丹栀逍遥散对非酒精性脂肪性肝病大鼠LKB1/AMPK/ACC通路及肝脂肪变性的影响  

Effect of Danzhi Xiaoyao Powder on LKB1/AMPK/ACC pathway and hepatic steatosis in rats with nonalcoholic fatty liver disease

作　　者：董璐 曹雅静 薛焕利 何瑾瑜 薛敬东 DONG Lu;CAO Yao-jing;XU Huan-li(Liver disease division,Shaanxi provincial Hospital of Chinese Medicine,(Xian,710003),China)

机构地区：[1]陕西省中医医院肝病科,陕西西安710003

出　　处：《中西医结合肝病杂志》2022年第1期44-48,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：陕西省中医管理局资助项目(No.LCPT010)。

摘　　要：目的:探讨丹栀逍遥散对非酒精性脂肪性肝病(NAFLD)大鼠肝脏激酶B1(LKB1)/腺苷酸活化蛋白激酶(AMPK)/乙酰辅酶A羧化酶(ACC)通路及肝脂肪变性的影响。方法:SD雄性大鼠随机分为空白组、模型组、水飞蓟宾组(26.25 mg·kg^(-1))、丹栀逍遥散高、中、低剂量组(38.0、19.0、9.5 g·kg^(-1)),每组13只。采用高脂饲料连续喂养8周复制非酒精性脂肪肝(NAFLD)大鼠模型。模型复制成功后水飞蓟宾组和丹栀逍遥散各剂量组大鼠开始灌胃给予相应的药物,连续给药4周,给药结束后进行取材和相关指标的检测。给药期间,观察各组大鼠的精神状况、毛色、饮食、活动等一般状态,记录给药前后大鼠体重变化;取大鼠肝、肾、脾脏并称重,计算脏器指数;生化法检测肝组织中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、甘油三脂(TG)、总胆固醇(TC)、游离脂肪酸(NEFA)含量;苏木精-伊红染色(HE)观察各组大鼠肝组织病理变化;Western blot检测肝组织中LKB1、AMPKα1、AMPKα2、ACC及其磷酸化水平。结果:与空白组相比,模型组大鼠毛色发黄暗淡,精神萎靡;体重增量、肝脏指数、肝组织中ALT、AST、TG、TC、NEFA水平均显著升高(P<0.05),肝细胞排列紊乱,胞界不清晰,较多的脂肪空泡;肝细胞中LKB1、p-LKB1、AMPKα1、p-AMPKα1、AMPKα2、p-AMPKα2、p-ACC蛋白表达水平明显降低,ACC蛋白表达升高(P<0.05);与模型组相比,水飞蓟宾组和丹栀逍遥散高、中剂量组大鼠一般状态有不同程度的改善,体重增量、肝脏指数、肝组织中ALT、AST、TG、TC、NEFA水平均显著降低(P<0.05),病理损伤程度减轻;肝细胞中LKB1、p-LKB1、AMPKα1、p-AMPKα1、AMPKα2、p-AMPKα2、p-ACC蛋白表达水平明显升高,ACC蛋白表达降低(P<0.05)。结论:丹栀逍遥散可能通过LKB1/AMPK/ACC信号通路,降低脂肪的合成,改善肝功能,减轻NAFLD模型大鼠肝脂肪变性。Objective:To investigate the effects of Danzhi Xiaoyao Powder on liver kinase B1(LKB1)/AMP-activavted protein kinase(AMPK)/acetyl CoA carboxylase(ACC)pathway and hepatic steatosis in rats with nonalcoholic fatty liver disease(NAFLD).Methods:Male SD rats were randomly divided into blank group,model group,silybin group(26.25 mg·kg^(-1)),high,medium and low dose Danzhi Xiaoyao Powder groups(38.0,19.0,9.5 g·kg^(-1)),with 13 rats in each group.The nonalcoholic fatty liver disease(NAFLD)rat model was established by feeding high-fat diet for 8 weeks.After the model was successfully reproduced,the silybin group and Danzhi Xiaoyao Powder groups were given corresponding drugs by gavage for four weeks.After the administration,the samples were taken and the related indexes were detected.During the administration,the mental status,coat color,diet,activity,and other general states of rats in each group were observed,and the weight changes of rats before and after administration were recorded;the liver,kidney,and spleen were taken and weighed to calculate the organ index;the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and free fatty acid(NEFA)in liver tissue were detected by biochemical method;hematoxylin eosin(HE)staining was used to observe the pathological changes of liver tissue;Western blot was used to detect the expression of LKB1,AMPKα1,AMPKα2,ACC and their phosphorylated proteins.Results:Compared with those in the blank group,the hair color of the model group was yellow and dim,and the spirit was depressed;body weight gain,liver index,levels of ALT,AST,TG,TC,NEFA in liver tissue were significantly higher(P<0.05),the arrangement of hepatocytes was disordered,the cell boundary was not clear,and there were more fat vacuoles.The protein expression levels of p-LKB1,p-AMPKα1,p-AMPKα2 and p-ACC in liver were significantly lower,while the protein expression of ACC was higher(P<0.05).When compared with those in the model group,the general state of rats in

关 键 词：非酒精性脂肪性肝病 丹栀逍遥散 肝脏激酶B1/腺苷酸活化蛋白激酶/乙酰辅酶A羧化酶 肝脂肪变性 

分 类 号：R575.1[医药卫生—消化系统]