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目的观察神经调节素1β(NRG1β)对慢性氧乐果中毒大鼠细胞外调节蛋白激酶(ERK)1/2磷酸化(p-ERK1/2)水平的影响,探索其改善慢性氧乐果中毒认知障碍的作用机制。方法应用Y型电迷宫筛选出有学习记忆能力的大鼠,给予氧乐果5mg/(kg·d)皮下注射4周建立慢性氧乐果中毒认知障碍模型,模型制作成功后治疗组大鼠经侧脑室注射给予NRG1β干预治疗。Y型电迷宫检测大鼠的学习、记忆能力;HE染色观察海马组织的形态学变化;透射电子显微镜观察海马组织超微结构;免疫组织化学和免疫蛋白印迹法检测p-ERK1/2在海马组织内的分布和表达水平。结果 Y型电迷宫结果显示,染毒大鼠学习记忆能力较对照组明显降低,经NRG1β干预治疗后较模型组明显提高;模型组大鼠海马组织损伤明显,ERK1/2磷酸化水平明显下降;NRG1β治疗后海马组织损伤较模型组轻微,ERK1/2磷酸化水平升高。结论 NRG1β可以上调慢性氧乐果中毒大鼠海马组织内ERK1/2的磷酸化(p-ERK1/2)水平,对慢性氧乐果中毒认知障碍有一定的改善作用。
Objective To investigate the effect of NRG1β on the expression of extracellular regulated kinase (ERK) 1/2 phosphorylation (p-ERK1 / 2) in chronic omethoate poisoning rats and to explore its effect on improving chronic omethoate poisoning Know the mechanism of the obstacles. Methods Rats with learning and memory ability were screened by Y-type electric maze, and the model of cognitive impairment was established by subcutaneous injection of omethoate 5 mg / (kg · d) for 4 weeks. After successful model making, the rats in the treatment group After intracerebroventricular injection given NRG1β intervention. The morphological changes of hippocampus were observed by HE staining, the ultrastructure of hippocampus was observed by transmission electron microscopy, the expression of p-ERK1 / 2 was detected by immunohistochemistry and Western blotting in hippocampus Within the distribution and expression level. Results The results of Y-type electric maze showed that the learning and memory abilities of rats exposed to NRG1β were significantly lower than those of the control group, and the levels of phosphorylation of ERK1 / 2 in the model group were significantly lower than those in the untreated group. Compared with the model group, the injury of hippocampal tissue in NRG1β group was mild, and the phosphorylation of ERK1 / 2 increased. Conclusion NRG1β can up-regulate the phosphorylation of ERK1 / 2 in the hippocampus of chronic omethoate poisoning rats, and can improve the cognition of chronic omethoate poisoning.