二甲双胍对D-氨基半乳糖联合Pam3CSK4诱导的SD大鼠的急性肝损伤及炎症反应的作用及机制  

Metformin attenuates acute liver injury and inflammatory response induced by D-galactosamine in combination with Pam3CSK4 in SD rats

作　　者：武丽涛 孙娟 王愉涵 郭进露 刘艳[3] 杜小娟 闫小飞 张富军 李冬民[1,2] WU Litao;SUN Juan;WANG Yuhan;GUO Jinllu;LIU Yan;DU Xiaojuan;YAN Xiaofei;ZHANG Fujun;LI Dongmin(Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences of Xi'an Jiaotong University Health Science Center Xi'an 710061,China;Key Laboratory of Environment and Genes Related to Diseases,Ministry of Education of China,Xi'an 710061,China;Clinical Medicine (five year program) of Grade 2013,Xi'an 710061,China)

机构地区：[1]西安交通大学医学部基础医学院生物化学与分子生物学系,陕西西安710061 [2]西安交通大学环境与疾病相关基因教育部重点实验室,陕西西安710061 [3]西安交通大学2013级临床医学五年制,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2018年第1期41-46,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81370952);陕西省科技计划项目(No.2013K212203);2015年西安交通大学省级大学生创新训练项目(No.89)

摘　　要：目的研究二甲双胍在D-氨基半乳糖联合Pam3CSK4(以下简称DP)诱导的SD大鼠急性肝损伤动物模型中的抗损伤及抗炎作用。方法选取18只雄性SD大鼠腹腔注射D-氨基半乳糖(350mg/kg)和Pam3CSK4(50μg/kg)混合液构建急性肝损伤大鼠模型,干预组大鼠分别给予PBS与二甲双胍。分别称量大鼠肝重、体质量并评估肝/体质量比变化;通过HE染色观察大鼠肝脏病理改变;收集大鼠空腹血清用于检测血清转氨酶(ALT、AST)水平;同时通过ELISA与RT-qPCR检测肝组织中促炎因子(IL-6与TNF-α)的表达水平;最后通过Western blotting检测大鼠肝脏中MAPK信号通路的活化情况。结果与对照组相比,两干预组的肝重比、血清转氨酶以及促炎因子IL-6与TNF-α的表达水平均显著升高;同时肝细胞水样变性与肝间质渗出表明DP成功构建了SD大鼠急性肝损伤模型。与PBS干预组相比,二甲双胍干预组肝重比降低,肝细胞损伤明显减轻;血清转氨酶与促炎因子的表达水平均显著下降;同时肝组织中p-ERK1/2、p-SAPK/JNK、p-P38MAPK的蛋白表达降低,提示二甲双胍可能通过抑制MAPK信号通路发挥抗炎作用。结论二甲双胍在DP成功诱导的SD大鼠急性肝损伤动物模型中减轻了炎症反应。Objective To investigate the anti injury and anti inflammation protective effects of metformin in acute liver injury SD rat model induced by D-galactosamine and Pam3CSK4.Methods Eighteen male Sprague Dawley rats were treated with the mixture of D-galactosamine(350mg/kg)and Pam3CSK4(50μg/kg)by intraperitoneal injection(i.p.)to construct acute liver injury model.The rats in intervention group were given PBS and metformin,respectively.The liver and body weight were measured and the ratio of liver weight to body weight was calculated.HE staining was used to observe the pathological changes of the liver.Fasting serum was collected for detection of serological parameters.ELISA and RT-qPCR were used to determine the expression levels of IL-6and TFN-α.Finally,activation of MAPK signal pathway in rat liver was detected by Western blot.Results Compared with those in control group,the ratio of body weight to liver weight,serum transaminase and proinflammatory cytokines IL-6and TNF-αwere all significantly increased in the two intervention groups.Meanwhile,hepatic degeneration and hepatic interstitial exudation indicated that D galactosamine combined with Pam3CSK4successfully constructed acute liver injury model in the SD rats.Compared with PBS group,the ratio of body weight to liver weight,hepatic damage,serum transaminase levels,and the expressions of proinflammatory cytokines IL-6and TNF-αwere significantly decreased in metformin treated group.Meanwhile,the expressions of p-ERK1/2,p-SAPK/JNK and p-P38MAPK decreased in liver tissues by metformin pretreatment,suggesting that metformin may play an anti inflammatory effect by suppressing MAPK signaling pathway.Conclusion Metformin attenuated inflammatory reactions in SD rats with acute liver injury induced by D-galactosamine and Pam3CSK4.

关 键 词：D-氨基半乳糖 Pam3CSK4 二甲双胍 急性肝损伤 炎症 

分 类 号：R34[医药卫生—基础医学]