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神经调节素1β对慢性氧乐果中毒大鼠学习记忆障碍的治疗作用
Therapeutic effect of neuregulin1β on the dysfunction of learning and memory in rats with chronic omethoate poisoning
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 observe the effect of neuregulin1β (NRG1β) on the level of phosphorylated extracellular regulated protein kinase(ERK)1/2 (p-ERK1/2), and explore the therapeutic mechanism of NRG1β on the cognitive dysfunction in rats with chronic omethoate poisoning. Methods Rats with strong learning and memory ability were selected by Y-electric maze test to establish the cognitive impairment model by subcutaneous injection of omethoate［5mg/(kg·d)］ for 4 weeks. After the model was established, rats in the treatment group were injected with NRG1β into their ventricles. The cognitive capacity of rats was evaluated with Y-electric maze. The morphology and ultrastructure of hippocampus were observed by haematoxylin eosin (HE) staining and transmission electron microscopy (TEM) respectively. The expression of p-ERK1/2 was determined by immunohistochemical (IHC) staining and Western blotting. Results Y-electric maze test showed the cognitive ability in rats with omethoate exposed (model and treatment groups) reduced significantly compared with normal rats, but the ability of treated rats was improved obviously compared with that of model rats. In compare with normal rats, obvious injury of hippocampus was observed in the model group by HE staining and TEM, and the phosphorylation level of ERK1/2 decreased significantly. In the rats treated with NRG-1β, the injury was milder than the model rats, and the phosphorylation level of ERK1/2 increased significantly. Conclusion In the chronic omethoate poisoning rat, NRG-1β can promote the phosphorylation level of ERK1/2 in hippocampus, and may play an important role in the improvement of cognitive function.
神经调节素1β / 氧乐果 / 认知障碍 / 细胞外调节蛋白激酶 / 免疫印迹法 / 大鼠
Neuregulin 1β / Omethoate / Cognitive dysfunction / Extracellular regulated protein kinase / Western blotting / Rat
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