桃红芪术软肝煎对肝纤维化大鼠病理及TGF-β/Smad信号通路的影响  

Effects of Taohong Qizhu Ruangan Decoction on Pathology and TGF-β/Smad Signal Pathway in Rats with Liver Fibrosis

作　　者：王靖思 吴洁[2] 孙桂芝 张秋云[1,5] 刘玉琴 陈兰羽[2] 朱宏伟[4] Wang Jingsi;Wu Jie;Sun Guizhi;Zhang Qiuyun;Liu Yuqin;Chen Lanyu;Zhu Hongwei(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;Guang＇anmen Hospital of China Academy of Chinese Medical Scienees,Beijing 100053,China;Institute for Medical Researeh,Chinese Academy of Medical Scienees,Beijing Union Medical University,Beijing 100005,China;Department of Pathology,Wangjing Hospital Affiliated to China Academy of Chinese Medical Sciences,Beijing 100102,China;College of Basic Clinical Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京中医医院,北京100010 [2]中国中医科学院广安门医院,北京100053 [3]中国医学科学院中国协和医科大学基础医学研究所,北京100005 [4]中国中医科学院望京医院病理科,北京100102 [5]首都医科大学中医药学院,中医临床基础学学系,北京100069

出　　处：《世界中医药》2018年第6期1499-1505,共7页World Chinese Medicine

基　　金：中国中医科学院博士研究生创新基金(CX201404)

摘　　要：目的:观察桃红芪术软肝煎抗大鼠肝纤维化的作用及对TGF-β/Smad信号通路的影响。方法:选取105只Wistar大鼠,随机分为空白组、模型组、对照药物组(秋水仙碱组、扶正化瘀胶囊组)、桃红芪术软肝煎组(桃红芪术低剂量组、中剂量组、高剂量组)。除空白组外,分3、6、9周3个时间点采用50%CCl41 mL/kg橄榄油溶液腹腔注射进行肝纤维化模型制作,同时进行HE染色和Masson染色观察肝纤维化的病理表现;并采用免疫组织化学法检测肝脏组织的E-Cadherin、Vimentin、转化生长因子(TGF)-β_1、Smad2蛋白表达;RT-PCR方法检测肝脏组织的E-Cadherin、Vimentin、TGF-β_1、Smad2的mRNA表达。结果:肝纤维化病理结果显示,随着造模、给药时间的延长,各给药组均能明显阻断模型大鼠肝组织纤维化进展;与模型组比较,第9周时桃红芪术高剂量组作用最明显。免疫组织化学结果显示,与模型组比较,用药各组从第3周至第9周,E-cadherin表达均较模型组表达明显增加(P<0.05),用药各组间比较,差异无统计学意义(P>0.05);与模型组比较,用药各组TGF-β_1表达明显减弱,差异有统计学意义(P<0.05),用药各组组间比较,差异无统计学意义(P>0.05)。RT-PCR结果显示,与空白组比较,模型组Smad2 mRNA表达量明显升高,差异有统计学意义(P<0.05),桃红芪术低剂量组Vimentin mRNA、Smad2 mRNA表达量明显下降,差异有统计学意义(P<0.05),桃红芪术软肝煎中剂量组Smad2 mRNA表达下降,差异有统计学意义(P<0.05);扶正化瘀胶囊组TGF-β_1 mRNA、Vimentin mRNA表达量均较模型组下降,差异有统计学意义(P<0.05)。结论:桃红芪术软肝煎可持续通过TGF-β/Smad信号通路调节上皮间质转化,治疗肝纤维化。Objective： To observe effects of Taohong Qizhu Ruangan Decoction on treating liver fibrosis of rats,and effects on TGF-β/Smad signal pathway.Methods： A total of 105 Wistar rats were randomly divided into blank group,model group,control group（ colchicine and Fuzheng Huayu Capsule group）,Taohong Qizhu Ruangan Decoction group（ low dose group,middle dose group,high dose group）.Except blank group,the liver fibrosis model was established by the intraperitoneal injection of 50% CCl41 mL/kg of olive oil solution at 3,6,9 week.At the same time,HE staining and Masson staining were used to observe the pathological expressions of liver fibrosis.The expressions of E-Cadherin,Vimentin,TGF-β_1 and Smad2 in liver tissues were detected by immunohistochemistry.The mRNA expressions of E-Cadherin,Vimentin,TGF-β_1 and Smad2 in liver tissues were detected by RTPCR.Results： The pathological results of liver fibrosis showed that with the prolongation of modeling and administration time,each drug-administered group could significantly block the progression of hepatic fibrosis in model rats.And compared with model group,effect of high dose Taohong Qizhu Ruangan Decoction group was most obvious.Immunohistochemical： From 3 week to 9 week,compared with model group,E-cadherin expression was significantly increased than other groups（ P〈0.05）,and there were no differences between groups（ P〈0.05）; compared with model group,TGF-β expression decreased significantly in other drug groups（ P〈0.05）,and there were no differences between groups（ P〈0.05）.RT-PCR： Compared with the blank group,Smad2 mRNA expression in model group significantly increased（ P〈0.05）.Vimentin mRNA and Smad2 mRNA expression of low dose group of Taohong Qizhu Ruangan Decoction significantly decreased（ P〈0.05）.Smad2 mRNA expression of middle dose group of Taohong Qizhu Ruangan Decoction decreased（ P〈0.05）; TGF-β mRNA,Vimentin mRNA expression of Fuzheng Huayu Capsule group decreased compared with the model group（ P�

关 键 词：孙桂芝 桃红芪术软肝煎 肝纤维化 肝硬化 肝纤维化防治 转化生长因子-β/Smad信号通路 上皮-间充质细胞转化 转化生长因子-Β1 

分 类 号：R289.5[医药卫生—方剂学] R575.21[医药卫生—中药学]