培高利特对脑缺血-再灌注损伤海马神经元HIF-1 α表达的影响.docVIP

培高利特对脑缺血/再灌注损伤海马神经元HIF-1 α表达的影响 作者：纵雪梅 , 许铁, 曾因明，裴冬生 【摘要】 目的 研究培高利特(pergolide)对沙土鼠前脑脑缺血/再灌注(I/R)损伤海马CA1区神经元低氧诱导因子-1α(hypoxia-inducible factor-1 α, HIF-1 α)表达的影响。方法 采用沙土鼠5 min I/R损伤模型。54只雄性沙土鼠随机分为3组：假手术组、I/R组、培高利特组。分别于再灌注第1、3、7天行免疫组织化学染色法，检测海马CA1区神经元HIF-1 α的表达。结果 假手术组沙土鼠海马CA1区HIF-1 α有较弱的表达。与假手术组相比，I/R组海马CA1区再灌注1天HIF-1 α的表达无明显改变(P0.05);至再灌注3天及7天HIF-1 α表达消失(P0.01或P0.05)。培高利特可显著诱导海马CA1区神经元中HIF-1 α的表达，以再灌注1天表达最多(P0.01)，随再灌注时间的延长表达缓慢减少，至第7天仍有较高水平的表达(P0.01)。结论 培高利特可显著诱导脑I/R损伤后海马CA1区神经元HIF-1 α的表达，可能是其脑保护作用的机制之一。 【关键词】 脑缺血/再灌注损伤;培高利特;c-jun;神经元低氧诱导因子-1α;沙土鼠 　　Abstract: Objective To investigate the effects of pergolide on the expression of HIF-1α in hippocampal CA1 region folloEing transient forbrain ischemia/reperfusion (I/R) injury in gerbils. Methods Gerbil forebrain ischemia was induced by occlusion of bilateral carotid arteries for 5 min. 54 gerbils were randomly divided into sham group, I/R group and pergolide group. Immunohistochemistry was used to determine the expression of HIF-1α in hippocampal CA1 region on days 1, 3 and 7 after ischemia. Results There was a weak expression of HIF-1α in the sham group. In I/R group the expression did not have any evident change 1 day after ischemia but disappeared thoroughly 3 and 7 days after ischemia (P0.01 or P0.05). Pretreatment with pergolide could significantly induce the expression of HIF-1α. The expression of HIF-1 α reached its peak on day 1 and thereafter gradually decreased. The expression was still high on the 7th day after ischemia (P0.01). Conclusion All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis by inducing the expression of HIF-1α. 　　Key words: cerebral ischemia/reperfusion injury; pergolide; c-jun; hypoxia-inducible factor-1α; gerbil 　　缺血性脑病发病率很高，给社会和家庭造成极大的负担，因此脑缺血/再灌注(I/R)损伤的机制及脑保护的方法的研究具有非常重要的意义。迄今为止，脑I/R损伤的发病机制仍未完全阐明，临床 治疗 尚缺乏有效的保护策略和治疗手段。本研究旨在观察多巴胺D2受体激动剂培高利特(pergolide)对脑I/R损伤后1～7 天海马神经元HIF-1 α表达的影响，以期深入探讨其发挥脑保护作用的基因调控机制。 　　1 材料和