【作者】 董靖德；

【导师】 石静萍；

【作者基本信息】 南京医科大学 ， 神经病学， 2008， 硕士

【摘要】 目的:研究厄贝沙坦预处理对缺血再灌注大鼠脑和血清ICAM-1与VCAM-1水平的动态变化,探讨厄贝沙坦对脑缺血再灌注损伤后炎症反应的影响和脑保护作用。方法:健康雄性SD大鼠随机分为假手术组、缺血再灌注组和厄贝沙坦缺血再灌注组。线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,厄贝沙坦缺血再灌注组动物于MCAO前3周给予灌胃新鲜配置成的厄贝沙坦混悬液(6mg/ml,30mg/kg),同时缺血再灌注组以及假手术组给予安慰剂(生理盐水,5ml/kg)灌胃3周。缺血再灌注24h和72h进行神经功能评分,后处死动物,TTC染色测梗死体积百分比。用免疫组化法半定量检测梗死半球缺血带的ICAM-1和VCAM-1的表达。用ELISA法测定血清中sICAM-1和sVCAM-1的表达。结果:(1)厄贝沙坦缺血再灌注组神经行为学评分为1.30±0.48(24h)和1.40±0.52(72h),与缺血再灌注组比较,厄贝沙坦能够显著的改善大鼠局灶性脑缺血再灌注后24h和72h的神经功能(均p＜0.01)。(2)厄贝沙坦缺血再灌注组梗死体积百分比为31.7±8.47%(24h)和45.48±5.93%(72h),与缺血再灌注组相比,无论缺血再灌注24h还是72h,其梗死面积均明显小于缺血再灌注组(均p＜0.01)。(3)厄贝沙坦缺血再灌注组再灌注后214h和72h后的脑内ICAM-1、VCAM-1蛋白的表达和缺血再灌注组相比,缺血再灌注24h和72h均显著降低(p＜0.05)。(4)厄贝沙坦缺血再灌注组再灌注后:24h和72h后sICAM-1水平、sVCAM-1水平均明显低于缺血再灌注(p＜0.05)。缺血再灌注组和厄贝沙坦缺血再灌注组sICAM-1、sVCAM-1表达水平均明显高于假手术组的表达水平(p＜0.01)。(5)Pearson相关性显示ICAM-1和sICAM-1有显著正相关性的(p＜0.05),VCAM-1、sVCAM-1也具有显著的正相关性(p＜0.05)。sICAM-1、sVCAM-1与梗死面积也具有正相关性(p＜0.05)。sICAM-1、sVCAM-1水平反映了缺血再灌注的损伤程度。结论:厄贝沙坦可以降低中枢及外周粘附分子的表达,减少梗死体积,改善神经功能,对脑缺血再灌注起保护作用。更多还原

【Abstract】 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.更多还原