Effects Of Dexmedetomidine On Vascular Endothelial Glycocalyx In Mice With Cerebral Ischemia-Reperfusion Injury

ObjectiveTo investigate whether dexmedetomidine plays a protective role in cerebral ischemia and reperfusion injury through the vascular endothelial glycocalyx pathway.MethodsIn this experiment,110 male C57 mice aged 8 to 12 weeks and weighing 25 to 30g were selected as the research object.All mice were randomly divided into a sham operation group(S group,n=15),sham operation+dexmedetomidine group(SD group,n=15),ischemia-reperfusion group(R group,n=40)and ischemia-reperfusion+dexmedetomidine group(RD group,n=40).Dexmedetomidine(25?g/kg)was intraperitoneally injected into SD group and RD group 30 minutes before operation,and equal dose of normal saline was intraperitoneally injected into group S and R.Subsequently,a transient focal cerebral ischemia-reperfusion injury model was established.24 hours after MCAO,TTC staining was used to evaluate the area of cerebral infarction;Western-Blot was used to determine the content of HPSE,SDC-1,Tie-2,TNF-?,NF-?B protein in brain tissue;Elisa method to detect the concentration of SOD and MDA in the core area of cerebral infarction and the concentration of TNF-?and IL-6 in the serum;immunofluorescence staining and confocal microscopy analysis of macrophage infiltration in the core area of cerebral infarction.Results1.TTC staining and behavioral test results:compared with the R group,the infarct volume in the RD group was significantly reduced(p<0.05),and the neurological impairment was significantly improved(p<0.01).Behavioral results suggested that there was no significant difference between the SD group and the S group(p>,0.05).Compared with group S,the activity time(p<0.01)and the activity distance(p<0.001)of group R were significantly reduced.Compared with the SD group,the activity time(p<0.01)and the activity distance(p<0.01)of the RD group were also significantly reduced.Compared with R group,the activity time(p<0.05)and the activity distance(p<0.01)in RD group were significantly increased.2.Western-Blot analysis of HPSE,SDC-1,Tie-2 results:Compared with the S group,there was no significant difference in the expression of all protein contents in the SD group(p>0.05).Compared with the S group,the contents of HPSE,TNF-? and NF-?B were significantly increased(p<0.01),while the contents of SDC-1(p<0.001)and Tie-2(p<0.01)were significantly reduced in the SD group.Compared with the R group,HPSE(p<0.01),TNF-p<0.001,NF-B(p<0.001)were significantly reduced in the RD group,while sdc-1 and tie-2 were significantly reduced in the RD group(p<0.001).3.Elisa detected the content of TNF-? and IL-6 in peripheral serum:There was no significant difference between the S group and the SD group(p>0.05).Compared with the S group,the content of TNF-? and IL-6 in the R group were significantly increased(p<0.01)in the R group;compared with the SD group,the content of TNF-?(p<0.05)and IL-6(p<0.01)also increased significantly in the RD group.Compared with the R group,the levels of TNF-? and IL-6 in the peripheral blood of the RD group were significantly reduced(p<0.01)in the RD group.4.Elisa detected the content of SOD and MDA in cerebral infarction tissues:There were no significant differences in the content of SOD and MDA between the S and SD groups.Compared with the S group,the content of MDA increased significantly(p<0.01),while the content of SOD decreased significantly(p<0.01)in the R group.Compared with SD group,the content of MDA in RD group was significantly increased(p<0.05),while the content of SOD was significantly reduced(p<0.05).Compared with the R group,the MDA content in the peripheral serum of the RD group will decrease to some extent(p<0.05),while the SOD content will increase to some extent(p<0.05).5.Immunofluorescence detection of macrophage infiltration in the core area of cerebral infarction:Compared with the R group,the degree of macrophage infiltration was significantly reduced in the RD group.Dexmedetomidine can significantly reduce macrophage infiltration in the core area of cerebral infarction after cerebral ischemia-reperfusion injury(p<0.05).Conclusion1.Dexmedetomidine pretreatment protects brain tissue by reducing cerebral ischemia-reperfusion injury to vascular endothelial glycocalyx.2.Dexmedetomidine can reduce the production of inflammatory factors TNF-?and NF?B,inhibit the production of glycocalyx damage markers HPSE,and activate SDC-1,Tie-2,which reduces the degradation of glycocalyx in vascular endothelial caused by cerebral ischemia reperfusion injury.3.Dexmedetomidine can reduce the levels of TNF-? and IL-6 inserum after CIRI.4.Dexmedetomidine pretreatment can increase SOD activity and reduce MDA content in brain tissue,which reduces oxidative stress response after CIRI.5.Dexmedetomidine can reduce the infiltration of macrophages in the infarction core after CIRI.