Effects Of Inhibition Of HMGB1 Expression On The Expression Of Apoptosis-related Proteins Bcl-2 And Bax After Cerebral Ischemia/Reperfusion In Rats

Objective:Construction of middle cerebral artery occlusion/reperfusion(MCAO/R)model in rats.HMGB1-specific inhibitor were used to inhibit the expression of HMGB1 expression.The neuroprotective effect of HMGB1 was evaluated by observing the symptoms of neurological deficits and infarct volume.To observe the expression of HMGB1,Bcl-2and Bax in ischemic penumbra,and to explore the correlation between the expression of HMGB1 and the expression of Bcl-2 and Bax in the neuroprotective effect.Methods:120 healthy SD male rats(weighing 250-300g),96 of them were randomly divided into four groups: sham operation group,model group,glycyrrhizin intervention group(GL group)and ethyl pyruvate intervention group(EP Group(each group of 24).Sham operation group only separated from the neck blood vessels,not occlusion of the middle cerebral artery(MCA).The MCAO/R model was prepared by reversible thread emboliz-ation,and reperfusion was given after 1 hour of ischemia.GL group(50mg / kg),EP(50mg / kg)were injected intraperitoneally,sham operation group and model group were intraperitoneally injected with the same amount of normal saline in the GL group and the EG group at the same time.The rats were divided into four subgroups(6 rats in each subgroup).The behavioral characteristics of the rats were observed at different time points(6h,12 h,24h,48h)after reperfusion.Functional defect score.The expression of HMGB1,Bcl-2 and Bax positive cells in ischemic penumbra were measured byimmunohistochemistry.The expression of HMGB1,Bcl-2 and Bax positive cells in ischemic penumbra was detected by HE staining.The remaining 24,according to the above method is also divided into four groups(each group of 6),ischemia 1h reperfusion24 h,the rapid decisive brain,using TTC staining to measure the infarct volume.Results:(1)Neurological deficit score: Compared with the model group,the use of GL or EP intervention to inhibit HMGB1 expression,neurological score was significantly lower,statistically significant(p<0.05).(2)24 h after reperfusion TTC staining: compared with model group,use of GL or EP after intervention inhibit HMGB1 expression,infarct volume was significantly narrowed,statistically significant(p<0.05).(3)HE staining: after using GL or EP intervention to suppress the expression of HMGB1,nerve cells are closely aligned,and necrotic cells are rare,compared to the model group.(4)after 48 hreperfusion immunohistochemical determination of HMGB1 expression:use GL or EP after intervention inhibit HMGB1 expression,compared with model group,ischemia and half dark band HMGB1 expression significantly reduced,statistically significant(p<0.05)(5)immunohistochemical determination of the Bcl-2,Bax expression: 1 h ischemia reperfusion during the 48 h,after using GL or EP intervention inhibit HMGB1 expression,compared with model group,expression the Bcl-2 antiapoptotic proteins increased,with statistical significance(p<0.05).Apoptotic protein Bax was significantly reduced and statistically significant(p<0.05).Conclusion:After cerebral ischemia/reperfusion in rats,inhibition of HMGB1 expression by drug intervention can significantly improve the symptoms of neurological deficits andreduce the infarct volume.Inhibition of HMGB1 expression after neuroprotective effects and upregulation of Bcl-2 and down-regulated Bax.