Anti-inflammatory Effect Of Irbesartan On Focal Brain Ischemia/reperfusion Injury In Rats

Objective:To investigate the anti-inflammatory effect of pretreatment with AT1 receptor antagonist,Irbesartan on brain and peripheral blood of the rats in focal brain ischemia-reperfusioln injury.Methods:Male SD rats were randomly assigned to sham operated group,ischemia/reperfusion group and Irbesartan ischemia-reperfusion group. Pretreatment with Irbesartan(6mg/ml,30mg/kg)for 3 weeks in Irbesartan ischemia-reperfusion group and pretreatment with saline (5ml/kg)for 3 weeks in both ischemia-reperfusion group and sham operated group before operation,we applied MCAO model of Longa, after 24 hours and 72 hours reperfusion following 90 minutes of cerebral ischemia,cerebral infarct size was measured by TTC,adhesion molecules in brain and peripheral blood were detected by ELISA and immunohistochemical technique.Result:(1)The scores of the Irbesartan ischemia-reperfusion group were 1.30±0.48(24h)and 1.40±0.52(72h).There were significant differences on the neurological impairment scores between the Irbesartan ischemia-reperfusion group and the ischemia-reperfusion group at 24h and 72h(all p＜0.01). (2)The infarct volume percentage of the Irbesartan ischemia-reperfusion group were 31.7±8.47%(24h)and 45.48±5.93%(72h).The infarct volume was significantly reduced in the Irbesartan ischemia-reperfusion group compared with the ischemia-reperfusion group(all p＜0.01).(3)The level of ICAM-1 and VCAM-1 were significantly decreased in the Irbesartan ischemia-reperfusion group compared with the ischemia/reperfusion group(p＜0.05).(4)The level of sICAM-1 and sVCAM-1 were significantly decreased in the Irbesartan ischemia-reperfusion group compared with the ischemia-reperfusion group(p＜0.05).The level of sICAM-1 and sVCAM-1 were significantly increased in both the Irbesartan ischemia-reperfusion group and ischemia-reperfusion group compared with sham group(p＜0.01).(5)Correlation analysis:The change between ICAM-1,VCAM-1 in brain and sICAM-1,sVCAM-1 in peripheral blood is positive correlation(r=p＜0.05=.The change of the infarct sizes is positive correlation with sICAM-1,sVCAM-1(all p＜0.05).The levels of sICAM-1,sVCAM-1 could imply the degree of severity of ischemia-reperfusion injury.Conclusion:Pretreatment with AT1 receptor antagonist might protect brain from ischemia-reperfusion injury in rats by inhibiting leukocyteendothelial cell adhesion and decreasing cerebral infarct sizes.