摘要
目的:观察柴胡疏肝散对TGF-β1/p38MAPK信号通路的影响,探索其抗肝纤维化的作用机制。方法:50只Wister大鼠按随机数字表法分为正常对照组、病理模型组、柴胡疏肝散高、中、低剂量组5组。除正常组外,其余各组均用腹腔注射CCl4制备肝纤维化模型。各治疗组于第6周给药至第10周结束。免疫组化S-P法检测肝组织转化生长因子-β1(TGF-β1)、p38丝裂原活化蛋白激酶(p-p38MAPK)、α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶MMP-9和金属蛋白酶组织抑制因子TIMP-1蛋白的表达。结果:与模型组比较,柴胡疏肝散中剂量组TGF-β1蛋白、p-p38MAPK和α-SMA蛋白表达显著减弱,MMP-9蛋白表达显著增强,TIMP-1蛋白表达显著减弱。结论:柴胡疏肝散有明显的抗肝纤维化作用。其机制可能与柴胡疏肝散经TGF-β/p38MAPK信号传导通路抑制肝星状细胞(HSC)活化,使HSC低表达TIMP-1、高表达MMP-9从而促进基质降解有关。
Objective To observe the effects of Chaihu Shugan Powder on the signaling pathways of TGF-β1 / p38 MAPK and explore its action mechanism for anti-hepatic fibrosis. Methods 50 Wister rats were randomly divided into five groups:normal control group,pathologic model group,three Chaihu Shugan Powder groups of high dose,mediate dose and low dose respectively. Expect for the normal group,the rats in the rest groups were all made into liver fibrosis models by intraperitoneal injection of CCl4. Each treatment group was given Chaihu Shugan Powder from the 6th week to the 10 th week. The expressions of transforming growth factor-β1( TGF-β1),p38motogen-activated protein kinase( p38MAPK),α-smooth muscle actin( α-SMA),matrix metalloproteinase-9( MMP-9),and tissue inhibitive factor of metalloproteinase( TIMP-1) in hepatic tissue were detected by S-P immunohistochemical method. Result Compared with the model group,the protein expression of TGF-β1,p38 MAPK,α-SMA in the Chaihu Shugan Powder group of mediate dose declined markedly,while the expression of the TIMP-1 protein increased significantly and the expression of TIMP-1 protein declined remarkably. Conclusion: Chaihu Shugan Powder has obvious efficacy of anti-hepatic fibrosis. The action mechanism may be related with its inhibition of the hepatic stellate cell( HSC) by the signaling pathway of TGF-β / p38 MAPK,which realizes the low expression of TIMP-1,the high expression of MMP-9 and the enhanced matrix degradation.
出处
《中国中医基础医学杂志》
CAS
CSCD
北大核心
2016年第1期62-65,共4页
JOURNAL OF BASIC CHINESE MEDICINE
基金
河南省教育厅科学技术研究重点资助项目(12B360010)