活性维生素D3干预保护2型糖尿病模型大鼠肝脏的作用机制  

Action mechanisms of active vitamin D3 on protecting the liver of type 2 diabetes mellitus rats

作　　者：刘莉娜[1] 王志强[2] 朱筠[1] 

机构地区：[1]新疆医科大学第一附属医院内分泌科,新疆维吾尔自治区乌鲁木齐市830054 [2]新疆医科大学第一附属医院代谢疾病实验室,新疆维吾尔自治区乌鲁木齐市830054

出　　处：《中国组织工程研究》2016年第5期694-700,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81160116)~~

摘　　要：背景:活性维生素D3在2型糖尿病及其并发症发生发展中发挥着重要的调节作用。目的:探讨活性维生素D3干预保护2型糖尿病模型大鼠肝脏的作用及其机制。方法:将35只雄性SD大鼠随机分为正常对照组、糖尿病模型组和维生素D3干预组,后2组高脂高糖饮食并腹腔注射链脲佐菌素制备糖尿病大鼠模型。维生素D3干预组予以0.03μg/(kg·d)的骨化三醇灌胃(溶于花生油),正常对照组和糖尿病模型组以花生油灌胃。8周后麻醉处死,分离血清测定空腹血糖、空腹胰岛素、总胆固醇、三酰甘油,计算稳态模型胰岛素抵抗指数;留取肝组织,行苏木精-伊红染色、免疫组织化学染色、实时荧光定量PCR。结果与结论:1与糖尿病模型组相比,维生素D3干预组仅有三酰甘油、稳态模型胰岛素抵抗指数下降(P<0.05)。2与正常对照组相比,糖尿病模型组大鼠肝细胞肿胀、脂肪变性伴炎细胞浸润,JNK和C-Jun及其磷酸化形式的蛋白表达、JNK和C-Jun及其下游的肿瘤坏死因子α、白细胞介素1β的m RNA表达均升高(P<0.05);维生素D3干预组肝细胞肿胀及脂肪变性减轻,炎细胞浸润减少,同时上述全部因子的表达亦低于糖尿病模型组(P<0.05)。3结果证实,维生素D3保护2型糖尿病模型大鼠肝脏的作用机制可能与其下调JNK/C-Jun信号通路有关。BACKGROUND： Active vitamin D3 plays an important role in the development of type 2 diabetes and its complications. OBJECTIVE： To explore the influence of active vitamin D3 on the liver of type 2 diabetes mellitus rats, and its mechanisms. METHODS： A total of 35 male Sprague-Dawley rats were randomly divided into normal control group, diabetes group and vitamin D3 group. In the diabetes group and vitamin D3 group, rats received high fat and high sugar diet and intraperitoneal injection of streptozotocin to prepare rat models of diabetes mellitus. In the vitamin D3 group, rats were intragastrically given calcitriol dissolved in peanut oil 0.03 μg/kg per day. In the normal control group and diabetes group, rats were intragastrically given peanut oil. 8 weeks later, rats were sacrificed and serum was isolated. Fasting blood glucose, fasting insulin, total cholesterol and triacylglycerol levels were measured. Insulin resistance index in the steady-state model was calculated. The liver was retained, and subjected to hematoxylin-eosin staining, immunohistochemical staining, and real-time fluorescent quantitative PCR. RESULTS AND CONCLUSION：（1） Compared with the diabetes group, triacylglycerol and insulin resistance index were lower in the vitamin D3 group（P〈0.05）.（2） Compared with the normal control group, swelling of the liver cells and fatty degeneration with inflammatory cell infiltration were found. Protein expression of JNK and C-Jun and phosphorylation levels, m RNA expression of JNK and C-Jun, tumor necrosis factor α and interleukin-1β increased in the diabetes group（P〈0.05）. Liver cell swelling and fatty degeneration lessened, inflammatory cell infiltration reduced in the vitamin D3 group. Simultaneously, the expression of above factors was lower in the vitamin D3 group than in the diabetes group（P〈0.05）.（3） Results suggested that the protective effect of vitamin D3 on the liver of rats with type 2 diabetes was possibly associated with its effect on downregulating JNK/C-J

关 键 词：骨化三醇 糖尿病 2型 炎症 组织工程 实验动物 内分泌系统损伤与修复动物模型 活性维生素D3 2型糖尿病 SD大鼠 肝脏 C-JUN氨基末端激酶 胰岛素抵抗 糖尿病动物模型 链脲佐菌素 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]