环磷酰胺对大鼠脑缺血再灌注后脑组织中ICAM-1、白细胞影响的研究

目的观察环磷酰胺对大鼠脑缺血再灌注后脑组织中ICAM-1表达、白细胞浸润的影响。方法36只雄性SD大鼠分为假手术组和脑缺血再灌注组。脑缺血再灌注组中包括环磷酰胺治疗组和生理盐水对照组,每组按脑缺血2h后再灌注2h、4h、6h、24h又分为4个亚组。脑缺血再灌注组于脑缺血2h再灌注后2h、4h、6h、24h处死动物,用免疫组织化学法观察再灌注后不同时间点脑组织中ICAM-1的表达,HE染色法观察白细胞的浸润程度。结果(1)脑缺血再灌注后,脑缺血坏死区周边ICAM-1的表达及白细胞的浸润增多,并于24h达高峰;环磷酰胺组在相同再灌注时间点的ICAM-1表达及白细胞的浸润均明显低于对照组。(2)ICAM-1的表达与白细胞的浸润呈现正相关性。结论脑缺血再灌注后,ICAM-1的表达上调,介导了白细胞和内皮细胞的粘附,参与了脑缺血再灌注损伤的过程。环磷酰胺治疗组ICAM-1的表达、白细胞的浸润均少于对照组,说明环磷酰胺有抑制粘附分子表达上调、抑制白细胞浸润的作用,因而具有神经保护的作用,为该治疗应用于临床提供了理论基础。

Effects of cyclophosphamide on the expressions of intercellular adhesion molecule-1 (ICAM-1) and leukocyte infiltration after focal cerebral ischemia reperfusion in rats

Objective To investigate the effects of cyclophosphamide on the expressions of intercellular adhesion molecule-1(ICAM-1) and leukocyte infiltration after focal cerebral ischemia reperfusion injury.Methods 36 male SD rats were randomly divided into 2 groups:false operation group and cerebral ischemia reperfusion group.The cerebral ischemia reperfusion group included control group and observing group(reperfusion for 2,4,6,24 hours post-ischemia).The rats were killed after reperfusion(2,4,6,24 hours).Immunohistochemical technique was used to examine the expression of ICAM-1.Leukocyte infiltration were measured by HE staining technique.Compare the expression of ICAM-1and leukocyte infiltration in both control group and observing group of the same time of reperfusion.Results (1)There was a significant increase in the expression of ICAM-1 and leukocyte infiltration in the ischemic brain tissue,that peaked just at the 24h of reperfusion.The expression of ICAM-1and leukocyte infiltration in cyclophosphamide-treated rats decreased more significantly than in control rats.(2)The expression of ICAM-1 was correlated with the degree of leukocyte l infiltration.Conclusions The expression of ICAM-1 and leukocyte infiltration increased after cerebral ischemia reperfusion.This indicates that ICAM-1 and leukocyte infiltration is closely associated with the neuronal damage after cerebral ischemia reperfusion.Cyclophosphamid might inhibit the expression of ICAM-1 and the mechanism it might protect the nerve tissue.