摘要
目的探讨辛伐他汀对兔蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)中炎性反应的影响。方法 36只新西兰大白兔随机分为3组,每组12只。①对照组:给予常规饲养并枕大池二次注入等渗盐水;②SAH组:通过枕大池二次注血法建立SAH模型;③SAH+辛伐他汀组:对SAH兔经胃灌注辛伐他汀5 mg·kg^(-1)·d^(-1),连续7 d。在各组兔造模前后,行两次脑血管造影。第2次脑血管造影后1 d,取基底动脉组织制作病理切片,分别于光镜和透射电镜下观察其显微及超微结构。行免疫荧光染色后,采用共聚焦显微镜观察基底动脉内皮细胞核转录因子-κB(NF-κB)表达量的变化,同时采用实时荧光定量PCR技术检测其细胞间黏附分子1(ICAM-1)mRNA的表达。结果①脑血管造影显示二次注血后,SAH组兔基底动脉出现明显的痉挛,管径变细,SAH组的管径为(0.68±0.09)mm,对照组为(0.87±0.06)mm,P<0.05;而给予辛伐他汀后,痉挛减轻,SAH+辛伐他汀组的管径为(0.77±0.08)mm,与SAH组管径比较,P<0.05。SAH组兔基底动脉壁略有增厚,电镜显示平滑肌细胞内合成旺盛;而给予辛伐他汀预处理后,这些变化明显减轻。②SAH组兔基底动脉管壁内皮细胞内NF-κB表达高于对照组(156±9和84±8,P<0.05),而给予辛伐他汀后,NF-κB表达量降低(118±9),与SAH组比较,P<0.05。SAH组兔基底动脉组织ICAM-1 mRNA的表达量高于对照组(0.843±0.029和O.673±0.011,P<0.05);给予辛伐他汀后,基底动脉ICAM-1 mRNA的表达量低于SAH组(0.763±0.037),与SAH组比较,P<0.05。结论辛伐他汀可能通过抑制炎性反应从而预防SAH后CVS的发生,其抑制炎性反应,可能是通过NF-κB信号途径实现的。
Objective To investigate the effect of simvastatin on inflammatory reactions in cerebral vasospasm （CVS） after subarachnoid hemorrhage （SAH） in rabbits. Methods Thirty-six New Zealand white rabbits were randomly allocated into three groups： Control, SAH and simvastatin groups （n = 12 in each group）. The conventional feeding were given and isotonic saline solution was injected into cisterna magna twice in the control group. The SAH model was induced by injection of autologons blood into the cisterna magna twice in the SAH group; and simvastatin 5 mg · kg^- 1 · d^- 1 was infused into stomach for 7 days in the simvastatin group. Cerebral angiography was performed twice before and after inducing the rabbit model in each group. One day after the second cerebral angiography, the basilar artery specimens were taken for the pathological examination. Their micro and uhramicrostructures were observed under a light microscope and transmission electron microscope. Confocal immunofluorescence microscopy was used to detect the changes of nuclear transcription factor-κB （NF-κB） expression in basilar artery endothelial cells, and the real-time PCR assay was used to detect the changes of intercellular adhesion molecule-1 （ ICAM-1 ） mRNA expression. Results （1）Obvious spasms of the rabbit basilar arteries after the second injection of blood were visualized through cerebral angiography, and the arterial diameters became thinner （0.68 ± 0. 09 mm in the SAH group, and 0.87 ± 0.06 mm in the control group, P 〈 0. 05 ） ; The vasospasm was relieved by administration of simvastatin （0.77 ± 0.08 mm in the simvastatin group, and 0.68 ± 0.09 mm in the SAH group, P 〈 0.05 ）. The thickness of the basilar artery walls increased slightly in the SAH group. Electron microscopy showed that the synthesis was vigorous in the smooth muscle ceils; and these changes were significantly reduced after pretreatment with simvastatin. （2）The expression of NF-κB in rabbit basilar artery endothelial cells in th
出处
《中国脑血管病杂志》
CAS
2009年第8期413-418,共6页
Chinese Journal of Cerebrovascular Diseases
基金
教育部博士点新教师基金资助项目(20070001770)
关键词
蛛网膜下腔出血
血管痉挛
颅内
炎症
反应抑制
兔
辛伐他汀
Subarachnoid hemorrhage
Vasospasm, intracranial
Inflammation
Reactive inhibition
Rabbits
Simvastatin
