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孕期酒精暴露诱导仔鼠胰岛素抵抗与海马应激损伤
Prenatal alcohol exposure inducing insulin resistance and stress injury in mouse hippocampi
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（P <0.05，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（P <0.05, 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（P <0.05,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。
Objective To investigate the relationship of prenatal alcohol exposure inducing insulin resistance and the stress injury in the mouse hippocampi.
Methods C57BL/6J mice were used to establish the models of prenatal alcohol exposure with control group, moderate ethanol group and high ethanol group. The pups of different groups at postnatal day 7(P7), P14 and P30 were gathered for the measurements of fasting blood glucose and blood insulin. The insulin resistance index (HOM-IR) was calculated. The stress injury in hippocampal CA1 area was observed. For instance, the expression of stress injury proteins, c-Fos and NF-κB, of hippocampus at P7 and P14 was tested with immunofluorescent labeling and Western blotting to analysis. Results After prenatal alcohol exposure, fasting glucose and insulin resistance index increased with dose dependency and long term effect (P<0.05,n=90). After prenatal alcohol exposure, c-Fos and NF-κB positive cells increased in hippocampi with dose dependency and long term effect (P<0.05,n=90). The expression of c-Fos and NF-κB proteins with Western blotting in hippocampus was harmonized with the results of immunocytochemistry (P<0.05,n=30). Conclusion The prenatal alcohol exposure can induce pups insulin resistance, and the insulin resistance is probably caused by stress injury. In addition, the insulin resistance may be involved in the pathogenesis and brain injuries of fetal alcohol syndrome, through c-Fos and NF-κB pathway.
孕期酒精暴露 / 胰岛素抵抗 / 氧化应激 / 海马 / 应激损伤 / 免疫荧光法 / 免疫印迹法 / 小鼠
Prenatal ethanol exposure /
Insulin resistance /
Oxidative stress /
Hippocampus /
Stress injury /
Immunofluorescence /
Western blotting /
Mouse
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