姜黄素激活自噬干预非酒精性脂肪肝病模型大鼠氧化应激及炎症反应  

Curcumin ameliorates inflammatory reaction and oxidative stress through activation of autophagy in experimental non-alcoholic fatty liver disease rats

作　　者：吴鹏波[1,2] 宋琪 俞媛洁 饶倩[1,2] 张国 郭一天 谭诗云[1,2] Wu Pengbo;Song Qi;Yu Yuanjie;Rao Qian;Zhang Guo;Guo Yitian;Tan Shiyun(Department of Digestion,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei Province,China;Hubei Provincial Key Laboratory of Digestive Diseases,Wuhan 430060,Hubei Province,China;Department of Digestion,the People’s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]武汉大学人民医院消化内科,湖北省武汉市430060 [2]消化系疾病湖北省重点实验室,湖北省武汉市430060 [3]广西壮族自治区人民医院消化内科,广西壮族自治区南宁市530000

出　　处：《中国组织工程研究》2020年第11期1720-1725,共6页Chinese Journal of Tissue Engineering Research

基　　金：中央部属高校青年教师资助项目(2042017kf0099)，项目负责人：吴鹏波;湖北省自然科学基金(2018CFB236)，项目负责人：吴鹏波;湖北省卫生和计划生育委员会面上项目(WJ2017M019)，项目负责人：谭诗云~~

摘　　要：背景:自噬、氧化应激及炎症反应在非酒精性脂肪肝病中扮演重要角色,姜黄素具有调节自噬、氧化应激及炎症反应等生物活性。目的:探讨姜黄素对非酒精性脂肪肝病大鼠模型保护作用以及机制研究。方法:高糖高脂饮食8周建立非酒精性脂肪肝病大鼠模型,将40只SD大鼠分成对照组、模型组、姜黄素治疗组、姜黄素+3-甲基腺嘌呤组。在第8周末开始干预,对照组和模型组给予PBS灌胃,姜黄素组给予姜黄素500 mg/(kg·d)灌胃,姜黄素+3-甲基腺嘌呤组给予姜黄素500 mg/(kg·d)灌胃及2 mg/(kg·d)自噬抑制剂3-甲基腺嘌呤腹腔注射,干预8周。检测大鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶及总三酰甘油、总胆固醇、空腹血糖浓度;油红O染色观察各组大鼠肝内细胞脂滴分布,透射电镜观察肝细胞线粒体超微结构;采用硫代巴比妥酸法及黄嘌呤氧化酶法测定丙二醛及超氧化物歧化酶活性;Western blot检测自噬及炎症相关蛋白P62、LC3Ⅱ、Beclin-1、NF-κB的表达。实验方案经武汉大学人民医院动物实验伦理委员会批准(批准号2018-541)。结果与结论:①大鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶及总三酰甘油、总胆固醇水平:模型组均高于对照组(P<0.05),姜黄素治疗组显著低于模型组(P<0.05),姜黄素+3-甲基腺嘌呤组高于姜黄素治疗组但低于模型组(均<0.05);②细胞脂质沉积:模型组明显多于对照组;姜黄素治疗组明显少于模型组,姜黄素+3-甲基腺嘌呤组明显高于姜黄素治疗组但低于模型组;③透射电镜观察发现对照组未见明显线粒体损伤,模型组线粒体明显水肿,嵴断裂或消失等,姜黄素可显著缓解线粒体损伤,姜黄素+3-甲基腺嘌呤组对线粒体损失在模型组及姜黄素之间;④肝组织内超氧化物歧化酶水平:模型组显著低于对照组,姜黄素治疗组显著高于模型组,姜黄素+3-甲基腺嘌呤组显著低�BACKGROUND:Autophagy,oxidative stress and inflammatory reactions play an important role in non-alcoholic fatty liver disease.Curcumin has biological activities such as regulating autophagy,oxidative stress and inflammatory reaction.OBJECTIVE:To explore the effect and underlying mechanism of curcumin on experimental non-alcoholic fatty liver disease rats.METHODS:Non-alcoholic fatty liver model was established in rats fed 8-week high-fat diets.Forty healthy SPF male Sprague-Dawley rats were randomly divided into control group,model group,curcumin treatment group,and curcumin and 3-methyladenine(3-MA,an autophagic flux blocker)treatment group.At the end of 8 weeks of high-fat diet,control and model groups were given PBS intragastrically,curcumin treatment group given curcumin 500 mg/kg per day intragastrically,and curcumin+3-MA given curcumin 500 mg/kg per day intragastrically and 3-MA 2 mg/kg per day intraperitoneally.The interventions in each group were given for 8 continuous weeks.The biochemical parameters including serum alanine aminotransferase,aspartate aminotransferase,total triglyceride,total cholesterol,fasting blood glucose level were measured in rats.Oil red O staining was used to characterize the change of hepatic pathology.The ultrastructure of mitochondria was examined by transmission electron microscopy.The hepatic malondialdehyde level and superoxide dismutase activity were measured by thiobarbituric acid method and xanthine oxidase method,respectively.Western blot assay was performed to detect the expression level of autophagic molecular signals including P62,Beclin,LC3B and nuclear factor-κB.The experimental protocol was approved by the Animal Ethic Committee of Renmin Hospital of Wuhan University(approval No.2018-541).RESULTS AND CONCLUSION:The serum alanine aminotransferase,aspartate aminotransferase,total triglyceride,and total cholesterol levels were significantly higher in the model group than the control group(P<0.05).Compared with the model group,curcumin significantly decreased the levels

关 键 词：姜黄素 非酒精性脂肪肝病 自噬 炎症反应 氧化应激 

分 类 号：R446[医药卫生—诊断学] R496[医药卫生—临床医学]