缺氧缺血后脑皮质细胞间黏附分子-1蛋白的表达及意义

Expression of intercellular adhesion molecule-1 protein in cerebral cortex after hypoxic-ischemic damage and its significance

目的:探讨新生大鼠缺氧缺血脑损伤后皮质区细胞间黏附分子-1(ICAM-1)蛋白的表达及辛伐他汀的干预作用。方法:选用144只7日龄SD大鼠,随机分为假手术组、生理盐水组、胞二磷胆碱组、辛伐他汀组,每组又分为0、12、24、48、72 h和7天6个时间点,每个时间点6只,按R ice方法,制作成H IBD模型后,各组分别于即刻及之后的每天同一时刻进行不同的干预,假手术组仅手术游离左侧颈总动脉但不结扎,不再进行缺氧及药物干预等处理。于不同时间点剥取结扎侧脑皮质,免疫组化检测结扎侧脑皮质ICAM-1蛋白的表达,并比较各组之间的差别。结果:阴性对照组未见ICAM-1表达阳性的微血管,假手术组结扎侧皮质区ICAM-1蛋白阳性率均较低,各时间点皮质部位ICAM-1蛋白的表达差异无统计学意义(F=2.434,P>0.05)。生理盐水组、胞二磷胆碱组和辛伐他汀组ICAM-1蛋白表达阳性血管数于缺氧缺血后12 h时开始显著升高,24 h达高峰,然后开始回落,到7天时,生理盐水组和胞二磷胆碱组ICAM-1蛋白表达阳性血管数仍然显著高于假手术组(P<0.01),胞二磷胆碱组、辛伐他汀组于12、24、48、72 h时显著低于生理盐水组,7天时,辛伐他汀组已接近假手术组水平(P>0.05),且72 h、7天时,辛伐他汀组ICAM-1蛋白的表达显著低于胞二磷胆碱组(P<0.05和P<0.01)。结论:辛伐他汀和胞二磷胆碱对新生大鼠缺氧缺血脑损伤有保护作用,机制可能与其调控ICAM-1有关,且辛伐他汀的调控作用更强。

Objective：To explore the expression of intercellular adhesion molecule-1（ICAM-1） protein in cerebral cortex of neonatal rats after hypoxic-ischemic brain damage（HIBD） and the intervention effect of simvastatin.Methods：144 SD rats of 7-day-old were selected randomly and divided into sham operation group,normal saline group,citicoline group and simvastatin group,6 time points subgroups（0,12,24,48,72 hours and 7 days） were included into each group,6 rats in each subgroup,HIBD models were constructed by Rice method,and intervention measures were conducted in each subgroups at the same time,the left common carotid artery of sham operation group were dissociated without ligation,the rats in sham operation group did not receive any other treatments;the cerebral cortex of ligation side were removed and ligated at different time points,immunohistochemical method was used to detect the expression of ICAM-1 at ligation side,and the results were compared among different subgroups.Results：ICAM-1 did not express in normal saline group,the expression rate of ICAM-1 protein in cerebral cortex of ligation side in sham operation group was low,there was no significant difference among different subgroups（F=2.434,P〉0.05）;the expression levels of ICAM-1 protein in normal saline group,citicoline group and simvastatin group increased significantly at 12 hours after HIBD,achieved peak at 24 hours,then decreased;at 7 days after HIBD,the positive rates of ICAM-1 protein in normal saline group and citicoline group were significantly higher than that in sham operation group（P〈0.01）;at 12,24,48 and 72 hours after HIBD,the positive rate of ICAM-1 protein in simvastatin group was significantly lower than that in normal saline group;at 7 days after HIBD,there was no significant difference between simvastatin group and sham operation group（P〉0.05）;at 72 hours and 7 days,the positive rates of ICAM-1 protein in simvastatin group were significantly lower than those in citicoline group（P〈0.05 or P〈0.01）.Conclusion：Simvastatin and citicoline play protective effects in rats with HIBD,the mechanism is related to regulation of ICAM-1,and the regulative effect of simvastatin is superior to citicoline.