补肾降浊饮对非酒精性脂肪肝大鼠胰岛素抵抗的影响  

Intervention Effect of Bushen Jiangzhuoyin on Insulin Resistance on Rat Nonalcoholic Fatty Liver Disease

作　　者：吕宝伟[1] 冯春青[2] 孙建光[1] LYU Bao-wei;FENG Chun-qing;SUN Jian-guang(Shandong University of Traditional Chinese Medicine, Ji＇nan 250355, China;Liaocheng People＇s Hospital, Liaocheng 252000, China)

机构地区：[1]山东中医药大学,济南250355 [2]聊城市人民医院,山东聊城252000

出　　处：《中国实验方剂学杂志》2018年第12期107-113,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：山东省高等学校科技计划项目(J09LF14)

摘　　要：目的：研究补肾降浊饮对非酒精性脂肪肝（NAFLD）大鼠胰岛素抵抗（IR）的干预作用,探讨其对胰岛素信号通路中细胞因子及激酶等的影响。方法：将60只SD大鼠随机分为正常组、模型组、补肾降浊饮低、中、高剂量组（10,15,20 g·kg^-1）及水飞蓟宾葡甲胺组（19 g·kg^-1）,正常组予普通饲料喂养,其余各组予高脂饲料喂养并同时灌胃生理盐水或相应剂量药物干预。12周后检测各组大鼠血清总胆固醇（TC）,甘油三酯（TG）,丙氨酸氨基转移酶（ALT）,天门冬氨酸氨基转氨酶（AST）,空腹血糖（FBG）,胰岛素（INS）水平,胰岛素抵抗指数（IRI）,胰岛素敏感指数（ISI）及肝组织中脂联素（ADP）,游离脂肪酸（FFA）,肿瘤坏死因子-α（TNF-α）,超氧化物歧化酶（SOD）,丙二醛（MDA）含量;苏木素-伊红（HE）染色、油红O染色检测肝组织脂肪变性程度;蛋白免疫印迹法（Western blot）检测大鼠肝组织中c-Jun氨基端激酶1（JNK1）,磷酸化c-Jun氨基端激酶（p-JNK）及胰岛素受体α（IRα）,磷酸化胰岛素受体底物1丝氨酸307位点（p-IRS-1）表达水平。结果：与正常组比较,模型组大鼠TG,TC,ALT,AST,FBG,INS,IRI,TNF-α,FFA,MDA水平及JNK1,p-JNK及p-IRS-1蛋白表达显著升高,ISI,ADP,SOD水平显著降低（P〈0.01）;与模型组比较,补肾降浊饮低、中、高剂量组可不同程度降低大鼠血清中TG,TC,ALT,AST,FBG,INS,IRI,TNF-α,FFA,MDA水平及JNK1,p-JNK及p-IRS-1蛋白表达（P〈0.05,P〈0.01）,升高ISI,ADP,SOD水平（P〈0.05,P〈0.01）;相较于水飞蓟宾葡甲胺组,补肾降浊饮高剂量组疗效显著（P〈0.01）。结论：补肾降浊饮可改善非酒精性脂肪肝大鼠胰岛素抵抗,其机制可能与提高ADP含量,减轻氧化应激,抑制JNK信号通路进而增强胰岛素受体底物活性有关。Objective： To study the intervention effect of Bushen Jiangzhuoyin on insulin resistance of nonalcoholic fatty liver disease,in order to explore it＇s effect on cytokines and kinases in insulin signaling pathway.Method： Totally 60 SD rats were randomly divided into blank group,model group,low-dose,middle-dose and high-dose Bushen Jiangzhuoyin groups（ 10,15,20 g·kg^-1） and silybin meglumine group（ 19 g·kg^-1）. The blank group was fed with normal diet,the other groups were fed with high-fat diet and given normal saline or the corresponding dose of medicines. All of the rats were put to death after 12 weeks,the levels of total cholesterol（ TC）,triglyceride（ TG）,alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,fasting blood glucose（ FBG）,insulin（ INS）,insulin resistance index（ IRI）,insulin sensitivity index（ ISI） in serum and adiponectin（ ADP）,free fatty acid（ FFA）,tumor necrosis factor-α（ TNF-α）,superoxide dismutase（ SOD）,malondialdehyde（ MDA） in liver were detected; HE staining and oil red O staining were used to detect the degree of fatty degeneration of liver tissue; the expression levels of c-Jun amino terminal kinase1（ JNK1）,insulin receptor α（ IRα）,phosphorylated insulin receptor substrate 1 serine 307（ p-IRS-1） were detected by Western blot method. Result： Compared with blank group,model group showed significant increases in levels of TG,TC,ALT,AST,FBG,INS,IRI,TNF-α,FFA and MDA,and JNK1,p-JNK and p-IRS-1 protein expressions,and significant decreases in ISI,ADP,SOD levels（ P〈0. 01）; compared with model group,low-dose,middle-dose and high-dose Bushen Jiangzhuoyin groups showed different degrees of reduction in rat serum TG,TC,ALT,AST,FBG,INS,IRI,TNF-α,FFA,MDA levels,and JNK1,p-JNK,p-IRS-1 protein expressions（ P〈0. 05,P〈0. 01）,and rise in ISI,ADP,SOD levels（ P〈0. 05,P〈0. 01）; compared with silybin meglumine group,highdose Bushen Jiangzhuoyin group showed a significant efficacy（ P〈0. 01�

关 键 词：非酒精性脂肪肝 胰岛素抵抗 脂联素 C-JUN氨基端激酶 胰岛素信号通路 补肾降浊饮 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]