GW7647对大鼠非酒精性脂肪性肝病(NAFLD)的治疗作用  

Therapeutic Effect of GW7647 on Non-alcoholic Fatty Liver Disease in Rats

作　　者：徐永芳[1] 吴娜 胡月新[3] 赵永美 郑绍鼎 危玲 郑思佳 刘建军 XU Yong-fang;WU Na;HU Yue-xin;ZHAO Yong-mei;ZHENG Shao-ding;WEI Ling;ZHENG Si-jia;LIU Jian-jun(Dept.of Reproductive Medicine,The 1st People's Hospital of Yunnan Province,Kunming Yunnan 650032;School of Basic Medicine,Kunming Medical University,Kunming Yunnan 650500,China;Incubation Center for Scientific and Technological Achievements,Kunming Medical University,Kunming Yunnan 650500,China;Graduate School,Kunming Medical University,Kunming Yunnan 650500,China;Biomedical Engineering Research Center&Yunnan Key Laboratory of Stem Cell and Regenerative Medicine,Kunming Medical University,Kunming Yunnan 650500,China)

机构地区：[1]云南省第一人民医院生殖医学科,云南昆明650032 [2]昆明医科大学基础医学院,云南昆明650500 [3]昆明医科大学科技成果孵化中心,云南昆明650500 [4]昆明医科大学研究生院,云南昆明650500 [5]昆明医科大学生物医学工程研究中心暨云南省干细胞与再生医学重点实验室,云南昆明650500

出　　处：《昆明医科大学学报》2021年第8期17-22,共6页Journal of Kunming Medical University

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2017FE468(-082),2018FE001(-027),2018FE001(-194),202001AY070001-129];云南省卫生科技计划基金资助项目[2017NS241];云南省教育厅科学研究基金资助项目[2018JS191]。

摘　　要：目的通过建立大鼠非酒精性脂肪性肝病(NAFLD)模型,研究过氧化物酶体激活剂受体(PPARα)激动剂GW7647对大鼠NAFLD的治疗作用。方法采用灌胃给药的方式,给予大鼠GW7647药物干预,每日1次,连续6周。灌胃结束后,采集大鼠血样进行胰岛素抵抗、血脂水平及肝损伤相关生化指标检测,并对大鼠肝组织进行相关的病理学检测(HE和油红O染色)。结果6周的药物治疗后发现,GW7647治疗能显著减轻NAFLD大鼠体重,使糖耐受得到改善、恢复对胰岛素敏感;肝脏染色显示肝病理改善和脂滴积累减少;血清胆固醇、甘油三酯含量降低;血清AST和ALT结果显示改善了肝损伤。结论PPARα激动剂GW7647通过减轻体重、减少肝脏脂肪积累、恢复大鼠胰岛素敏感性以及改善大鼠肝损伤和降低血脂水平等指标起到对NAFLD大鼠的治疗作用。Objective To establish a rat model of nonalcoholic fatty liver disease(NAFLD) and to explore the therapeutic effect of peroxidase activator receptor(PPAR) agonist GW7647 on rat NAFLD. Methods After the experimental animals were grouped,GW7647 was administered daily for 6 consecutive weeks. After intragastric administration,blood samples were collected for the detection of insulin resistance,blood lipid levels and liver injury-related biochemical indexes,and pathological tests(HE and oil red O staining) were performed on the liver tissues of the rats. Results After 6 weeks of treatment,GW7647 significantly reduced body weight,improved glucose tolerance and restored insulin sensitivity in NAFLD rats. Liver staining showed improvement in liver pathology and decreased accumulation of lipid droplets;serum cholesterol and triglyceride levels decreased;and serum AST and ALT levels showed improved liver injury(P < 0.05). Conclusion PPARα agonist GW7647 has a therapeutic effect on NAFLD rats by reducing body weight, reducing liver fat accumulation, restoring insulin sensitivity,improving liver injury and reducing blood lipids.

关 键 词：过氧化物酶增殖物受体 非酒精性脂肪性肝病 高脂饮食 PPARα激动剂GW7647 

分 类 号：R96[医药卫生—药理学]