Rho激酶抑制剂对大鼠脑缺血再灌注后核转录因子和新型趋化因子表达的影响

摘要

目的 探讨Rho激酶抑制剂法舒地尔对大鼠脑缺血再灌注损伤后的保护作用及可能机制.方法 健康成年雄性SD大鼠90只,随机分为3组:假手术组、模型组、法舒地尔组,每组30只,每组再按照再灌注时间不同分为6、1 2、24 h3个时间点,每个时间点10只,线栓法制作大鼠大脑中动脉缺血再灌注损伤模型.术后对大鼠进行神经功能评分,RT-PCR检测缺血侧脑组织中新型趋化因子mRNA、NF-κB p65 mRNA表达.结果 与假手术组比较,模型组和法舒地尔组大鼠脑缺血再灌注6、12、24 h NF-κB p65 mRNA、新型趋化因子mRNA表达明显升高,差异有统计学意义(P＜0.05)；与模型组比较,法舒地尔组大鼠脑缺血再灌注6、12、24 h神经功能缺损评分明显降低,12、24 h NF-κB p65 mRNA、新型趋化因子mRNA表达明显降低,差异有统计学意义(P＜0.05,P＜0.01).结论 法舒地尔的脑保护作用可能与其减轻大鼠脑缺血再灌注损伤后的炎性反应有关.%Objective To study the role of Rho kinase inhibitor(fasudil) in protection of rat myocardium against cerebeal ischemia reperfusion injury and its possible mechanism. Methods Ninety adult healthy male SD rats were randomly divided into sham operation group,model group,and fa-sudil group(30 in each group). Rats in each group were further divided into 6 h reperfusion group?2 h reperfusion group and 24 h reperfusion groupdO in each group). A rat middle cerebral artery ischemia reperfusion model was established with thread embolism. Nerve function in rats was scored after operation. Levels of novel chemotactic factor mRNA and NF-kB p65 mRNA in is-chemic brain tissues were measured by RT-PCR. Results The expression levels of NF-kB p65 mRNA and novel chemotactiv factor mRNA were significantly higher in model group, fasudil group,6 h reperfusion group, 12 h reperfusion group and 24 h reperfusion group than in sham operation group(P<0. 05). The score of nerve function and the expression level of NF-kB p65 mRNA and novel chemotactic factor mRNA were significantly lower in fasudil group,6 h reperfusion group, 12 h reperfusion group and 24 h reperfusion group than in model group(P<0. 05). Conclusion The role of fasudil in protection of rats agaist cerebral ischemia reperfusion injury is related with the alleviated inflammatory reaction.