1,25(OH)_2VD_3对Zucker糖尿病肥胖大鼠肝线粒体损伤的保护作用  

Protective effect of 1,25(OH)_2VD_3 on liver mitochondrial injury in ZDF rats

作　　者：李艳艳 冯里茹[1] 张红敏 谭洪兴[1] 朱李佳 王俊[1] LI Yanyan;FENG Liru;ZHANG Hongmin;TAN Hongxing;ZHU Lijia;WANG Jun(Shenzhen Center for Chronic Disease Control,Shenzhen 518020,China)

机构地区：[1]深圳市慢性病防治中心,广东深圳518020

出　　处：《中国比较医学杂志》2018年第11期1-7,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81703226);广东省医学基金(A2016130);深圳市科技计划项目(JCYJ20160428145633098;JCYJ20170307144652484);深圳市卫生计生系统科研项目(201605016);深圳市医疗卫生三名工程项目(SZSM201611017)

摘　　要：目的探讨1,25(OH)_2VD_3对Zucker糖尿病肥胖(Zucker diabetic fatty,ZDF)大鼠肝线粒体损伤的保护作用及相关机制。方法雄性5～6周龄Zucker瘦型(Zucker lean,ZL)大鼠(对照鼠)及ZDF大鼠(模型鼠)按照体重随机分为3组,即对照组(ZL)、模型组(ZDF)及维生素D(vitamin D,VD)干预组(ZDF+VD)。各组大鼠喂养至12周龄后,检测肝损伤、线粒体损伤相关指标及潜在信号通路蛋白的变化。结果与ZL组相比,ZDF组大鼠肝出现严重的脂质沉积,氧化损伤[活性氧簇(ROS)生成增加、丙二醛(MDA)水平明显升高,而谷胱甘肽(GSH)水平明显降低],线粒体肿胀、变性、膜电位显著下降,线粒体生物合成关键蛋白过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)、核呼吸因子-1(nuclear respiratory factor 1,NRF1)和线粒体转录因子A(mitochondrial transcription factor A,TFAM)及上游调控蛋白沉默信息调节因子2相关酶1(sirtuin 1,SIRT1)表达均明显下降,1,25(OH)_2VD_3干预减轻了ZDF大鼠肝氧化损伤、线粒体损伤,上调了SIRT1、PGC-1α、NRF1和TFAM的水平,增强了线粒体生物合成。结论 1,25(OH)_2VD_3可能通过SITR1/PGC-1α介导的线粒体保护机制减轻ZDF大鼠肝损伤。Objective To investigate the protective effect of 1,25(OH)2 VD3 on hepatic mitochondrial injury in ZDF rats and the potential mechanism.Methods Male Zucker rats(5-6 weeks old)were randomly divided into three groups according to their weight:control(ZL),model(ZDF),and 1,25(OH)2 VD3 supplementation(ZDF+VD)groups.All rats were treated to 12 weeks of age,and then the related parameters were analyzed.Results ZDF rats treated with 1,25(OH)2 VD3 showed a significant decrease in serum ALT/AST and liver lipid droplet deposition.Treatment with 1,25(OH)2 VD3 ameliorated mitochondrial injury and increased the expression of mitochondrial biogenesis-related factors SIRT1,PGC-1α,NRF1,and TFAM.Conclusions These findings suggest that 1,25(OH)2 VD3 alleviates diabetic liver injury by improving mitochondrial biogenesis through upregulating SIRT1,PGC-1α,NRF1,and TFAM expression.

关 键 词：1 25(OH)2 VD3 ZDF大鼠 肝氧化损伤 线粒体生物合成 

分 类 号：R-33[医药卫生]