p38MAPK、NF-κB、ICAM-1在SAH后CVS中的作用机制

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目的探讨兔蛛网膜下腔出血(SAH)后丝裂原活化蛋白激酶p38(p38MAPK)、核转录因子-κB(NF-κB)及细胞间黏附分子-1(ICAM-1)在脑血管痉挛(CVS)发病机制中相互间内在联系。方法新西兰纯种健康级大白兔40只,随机分为对照组、ICAM-1单克隆抗体治疗组、NF-κB拮抗剂治疗组、p38MAPK抑制组,每组10只。枕大池二次注血制作兔SAH后CVS模型。分离兔基底动脉(BA),应用形态学观察、免疫组化和原位杂交等方法,观测兔BA管径、血管壁上p38MAPK、NF-κB及ICAM-1表达变化及其相互间关系。结果对照组血管造影出现管腔狭窄,而各治疗组未见明显血管狭窄。免疫组化显示对照组p38MAPK、NF-κB、ICAM-1在内膜、中膜有强烈的表达;p38MAPK抑制组p38MAPK、NF-κB、ICAM-1的表达主要局限在内膜、内膜下,表达微弱;NF-kB拮抗剂治疗组p38MAPK、NF-κB、ICAM-1在内膜和内膜下也有微弱表达,而p38MAPK在中膜也出现表达;ICAM-1单克隆抗体治疗组p38MAPK、NF-κB在内膜、中膜均有表达,ICAM-1仅在内膜和内膜下有微弱表达。原位杂交结果与免疫组化类似。结论在兔BA血管壁上存在着由p38MAPK、NF-κB调控、ICAM-1介导的痉挛血管壁炎症反应,这一级联反应在CVS的发生、发展过程中起了重要的作用。 Objective To investigate the expression of p38MAPK, NF-κB and ICAM-1 in cerebral vasospasm after subarachnoid hemorrhage (SAH) in rabbits CVS) pathogenesis of mutual relations between the internal. Methods Forty New Zealand purebred healthy rabbits were randomly divided into control group, ICAM-1 monoclonal antibody treatment group, NF-κB antagonist treatment group and p38MAPK inhibition group, with 10 rats in each group. CVS model of rabbits with SAH produced by secondary injection of occipital large pool. Rabbit basilar artery (BA) was isolated and morphological observation, immunohistochemistry and in situ hybridization were used to observe the changes of BA diameter, p38MAPK, NF-κB and ICAM-1 expression and their relationship with each other. Results The control group showed stenosis of angiogram, but no obvious vascular stenosis was found in each treatment group. Immunohistochemistry showed that p38MAPK, NF-κB and ICAM-1 in the control group were strongly expressed in the intima and media; the expression of p38MAPK, NF-κB and ICAM-1 in the p38MAPK inhibition group was mainly confined to the intima, P38MAPK, NF-κB and ICAM-1 were weakly expressed in the intima and intima of the NF-κB antagonist group, while p38MAPK was also expressed in the medial membrane. ICAM-1 monoclonal antibody treatment group, p38MAPK, NF -κB expression in the intima and media, ICAM-1 only weakly expressed in the intima and intima. In situ hybridization results and immunohistochemistry similar. Conclusions There are p38MAPK, NF-κB regulatory and vascular wall inflammatory responses induced by ICAM-1 in rabbits BA. This cascade plays an important role in the occurrence and development of CVS.
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