histology were measured by HE and VG dyeing methods. And the degree of hepatic fibrosis was directly observed with optical microscope. Immunohistochemi-cal techniques were used to measure transforming growth factor beta 1（TGF-β1）, Smad2 and p38MAPK signaling protein expression. The results showed that compared with the control group, expressions of TGF-β1 and Smad2 were increased obviously, but the expression of p38MAPK was decreased obviously in the model group. Compared with the model group, the TGF-β1 expression in each group postconditioned with Huangqi was decreased （P〈 0.05）. And the decreasing was along with the dosage increasing of Huangqi. When the dosage of Huangqi increased, the expression of Smad2 was downregulated significantly（P〈 0.05） and the expression of p38MAPK was upregulated significantly （P〈 0.05）. Furthermore, pathological changes of liver tissues among rats in Huangqi groups were improved significantly. It was concluded that the Huangqi postconditioning can obviously influence the TGF-β1 signaling pathway in liver nbsp;tissues among rats. And the effect on CCl4-induced hepatic fibrosis rat models was dose-dependent increase. The mechanism may be associated with the negative regulation of TGF-β1, decreasing of Smad2 and increasing of p38MAPK expression.