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目的观察兔蛛网膜下腔出血(subarachnoid hemorrhage,SAH)模型基底动脉中核转录因子(nuclear factor-κB,NF-κB)和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的时间动态表达情况,并分析NF-κB与SAH诱导的基底动脉壁增殖的关系。方法 40只雄性新西兰大白兔完全随机分为假手术组和SAH组,每组20只,每组各分为术后1、4、7、14d亚组(n=5)。SAH组采用枕大池二次注血法建立脑血管痉挛动物模型,假手术组注入等量生理盐水,各组于二次注血术后第1、4、7、14天观察基底动脉组织病理学改变,并应用免疫组化、Western blot法分析各组基底动脉中NF-κB、PCNA阳性细胞比值和蛋白水平表达的差异。结果与假手术组相比,SAH组基底动脉血管壁平滑肌随观察时间逐渐增厚,管腔狭窄,在第7天达高峰(P<0.05),在第14天时恢复至正常水平;NF-κB和PCNA蛋白表达随时间逐渐增强,在第7天达高峰(P<0.05),在第14天时表达下降。NF-κB的表达与基底动脉平滑肌厚度变化及PCNA表达变化呈显著正相关(r=0.80、r=0.75,P<0.05)。结论NF-κB的激活可能参与了SAH后脑血管平滑肌细胞增殖,NF-κB可能通过转录多种促血管增殖因子参与SAH诱导的血管壁增殖过程。
Objective To observe the time dynamic expression of nuclear factor-κB (NF-κB) and proliferating cell nuclear antigen (PCNA) in basilar artery of subarachnoid hemorrhage (SAH) model in rabbits. Relationship between NF-κB and SAH-induced proliferation of basilar artery wall. Methods Forty male New Zealand white rabbits were randomly divided into sham operation group and SAH group, with 20 rats in each group. Each group was divided into subgroups (n = 5) on the 1st, 4th, 7th and 14th day after operation. In the SAH group, cerebral vasospasm was induced by the second injection of occipital cistern and the rats in the sham-operated group were injected with the same amount of saline. The basal arterial histopathology was observed on the 1st, 4th, 7th and 14th day after the secondary injection The changes of NF-κB and PCNA positive cells in basilar artery of each group were analyzed by immunohistochemistry and Western blot. Results Compared with the sham operation group, the smooth muscle in the basilar artery wall of SAH group was thicker and the lumen was stenotic and reached its peak on the 7th day (P <0.05), and returned to the normal level on the 14th day. NF-κB And PCNA protein expression gradually increased over time, reached the peak on the 7th day (P <0.05), and decreased on the 14th day. The expression of NF-κB was positively correlated with the thickness of basilar artery smooth muscle and the expression of PCNA (r = 0.80, r = 0.75, P <0.05). Conclusion The activation of NF-κB may be involved in the proliferation of cerebrovascular smooth muscle cells after SAH. NF-κB may be involved in SAH-induced proliferation of vascular wall by transcription of a variety of pro-angiogenic factors.