The Neuroprotective Effect Of Polydatin On The Expression Of P53 And Notch1 Against Cerebral Focal Ischemia In Rats

Objective: Cerebral ischemia is the most common type of cerebrovascular disease. With its high morbidity, mortality and disability, cerebral ischemia becomes one of the three most serious illnesses that greatly affect human health in modern society. The pathogenesis of brain tissue injury caused by cerebral ischemia is very complicated. Apoptosis and inflammation are two important aspects of stroke. Upregulation of apoptosis genes and activation of inflammatory factors after cerebral ischemia, have become important targets for clinical treatment.Apoptosis induced by p53 protein plays an important role in the process of nerve cell death following cerebral ischemia, while Notch1 signaling pathway takes part in the inflammatory reaction that causes the brain damage after stroke, therefore, drugs which can depress the activation of p53 and Notch1 signaling pathways are important therapeutic agents for cerebral ischemia.Abundant pharmacology and clinical researches have found that polydatin has anti-inflammatory, anti-apoptosis and anti-tumor effects, but the mechanism underlying is poorly understood.This study observed the influence of polydatin on the expression of p53 and Notch1, and on brain water content in rat MCAO model, to investigate the neuroprotective effect and mechanism of polydatin on cerebral ischemia.Methods: Healthy adult male Sprague-Dawley rats were randomly divided into four groups: Sham operated group, MCAO group, Polydatin low dose group (MCAO + Polydatin 12.5 mg/kg) and Polydatin high dose group (MCAO + Polydatin 50 mg/kg). MCAO model was established by modified Longa method. Polydatin (12.5, 50 mg/kg) was administrated by intraperitoneal injection immediately after cerebral ischemia. Equal volume of physiological saline was administered for MCAO and Sham group in the same manner. 24 h after ischemia, neurological behavior was evaluated, and then rats were sacrificed. Brain water content was measured by wet-dry method. Immunohistochemistry was used to analyze the expression of p53 and Notch1.Results:1 Rats in MCAO group, polydatin high dose group and polydatin low dose group performed a left palsy. Compared with MCAO group, neurological deficit score in polydatin high dose group was decreased(P < 0.05), yet there was no significant difference in the neurological deficit score between polydatin low dose group and MCAO group(P > 0.05).2 In polydatin high dose group, the percentage of brain water content in ipsilateral hemispheres after stroke was decreased comparing with MCAO group(P < 0.05), yet there was no significant difference between polydatin low dose group and MCAO group(P >0.05).3 Comparing with MCAO group, the number of positive cells of p53 and Notch1 was significantly decreased in polydatin high dose group (P < 0.05), but this significant difference did not appear between polydatin low dose group and MCAO group.Conclusions: Treatment with high dose polydatin after stroke could decrease the brain edema. This effect may be related to the down-regulation of p53 and Notch1.