柯里拉京调控AMPK-自噬信号改善高脂高果糖饮食诱导的小鼠非酒精性脂肪肝病  

corilagin protects non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet via regulating AMPK-autophagy signaling

作　　者：汪晶莹 杜宏梅 陈明 曹辉 童宁 叶明灯 俞斐 WANG Jing-ying;DU Hong-mei;CHEN Ming;CAO Hui;TONG Ning;YE Ming-deng;YU Fei(Dept of Pharmacy,the Second Hospital of Nanjing,Nanjing 210037,China;Dept of Pharmacology,School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China)

机构地区：[1]南京中医药大学附属南京医院(南京市第二医院)药学部,江苏南京210037 [2]安徽医科大学基础医学院药理学教研室,安徽合肥230032

出　　处：《中国药理学通报》2023年第9期1725-1730,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81801064)。

摘　　要：目的探究柯里拉京通过调控AMPK-自噬信号对高脂高果糖饮食诱导的小鼠非酒精性脂肪肝病的影响。方法健康雄性8周龄C57BL/6J小鼠随机分为对照组、模型组和柯里拉京给药组,其中模型组和柯里拉京给药组小鼠于8周龄开始给予高脂高果糖饮食饲养4周,柯里拉京给药组小鼠同时腹腔注射柯里拉京20 mg·kg-1,隔天给药1次,连续给药4周,对照组和模型组给予等剂量生理盐水。造模和给药结束后小鼠处死并记录其肝质量,HE染色、油红O染色、Masson染色观察肝组织病理学特征,试剂盒检测血清和肝脏组织中生化指标,Western blot检测肝脏自噬和p-AMPK水平。结果实验结果发现,模型组小鼠肝质量增加,血清中AST、ALT明显升高,肝脏中出现了大量的脂肪空泡和严重的脂质沉积并有轻度的胶原纤维增生,肝脏中TG水平明显升高,柯里拉京干预后小鼠肝质量降低,肝脏病理改变得到明显改善,TG水平降低;Western blot结果发现,模型组肝脏中Atg7和Atg5等自噬相关蛋白水平明显降低,p-AMPK水平也明显降低,柯里拉京干预后明显升高p-AMPK,并上调自噬水平。结论柯里拉京可以改善高脂高果糖饮食诱导的小鼠非酒精性脂肪肝病,其机制可能是通过促进AMPK磷酸化进而上调自噬水平。Aim To explore the effects of corilagin on non-alcoholic fatty liver disease induced by high-fat and high-sugar diet in mice via regulating AMPK-autophagy signaling.Methods Healthy 8-week-old male C57BL/6J mice were randomly divided into control group,model group and corilagin group.The mice of model group and corilagin group were fed with a high-fat and high-sugar diet for four weeks at the age of eight weeks.The corilagin group mice were also intraperitoneally injected with corilagin(20 mg·kg-1),which was given once every 2 days for 4 weeks.The mice of the control group and the model group were given equal dose of normal saline.After modeling and administration,the mice were sacrificed and the liver weight recorded.The liver pathological changes of each group mice were assessed by HE staining,oil red O staining and Masson staining.The biochemical indexes in serum and liver tissue were detected by the ELISA kit.The p-AMPK and autophagy levels were detected by Western blot.Results The results showed that compared to control group,the liver weight of the model group increased,the AST and ALT levels in serum also significantly increased,there were a large number of fat vacuoles and severe lipid deposition and mild collagen fibrosis in liver,while the liver weight and TG level in liver significantly decreased,and the liver pathological changes were significantly improved after treated with corilagin.Western blot results showed the levels of autophagy related proteins such as Atg7 and Atg5 significantly decreased in the model group,and the p-AMPK level also significantly decreased.When treated with corilagin,p-AMPK and the autophagy levels were up-regulated.Conclusion corilagin can protect non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet.The mechanism may involve increasing p-AMPK level and enhancing autophagy level in liver.

关 键 词：高脂高果糖饮食 非酒精性脂肪肝 柯里拉京 p-AMPK 自噬 

分 类 号：R-332[医药卫生] R343.2R344R345.57R392R575.5