The Therapeutic Mechanism Of Neuregulin-1β On The Cognitive Dysfunction In Rats With Chronic Organophosphate Poisoning

Objective:To observe the effects of neuregulin-1β (NRG-1β) on the phosphorylated activity level of ERK1/2(p-ERK1/2), and explore the therapeutic mechanism of NRG-1β on the cognitive dysfunction in rats with chronic organophosphate poisoning.Method:Rats with strong learning and memory ability,49in total, were selected by Y-electric maze test. Among which,15rats were selected randomly as control group, and the rest were used to build chronic organophosphate poisoning cognitive impairment models by injected omethoate5mg/kg subcutaneously every day for4weeks.29rats were successfully established as cognitive impairment models, and were randomly divided into model group of14rats and treatment group of15rats. On the first day and the eighth day after the models established, rats in treatment group was injected with NRG-1β into their left and right lateral ventricles respectively, while the normal group and model group were given equal volume of PBS simultaneously. Y-electric maze was used to examine the learning and memory ability of rats. The morphology and ultrastructure of hippocampus were observed by haematoxylin eosin(HE) staining and transmission electron microscopy(TEM) respectively; and the expression of p-ERK1/2and ERK1/2was determined by immunohistochemical(IHC) staining and Western blotting(WB).Result:Y-electric maze test showed the learning and memory 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 hippocampal can be observed in model group by HE staining and TEM, and the phosphorylated activity level of ERK1/2decreased significantly; and in rats with NRG-1β treated, the injury was milder than model rats, and the phosphorylated activity level of ERK1/2increased significantly; and the expression of ERK1/2in each group has no significant difference.Conclusion:In chronic organophosphate poisoning rats, NRG-1β can activate the ERK1/2signaling pathway in hippocampus, thus playing an important role in the improvement of cognitive impairment...