| Objective:To observe the effects of exercise preconditioning on neural function after cerebral ischemia/reperfusion injury and the related factors in the classical pyroptosis pathway,we explored the possible mechanism of exercise preconditioning on cerebral ischemia/reperfusion injury.Methods:The 160 SPF SD male rats were randomly divided into 4 groups: exercise preconditioning+sham group(EP+Sham),sham group(Sham),exercise preconditioning group(EP)and model group(Model).No intervention was carried out on the model group and sham group,the exercise preconditioning+sham group and exercise preconditioning group rats were subjected to a 4-week exercise intervention using a rotating wheel treadmill.Cerebral ischemia/reperfusion models were established 24 h after the last exercise preconditioning in each group.At 6h,12 h,and 24 h after reperfusion,mNSS was used to evaluate neuromotor function of rats in each group;TTC staining was used to determine relative cerebral infarction volume 24 h after reperfusion;At 6h,12 h,and 24 h after reperfusion,HE staining was used to observe the pathological damage of ischemic brain in each group;Western blot detected the expression of pyroptosis-related proteins NLRP3,Caspase-1,and GSDMD in ischemic brain tissue of rats;The content of inflammatory factors IL-1β and IL-18 in ischemic brain tissue of rats was measured by ELISA.Results:1.mNSS:After 6h,12 h,24h of cerebral ischemia/reperfusion,compared with rats in the exercise preconditioning+sham group and sham group,the mNSS score of rats in the model group were significantly higher at each time point(P<0.01);Compared with the model group,the mNSS score of rats in the exercise preconditioning group decreased significantly at each time point(P<0.01).2.TTC staining:After 24 h of cerebral ischemia/reperfusion,the rats in the exercise preconditioning+sham group and the sham group did not show any cerebral infarction,the relative cerebral infarction volume of rats in the model group was significantly increased(P<0.01);Compared with the model group,the relative cerebral infarction volume of rats in the exercise preconditioning group was significantly reduced(P<0.01).3.HE staining:After 6h,12 h,24h of cerebral ischemia/reperfusion,the rats in the exercise preconditioning+sham group and the sham group showed no obvious tissue pathological damage.The brain tissue of rats in the model group was loose,neurons were arranged in disorder,and the structure was significantly damaged,with some nerve cells disappearing;Compared with the model group,the degree of brain tissue damage and neuronal degeneration in the exercise preconditioning group were alleviated at each time point.And after6 h,12h,24 h of cerebral ischemia/reperfusion,the degree of pathological damage to the ischemic side of the brain tissue in rats gradually worsens with time.4.The expression of NLRP3,Caspase-1,and GSDMD proteins in the ischemic brain tissue of rats in each group:After 6h,12 h,24h of cerebral ischemia/reperfusion,the NLRP3,Caspase-1,and GSDMD proteins in the exercise preconditioning+sham group and the sham group were all at basal expression,and the difference between the two groups was not statistically significant(P>0.05);The expression levels of NLRP3,Caspase-1,and GSDMD proteins in the model group were significantly upregulated(P<0.01);Compared with the model group,the expression levels of NLRP3,Caspase-1,and GSDMD proteins in the exercise preconditioning group were significantly downregulated(P<0.05).5.The content of inflammatory factor IL-1β and IL-18 in ischemic brain tissue of rats in each group:After 6h,12 h,24h of cerebral ischemia/reperfusion,both IL-1β and IL-18 were basal expression in the exercise preconditioning+sham group and sham group,and the difference between the two groups was not statistically significant(P>0.05);The content of IL-1β and IL-18 increased significantly in the model group(P<0.01);Compared to the model group,the content of IL-1β and IL-18 decreased significantly in the exercise preconditioning group(P<0.01).Conclusions:1.Exercise preconditioning can reduce the relative cerebral infarction volume and severity after cerebral ischemia/reperfusion injury in rats.2.Exercise preconditioning can improve the pathological damage of the ischemic area in rats with cerebral ischemia/reperfusion injury,reduce the degree of neurological damage after cerebral ischemia/reperfusion injury,and exert neuroprotective effects.3.Exercise preconditioning can reduce the expression of NLRP3,Caspase-1,and GSDMD proteins related to the classic pyroptosis pathway in the brain tissue of rats after cerebral ischemia/reperfusion injury.And it can reduce the release of inflammatory factor IL-1β and IL-18 downstream of pyroptosis in the ischemic brain tissue of rats,alleviate inflammatory damage after cerebral ischemia/reperfusion. |
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