SAH后迟发性脑血管痉挛中ICAM-1的表达变化及ICAM-1单克隆抗体和甲基强的松龙的防治作用

Expression of ICAM-1 in delayed cerebral vasospasm after subarachnoid hemorrhage and preventive and therapeutic effect of monoclonal antibody against ICAM-1 and methylprednisolone

目的检测自发性蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(DCVS)动脉中内皮细胞间粘附分子-1(ICAM-1)表达变化,同时评价ICAM-1单克隆抗体和甲基强的松龙的防治效果。方法中国白兔48只,体重2～2.5kg,随机分为四组。A组:正常对照组(n=8),不做枕大池穿刺注血,Day0处死;B组:SAH组(n=24),采用枕大池二次注血SAH模型,即在Day0和Day2第一、二次枕大池注血,并分别在Day4、Day7和Day14分三批处死,每批8只;C组:SAH+ICAM-1单克隆抗体和甲基强的松龙组(n=8),枕大池注射ICAM-1单克隆抗体10μg,耳缘静脉注射甲基强的松龙30mg/kg,并在Day7处死;D组:SAH+生理盐水组(n=8),用等量37℃生理盐水代替ICAM-1单克隆抗体和甲基强的松龙,第一次注血后Day7处死。结果A组动物基底动脉组织结构正常。B组动物基底动脉在Day4、Day7时出现血管痉挛,Day7时最严重,Day14时血管痉挛缓解。C组动物基底动脉痉挛明显缓解(P<0.05)。而D组动物基底动脉脑血管痉挛无缓解。B组动物基底动脉壁ICAM-1表达于day4开始增加,day7达到高峰,day14降至正常水平。C组ICAM-1表达明显减弱,与B组(day7)和D组比较有显著差异(P<0.01)。结论在兔SAH后迟发性脑血管痉挛中ICAM-1表达变化与DCVS炎症反应时相一致。应用ICAM-1单克隆抗体和甲基强的松龙,可抑制炎症反应的启动和进展,减轻炎症反应从而缓解DCVS。

Objective To examine the expression of ICAM-1 in the basiar artery（BA）with delayed cerebral vasospasm after subarachnoid hemorrhage and assess the preventive effect of monoclonal antibody against ICAM-1 and Methylprednisolone.Methods Forty-eight chinese rabbits（weight range from 2kg to 2.5kg）were randomly divided into four groups.A group：control group,animals served as controls and were not injected to SAH（n=8）.B group：SAH group（n=8）,We used the two-hemorrage model of SAH,and injecting autologous arterial blood into the cisterna magna at day 0 and day 2.Twenty-four animals in SAH group were killed respectively at day 4,day 7,and day 14.C group：SAH ＋ monoclonal antibody against ICAM-1 and Methylprednisolone group（n=24）.In this group monoclonal antibody against ICAM-1 and Methylprednisolone was applied and animals were killed at day 7 after SAH.D group：SAH＋saline group（n=8）.Same volume 37℃ physiological saline was applied and animals were killed at day 7 after SAH.Results The structure of basilar artery is normal in A group.The vasopasm of BA was found in the SAH group at day4 and day 7,especially at day 7.It was disappeared at day 14.The vasopasm of BA was alleviated in the animals of C group but not in D group.The expression of ICAM-1 in the BA of B group animals began to increase at day 4,summit at day 7,decline to normal level at day 14.The expression was remarkably remitted in C group animals compared with that in B group（day 7）and D group（P0.01）Conclusion The pattern of expression levels of ICAM-1 fits remarkably well with time course of inflammation of delayed cerebral vasospasm.Monoclonal antibody against ICAM-1 and Methylprednisolone can relieve the inflammation and allay delayed cerebral vasospasm by inhibiting the initiate and progression of inflammation.