【作者】 朱海燕；

【导师】 谢春光；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2013， 博士

【摘要】 目的：拟探寻参芪复方对糖尿病大血管病变中骨骼肌的保护作用,并揭示其作用机理,为临床用药提供理论依据。方法：KKAy小鼠喂饲含有L-NAME饮水同时喂饲高脂饲料以复制2型糖尿病大血管病变模型。入选小鼠随机分为KKAy组、模型组、参芪复方组和罗格列酮组,每组15只。另设15只C57BL/6J小鼠为正常组,共5组。造模同时开始给药,连续8周,期间观察动物一般状况,摄食饮水情况,体重变化情况,监测血糖。实验结束后测量各组小鼠血脂、血清胰岛素,计算胰岛素抵抗指数,观察腹主动脉、骨骼肌的形态学改变,并应用基因芯片技术对参芪复方组-模型组、模型组-KKAy组的骨骼肌进行差异基因检测。结果：参芪复方可改善模型动物的一般状态,减少多饮、多食的状况,减轻体重,降低血糖,降低血清TC、 TG水平(P<0.05)。参芪复方可减轻模型动物腹主动脉内膜水肿,减轻骨骼肌细胞萎缩、水肿、断裂和炎症状况。参芪复方组-模型组、模型组-KKAy组的差异表达基因均涉及多个生物学过程和多个信号通路,两个比较组差异基因均涉及的生物学过程为细胞死亡,均涉及的信号通路为代谢途径和细胞周期。两个比较组呈逆向表达的7条差异基因为Celsr2、 Rilp11、 Dlx6as、2010004M13Rik、Anapc13、 Gm6097、Ddx39b。结论：参芪复方可改善模型动物的一般状态,减轻其多饮、多食、肥胖的状况,可降低血糖,调节糖、脂代谢紊乱状态。参芪复方可改善模型动物骨骼肌细胞萎缩、水肿、断裂和炎症状况,减轻骨骼肌细胞的损伤。参芪复方可对糖尿病大血管病变中骨骼肌起保护作用,其机理可能与调节细胞死亡途径、调节代谢和细胞周期通路以及调控Celsr2、Rilp11、 Dlx6as、2010004M13Rik、 Anapc13、 Gm6097、 Ddx39b基因表达有关。更多还原

【Abstract】 Objective:To explore the protective effects and mechanisms of ShenQi compound recipe on the skeletal muscle of diabetic macrovascular complication, provide a theoretical basis for the clinical use of drugs.Methods:The KKAy mice fed water containing Nco-nitro-L-arginine Methyl Ester (L-NAME) and high fat diet at the same time to copy the macrovascular complications of type2diabetes model. Selected KKAy mice were randomly divided into KKAy group, model group, ShenQi compound recipe group and rosiglitazone group (n=15), another15C57BL/6J mice as the normal group, a total of five groups. Modeling at the same time began to be fed drugs for8weeks. During the experiment periodes, observed the general status and measured the account of the water drinking, food intake and body weight, monitored blood glucose. After the end of the experiment, measured each group of mice blood lipids, serum insulin, calculated insulin resistance index, observed the morphological changes of the abdominal aorta and skeletal muscle, and used gene chip technology to detect differentially expressed genes of the ShenQi compound recipe and model group, model group and KKAy group.Results:ShenQi compound recipe could improve the general state of the KKAy mice, reduce polydipsia, polyphagia, lose weight, lower blood sugar, reduce serum TC, TG level (P<0.05). ShenQi compound recipe could improve abdominal aortic intimal edema, improve the gastrocnemius muscle atrophy, edema, fracture, inflammatory state situation. Differentially expressed genes between ShenQi compound recipe group and model group were involved in many biological processes and pathways. Differentially expressed genes between model group and KKAy group were also involved in many biological processes and pathways. Two comparison groups differentially expressed genes were all involved in the biological process of cell death, were all involved in signaling pathways of metabolic pathways and cell cycle. In two comparison groups7genes (Celsr2, Rilpll, Dlx6as,2010004M13Rik, Anapc13, Gm6097, Ddx39b) expression in reverse were found.Conclusion:ShenQi compound recipe had the role of improving the general state of the KKAy mice, reducing KKAy mice polydipsiapolyphagia, obesity status, lower the blood suglar and regulating the disorder of glucose and lipid. The ShenQi compound recipe had the role of improving skeletal muscle of DM macrovascular complication atrophy, edema, fracture, inflammatory state. The effects and mechanisms of ShenQi compound recipe on the skeletal muscle of diabetic macrovascular complication may be relationed to regulate cell death process, metabolic and cell cycle pathways and regulate the gene expression of Celsr2, Rilpll Dlx6as,2010004M13Rik, Anapc13, Gm6097and Ddx39b.更多还原