孕期酒精暴露诱导仔鼠胰岛素抵抗与海马应激损伤

发布时间：2019-01-05 00:59

【摘要】：目的探讨在孕期酒精暴露模型中胰岛素抵抗与海马应激损伤的相关性及其机制。方法利用C57BL/6J小鼠建立孕期酒精暴露模型,分为对照组、中剂量组和高剂量组;对各组出生第7天(P7)、P14、P30仔鼠进行空腹血糖和空腹血胰岛素测定并计算胰岛素抵抗指数;利用免疫荧光染色法观察各组年龄点仔鼠海马CA1区细胞应激损伤指标c-Fos、核因子-κB(NF-κB)及炎症因子环氧合酶-2(COX2)的阳性细胞数;免疫印迹法检测P7、P14仔鼠海马组织c-Fos、NF-κB激活蛋白的相对表达量以印证免疫荧光染色结果。结果酒精暴露后仔鼠胰岛素抵抗指数升高,且具有酒精剂量依赖性(P0.05,n=90);酒精暴露后各年龄点仔鼠海马组织CA1区应激损伤指标c-Fos、NF-κB和炎症因子COX2阳性细胞数增多,存在酒精剂量依赖性(P0.05,n=90)和长时程效应;孕期酒精暴露后海马组织c-Fos、NF-κB激活蛋白表达量增多(P0.05,n=30),同时存在酒精剂量依赖性和长时程效应,与免疫荧光结果一致。结论孕期酒精暴露可诱导仔鼠产生胰岛素抵抗,其原因可能是氧化应激的结果;胰岛素抵抗可能参与胎儿酒精综合症大脑损伤及其发病机制,c-Fos、NF-κB通路可能是胰岛素抵抗损伤大脑的分子机制之一。
[Abstract]:Objective to investigate the relationship between insulin resistance and hippocampal stress injury in alcohol exposure model during pregnancy. Methods C57BL/6J mice were used to establish the model of alcohol exposure during pregnancy and were divided into three groups: control group, middle dose group and high dose group. Fasting blood glucose and fasting insulin were measured on the 7th day of birth (P7), and insulin resistance index was calculated. The number of positive cells of c-Fos-kappa B (NF- 魏 B) and cyclooxygenase-2 (COX2) in hippocampal CA1 were observed by immunofluorescence staining. The relative expression of c-Fosson-NF- 魏 B activator protein (NF- 魏 B) in hippocampal tissue of P7 and P14 rats was detected by Western blotting to confirm the results of immunofluorescence staining. Results the insulin resistance index of rats exposed to alcohol was increased in a dose-dependent manner (P0. 05). The number of c-Fosson-kappa B and inflammatory factor COX2 positive cells in hippocampal CA1 area of rats at different age points after alcohol exposure was increased, and there was a dose-dependent (P0.05) and long-term effect of alcohol. After alcohol exposure during pregnancy, the expression of c-Fosson-NF- 魏 B activator protein in hippocampus increased (P0.05N ~ (30), and there was a dose-dependent and long-term effect of alcohol, which was consistent with the results of immunofluorescence. Conclusion Alcohol exposure during pregnancy can induce insulin resistance in neonatal rats, which may be the result of oxidative stress. Insulin resistance may be involved in the brain damage and its pathogenesis of fetal alcohol syndrome, and the c-Fossilon NF- 魏 B pathway may be one of the molecular mechanisms of insulin resistance damage to the brain.
【作者单位】：河南大学神经生物学研究所;河南大学淮河临床学院神经内科;
【基金】：国家自然科学基金资助项目(30771140,31070952,30670688,U1204311)
【分类号】：R587

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