护肝清脂片对非酒精性脂肪肝大鼠肝脏中AMPK通路激活及NF-κB-p65蛋白的影响  

Effect of Hugan Qingzhi tablets on AMPK pathway activation and NF-κB-p65 protein expression in the liver of rats with nonalcoholic fatty liver disease

作　　者：姚笑睿 夏凡[1] 唐外姣[1] 周本杰[1] 

机构地区：[1]南方医科大学珠江医院药学部,广东广州510282

出　　处：《南方医科大学学报》2017年第1期56-62,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(81274160);广东省自然科学基金(S2012010009380)~~

摘　　要：目的探讨护肝清脂片对高脂饮食诱导的非酒精性脂肪肝(NAFLD)大鼠脂质代谢和炎症反应的影响及可能的作用机制。方法将大鼠随机分为6组:模型组、正常组、非诺贝特组(0.1 g/kg)、护肝清脂片低(0.54 g/kg)、中(1.08 g/kg)、高(2.16 g/kg)剂量组。在高脂饲料造模的同时给予相应的药物持续给药12周。HE染色观察各组肝脏形态学及病理学变化,采用全自动生化分析仪检测血清甘油三酯(TG)、胆固醇(CHOL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平及肝组织TG、CHOL水平,酶联免疫吸附法(ELISA)测定肝组织TNF-α、IL-6、CRP水平。q RT-PCR技术检测肝组织SREBP-1c、FASN的m RNA水平,Western blotting检测肝组织p-AMPK、SREBP-1c、FASN及NF-κB-p65的蛋白水平。结果护肝清脂片中、高剂量组能减轻NAFLD大鼠肝脏脂质沉积,显著降低其血清TG、CHOL、AST、ALT水平,同时降低肝组织TNF-α、IL-6、CRP水平。护肝清脂片中、高剂量组显能著升高NAFLD大鼠肝脏p-AMPK的蛋白表达水平,降低SREBP-1c、FASN及NF-κB-p65的表达水平。结论护肝清脂片可能通过激活AMPK通路改善肝脏脂质代谢及抑制NF-κB活性减轻肝细胞炎症反应,缓解NAFLD进程。Objective To investigate the effect of Hugan Qingzhi tablets on lipid metabolism and inflammation in rats fed on high-fat diet and explore the underlying mechanisms. Methods Sixty male Sprague-Dawley rats were randomly divided into 6 groups, namely HFD group （with high-fat diet and distilled water）, control group （with normal diet and distilled water）, fenofibrate group （with high-fat diet and treatment with 0.1 g/kg fenofibrate suspension）, and low-, moderate-and high-dose Hugan Qingzhi tablet groups （with high-fat diet and treatment with 0.54, 1.08, and 2.16 g/kg Hugan Qingzhi suspension）. After daily corresponding treatments for 12 weeks, the histological changes in the liver were observed with HE staining. The serum levels of triglyceride （TG）, cholesterol （CHOL）, alanine transaminase （ALT）, and aspartate aminotransferase （AST）, and the levels of TG and CHOL in the hepatic tissue were assayed. The proinflammatory cytokines TNF-α, IL-6 and CRP were detected with enzyme-linked immunoassay, and p-AMPK, SREBP-1c, FASN and NF-κB-p65 expression levels in the liver were determined with qRT-PCR or Western blotting. Results At high and moderate doses, Hugan Qingzhi effectively decreased the levels of ALT, AST, TG and CHOL levels in the serum, lowered the hepatic levels of TNF-α, IL-6 and CRP, enhanced p-AMPK, and reduced the expression of SREBP-1c, FASN and Ac-NF-κB-p65 in the liver of rats fed on high-fat diet. Conclusion Hugan Qingzhi tablets alleviates hyperlipidemia and inflammation in rats fed with high-fat diet possibly by activating AMPK pathway and suppress NF-κB activity to arrest the progression of nonalcoholic fatty liver disease.

关 键 词：非酒精性脂肪肝 护肝清脂片 脂质代谢 炎症 

分 类 号：R285.5[医药卫生—中药学]