Effects Of Exercise Preconditioning On Expression Of NRG-1/ErbB4 Pathway Associated Protein In Cerebral Ischemia/Reperfusion Rats

Objective:To investigate the effects of exercise preconditioning on apoptosis and NRG-1 and Erb B4 protein expression after cerebral ischemia/reperfusion injury in rats,and to illustrate the protective mechanism of exercise preconditioning.Methods:Forty-eight male SD rats were randomly divided into four groups,namely,sham control group,exercise preconditioning+sham control group,model control group and exercise preconditioning+model control group,with12 rats in each group(n=12).Middle cerebral artery occlusion(MCAO)ischemia/ reperfusion injury model was established by modified line occlusion method.The exercise preconditioning+sham control group and the exercise preconditioning+model control group were trained on the treadmil for three weeks in advance,meanwhile the sham control group and the model control group were given the same conditions of grasping and feeding,but no other intervention was given.24 h after ischemia/reperfusion,modified Neurological Severity Scores(m NSS)was used to comprehensively evaluate the degree of neurological impairment of rats in each group;HE staining was used to observe the pathological changes of ischemic lateral brain tissues in each group;TUNEL staining was used to detect the expression of apoptosis in ischemic penumbra of rats in each group.Protein expression of NRG-1 and Erb B4 in ischemic penumbra cortex were detected by Western Blot.Results:1.MNSS score of the rats in each group: The rats in the sham control group and the exercise preconditioning+sham control group did not show neurological defects,and differences in scores between the two groups were not statistically significant(P>0.05).Compared with the sham control group,the m NSS scores of rats in the model control group were all increased,and the difference was statistically significant(P<0.01).Compared with the modelcontrol group,the m NSS score of the exercise preconditioning+model control group decreased,and the difference was statistically significant(P<0.01).2.Histopathological changes: The rats in the sham control group and the exercise preconditioning+sham control group showed darker staining of brain tissue,normal cell morphology and structure,and no inflammatory cell infiltration,and the nucleus is larger,the nuclear membrane is clear,and the nucleoli are obvious;In the model control group,the tissue and cell structure of rats on the ischemic side of the brain were loose,with a large number of vacuole-like changes,interstitial edema,obvious inflammatory cell infiltration,and partial apoptotic corpuscles in the visual field.Compared with the model control group,the pathological damage of the ischemic side brain tissue of the rats in the exercise preconditioning+model control group was reduced,the inflammatory cell infiltration was alleviated,and the cell arrangement was more orderly,and the vacuole-like changes were reduced,and the nucleus pyknosis were reduced,and the necrotic neurons were correspondingly reduced.3.Apoptosis of ischemic penumbra cells: Only a few TUNEL positive cells were found in the sham control group and the exercise preconditioning+sham control group,and differences in positive cells between the two groups were not statistically significant(P>0.05).Compared with the sham control group,the TUNEL positive cells in the model control group were all increased,and the difference was statistically significant(P<0.01).Compared with the model control group,the TUNEL positive cells in the exercis preconditioning+model control group was significantly decreased,and the difference was statistically significant(P<0.01).4.Expression of NRG-1 and Erb B4 proteins in ischemic brain tissue:Compared with the sham controlgroup,there was no significant change in NRG-1 and Erb B4 protein expression in the exercise preconditioning+sham control group,and the difference was not statistically significant(P>0.05).Compared with the sham control group,NRG-1 and Erb B4 protein levels inthe model control group were up-regulated,and the difference was statistically significant(P<0.01).Compared with the model control group,NRG-1 and Erb B4 protein levels in the exercise preconditioning+model control group were up-regulated,and the difference was statistically significant(P<0.01).Conclusions:1.Exercise preconditioning could reduce Neurological Severity Scores after cerebral ischemia/reperfusion injury in rats,and reduce the pathological damage of brain tissue of ischemic side,and play the role of cerebral neuroprotection.2.Exercise preconditioning may up-regulate the expression of NRG-1and Erb B4 proteins in cerebral ischemia/reperfusion rats,and inhibit the apoptosis of ischemic penumbra cells,and reduce cerebral ischemia/reperfusion injury.