活性维生素D3对2型糖尿病大鼠肝脏的保护作用及机制研究

发布时间：2018-06-25 19:07

本文选题：活性维生素D3 + 2型糖尿病　；参考：《新疆医科大学》2016年硕士论文

【摘要】：目的:探讨活性维生素D3对2型糖尿病大鼠肝组织中C-Jun氨基末端激酶/C-Jun(JNK/C-Jun)炎症通路表达的影响及其发挥肝脏保护作用的可能机制。方法:采用高脂高糖饮食联合小剂量STZ(30 mg/kg)腹腔注射的方式制备2型糖尿病大鼠模型。将SD大鼠随机分为正常对照组(NC)、糖尿病非干预组(DM)、活性维生素D3干预组(VD)。VD组以0.03μg/(kg·d)的骨化三醇(溶于花生油)灌胃,NC组和DM组以花生油灌胃。8周后处死,分离血清测定空腹血糖(FBG)、空腹胰岛素(FINS)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三酯(TG),计算稳态模型胰岛素抵抗指数(HOMA-IR);留取肝组织,HE染色观察肝脏组织病理学变化;实时荧光定量PCR测定JNK,C-Jun及其下游肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β的mRNA表达;免疫组化和Western blotting测定上述炎症因子蛋白表达。结果:1.与NC组相比,DM组FBG、HOMA-IR、ALT、AST、TC及TG水平增加,FINS水平降低(P0.05);与DM组相比,VD组仅有ALT、AST及TG、HOMA-IR下降有统计学意义(P0.05)。2.与NC组相比,DM组大鼠肝细胞肿胀、脂肪变性伴有炎细胞浸润;VD组上述病理变化较DM组显著减轻。3.DM组JNK,C-Jun,TNF-α和IL-1β的mRNA和蛋白表达均高于NC组(P0.05),VD干预后上述炎症因子的表达低于DM组(P0.05)。结论:1.小剂量STZ腹腔注射联合高脂高糖饮食喂养16周的SD大鼠呈现血糖、血脂、肝功能、胰岛素水平及其敏感性的异常;肝细胞肿胀、脂肪变性伴有炎细胞浸润;JNK/C-Jun及其下游炎症因子表达的上调。2.活性维生素D3对糖尿病大鼠的糖脂代谢紊乱具有一定的积极作用。3.活性维生素D3可能通过下调JNK/C-Jun炎症通路发挥改善糖尿病肝脏病变的作用。4.本试验中0.03μg/(kg·d)的活性维生素D3可对糖尿病大鼠的肝脏产生一定的积极影响。不良反应最小,治疗作用最佳的活性维生素D3剂量尚需进一步研究。
[Abstract]:Aim: to investigate the effect of active vitamin D _ 3 on the expression of C-Jun N-terminal kinase / C-Jun (JNK-C-Jun) inflammatory pathway in liver tissues of type 2 diabetic rats and the possible mechanism of its protective effect on the liver. Methods: type 2 diabetic rats were induced by high fat and high sugar diet combined with low dose STZ (30 mg/kg) intraperitoneal injection. SD rats were randomly divided into normal control group (NC), diabetic non-intervention group (DM), active vitamin D _ 3 intervention group (VD) .VD group with 0.03 渭 g / (kg d) ossification triol (dissolved in peanut oil) intragastric perfusion of NC group and DM group with peanut oil after 8 weeks of death. Fasting blood glucose (FBG), fasting insulin (fins), alanine aminotransferase (alt), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG) were measured, and the homeostasis model insulin resistance index (HOMA-IR) was calculated. The mRNA expression of JNKN C-Jun and its downstream tumor necrosis factor- 伪 (TNF- 伪) and interleukin-1 尾 (IL-1- 尾) were detected by real-time fluorescence quantitative PCR, and the expression of these inflammatory cytokines was detected by immunohistochemistry and Western blotting. The result is 1: 1. Compared with NC group, the levels of TC and TG in DM group increased and decreased significantly (P0.05), while in VD group compared with DM group, the decrease of alt AST and TG HOMA-IR were statistically significant (P0.05). 2. The level of FBGG-HOMA-IR in DM group was significantly lower than that in DM group (P0.05), and that in VD group was significantly lower than that in DM group (P0.05). Compared with NC group, the pathological changes of hepatocyte swelling, fatty degeneration with inflammatory cell infiltration in VD group were significantly reduced compared with NC group. 3. The mRNA and protein expressions of JNKC-Jun-TNF- 伪 and IL-1 尾 in DM group were significantly higher than those in NC group (P0.05). The expression of above inflammatory factors in VD group was lower than that in DM group (P0.05). Conclusion 1. Low dose STZ combined with high fat and high glucose diet for 16 weeks showed abnormal blood glucose, blood lipid, liver function, insulin level and sensitivity. Fatty degeneration associated with inflammatory cell infiltration JNK-C-Jun and its downstream inflammatory factor expression. 2. 2. Active vitamin D 3 has a positive effect on glucose and lipid metabolism disorder in diabetic rats. Active vitamin D 3 may play a role in ameliorating diabetic liver disease by down-regulating the JNK- C-Jun inflammatory pathway. In this experiment, the activity of vitamin D _ 3 of 0.03 渭 g / (kg d) had a positive effect on the liver of diabetic rats. The best dose of active vitamin D 3 for treatment needs further study.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1

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