单硝酸异山梨酯与胰岛素抵抗大鼠大脑细胞凋亡的关系

发布时间：2018-08-05 20:34

【摘要】：目的观察单硝酸异山梨酯(ISMN)对合并有胰岛素抵抗(IR)的大鼠大脑细胞凋亡的影响及探讨其作用机制。方法 14周龄Wistar雄性大鼠40只,分别喂饲普通饲料(普)、高脂高糖饲料(HFHG)及生理盐水(NS)和ISMN灌胃。并据饲料不同随机分成普+NS组(对照组),HFHG+NS组(HFHG组),普+ISMN组(ISMN组),HFHG+ISMN组(UNITED组),每组各10只。喂养12周,取颈动脉血检测血糖浓度及血清胰岛素水平并计算胰岛素抵抗指数(HOMA-IR);取脑组织4份,用TUNEL检测方法观察不同组大鼠脑细胞的病理学改变;用PCR及Western blot检测不同组大鼠大脑细胞中Bcl-2、Bax mRNA及蛋白表达和组织中的一氧化氮(NO)和诱导型一氧化氮合酶(i NOS)含量。结果 (1)脑组织NO含量、i NOS含量、Bax基因mRNA及相关蛋白表达水平,在HFHG组、ISMN组及UNITED组均高于对照组,Bcl-2基因mRNA及相关蛋白表达反之(P0.05);(2)HFHG组大鼠脑组织NO含量与HOMA-IR呈正相关(r=0.739,P0.05),ISMN组大鼠HOMA-IR与脑组织NO含量呈显著正相关(r=0.922,P0.01)。结论 ISMN促进所有组大鼠脑细胞凋亡,而IR会加重脑细胞的凋亡;NO与IR相互诱导,共同作用于大鼠脑细胞凋亡过程;NO起保护或毒性作用与其产生的途径及产生量有关。
[Abstract]:Objective to investigate the effect of isosorbide mononitrate (ISMN) on apoptosis of brain cells in rats with insulin resistance (IR). Methods Forty Wistar male rats aged 14 weeks were fed with normal diet, high fat and high sugar diet (HFHG) and normal saline (NS) and ISMN respectively. According to the feed, they were randomly divided into two groups: normal NS group (control group), ISMN group (HFHG group) and ISMN group (ISMN group) (UNITED group), with 10 rats in each group. After feeding for 12 weeks, the blood glucose concentration, serum insulin level and insulin resistance index (HOMA-IR) were measured by carotid blood test, and the pathological changes of brain cells in different groups were observed by TUNEL assay. PCR and Western blot were used to detect the expression of Bcl-2P Bax mRNA and protein, and the contents of nitric oxide (NO) and inducible nitric oxide synthase (i NOS) in different groups of rats. Results (1) the content of no and I NOS in brain tissue and the expression level of Bax gene mRNA and related protein. The expression of Bcl 2 gene mRNA and related protein in HFHG group and UNITED group was higher than that in control group. On the contrary (P0.05); (2), no content in brain tissue of HFHG group was positively correlated with HOMA-IR (r 0.739 P 0.05). There was a significant positive correlation between HOMA-IR and no content in brain tissue in ISMN group (r 0. 922 P 0. 01). Conclusion ISMN can promote the apoptosis of brain cells in all groups, and IR can increase the apoptosis of brain cells induced by no and IR. The protective or toxic effects of no on the apoptosis of rat brain cells are related to the way of production and the amount of production.
【作者单位】：郑州大学第二附属医院内分泌科;郑州市第一人民医院内分泌科;
【基金】：河南省医学科技攻关计划项目(编号:201303078)
【分类号】：R741

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