扶正养肝化纤汤对CCl_(4)诱导的肝纤维化小鼠的作用机制研究  

Study on the mechanism of Fuzheng Yanggan Huaxian Decoction on CCl_(4)-induced liver fibrosis in mice

作　　者：陈欣 朱婷 臧雪 赵鑫 栾云鹏 李襄 王华宁 CHEN Xin;ZHU Ting;ZANG Xue;ZHAO Xin;LUAN Yunpeng;LI Xiang;WANG Huaning(The First Clinical College,Yunnan University of Chinese Medicine,Yunnan Province,Kunming650021,China;Department of Spleen and Stomach Diseases,the First Affiliated Hospital of Yunnan University of Chinese Medicine,Yunnan Province,Kunming650500,China)

机构地区：[1]云南中医药大学第一临床医学院,云南昆明650021 [2]云南中医药大学第一附属医院脾胃病科,云南昆明650500

出　　处：《中国医药导报》2024年第33期13-19,共7页China Medical Herald

基　　金：云南省科技厅中医联合专项-基础研究计划项目(202301AZ070001-039);云南省科技厅中医联合专项-基础研究专项项目(202301AT070251);云南省教育厅科学研究基金项目(2023Y0475)。

摘　　要：目的初步探索扶正养肝化纤汤对CCl_(4)诱导肝纤维化小鼠的治疗作用及其机制。方法取6周龄19~22 g的SPF级雄性C57BL/6J小鼠48只,根据随机数字表法将其分为空白组,模型组,扶正养肝化纤汤高、中、低剂量组,水飞蓟素治疗组,每组8只。除空白组外,其余5组予5 ml/kg橄榄油+20%CCl_(4)腹腔注射,3次/周,持续8周。模型构建的同期各组给予相应的药物灌胃治疗,1次/d,连续8周。观察小鼠一般状态变化;比较各组肝脏指数,血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、基质金属蛋白酶-1(MMP-1)、金属蛋白酶组织抑制剂-1(TIMP-1)水平;比较各组肝组织MMP-1、TIMP-1 mRNA水平;苏木精-伊红染色观察肝组织病理学变化;免疫荧光染色观察肝脏星状细胞(HSC)变化。结果空白组状态良好;模型组精神萎靡,活动迟缓,皮毛欠光泽,食欲减退;扶正养肝化纤汤高、中、低剂量组毛发干枯稀疏情况好于模型组,饮食、饮水较模型组稍多,活动尚可。造模第3周开始,模型组体重低于空白组;扶正养肝化纤汤高、中、低剂量组体重高于模型组,且扶正养肝化纤汤高剂量组体重下降趋势不明显。模型组肝脏指数,血清ALT、AST水平高于空白组(P<0.05)。扶正养肝化纤汤高、中、低剂量组肝脏指数,血清ALT、AST水平低于模型组(P<0.05);扶正养肝化纤汤高、中剂量组肝脏指数,血清ALT、AST水平低于扶正养肝化纤汤低剂量组;扶正养肝化纤汤高剂量组肝脏指数,血清ALT、AST水平低于扶正养肝化纤汤中剂量组(P<0.05)。模型组血清MMP-1水平、肝组织MMP-1 mRNA水平低于空白组,血清TIMP-1水平、肝组织TIMP-1 mRNA水平高于空白组(P<0.05)。扶正养肝化纤汤高、中、低剂量组血清MMP-1水平、肝组织MMP-1 mRNA水平高于模型组,血清TIMP-1水平、肝组织TIMP-1 mRNA水平低于模型组(P<0.05)。扶正养肝化纤汤高、中剂量组血清MMP-1水平、肝组织MMP-1 mRNA水平高于�Objective To explore the therapeutic effect and me-chanism of Fuzheng Yanggan Huaxian Decoction on CCl_(4)-induced liver fibrosis in mice.Methods A total of 48 SPF grade male C57BL/6J mice aged 6 weeks and weighing 19-22 g were divided into blank group,model group,high-,medium-,and low-dose groups of Fuzheng Yanggan Huaxian Decoction,and Silymarin treatment group according to random number table method,with eight mice in each group.In addition to blank group,the remaining five groups were given 5 ml/kg olive oil+20%CCl_(4)intrabitoneal injection,three times a week,for eight weeks.In the same period of the model construction,each group was given corresponding drug intragastric therapy,once a day,for eight weeks.The general state of mice was observed;liver index,the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),matrix metalloproteinase-1(MMP-1),and tissue inhibitor of metalloproteinase-1(TIMP-1)were compared among all groups;the levels of MMP-1 and TIMP-1 mRNA in liver tissues of all groups were compared;hematoxylin-eosin staining was used to observe the histopathological changes of liver;and the changes of hepatic stellate cells(HSC)were observed by immunofluorescence staining.Results The blank group was in good condition;in model group,the spirit was weak,the activity was slow,the fur was not shiny,and the appetite was decreased;the dry and sparse hair in high-,medium-,and low-dose groups of Fuzheng Yanggan Huayxian Decoction was better than that of model group,and the diet and drinking water were slightly more than that of model group.The liver index and the levels of serum AST and ALT of model group were higher than those of blank group(P<0.05).The liver index and the levels of serum AST and ALT in high-,medium-,and low-dose groups of Fuzheng Yanggan Huayxian Decoction were lower than those of model group(P<0.05).The liver index and the levels of serum AST and ALT in high-and medium-dose groups of Fuzheng Yanggan Huayxian Decoction were lower than those in low-dose group of Fuzhe

关 键 词：肝纤维化 扶正养肝化纤汤 细胞外基质 基质金属蛋白酶 金属蛋白酶组织抑制剂 

分 类 号：R575.5[医药卫生—消化系统]