复方蒲黄颗粒对脑缺血再灌注大鼠GAP-43表达的影响及动态变化规律

摘要

[目的]通过观察大脑缺血再灌注大鼠模型治疗前、后神经生长相关蛋白(growth associated protein 43,GAP-43)的表达和动态变化规律,探讨复方蒲黄颗粒对脑缺血再灌注后神经保护作用机制.[方法]用复方蒲黄颗粒大、中、小剂量组分别干预局灶性脑缺血再灌注大鼠模型,于缺血再灌注1、3、7、14、21d这5个时间点断头取脑组织,免疫组化检测GAP-43的含量.[结果]模型组GAP-43的表达在再灌注1d就显著升高,7d达到高峰,14d开始下降,但均高于假手术组(P＜0.05),21d的GAP-43表达逐渐下降(P＞0.05).复方蒲黄颗粒大、中剂量干预组中大鼠脑组织的GAP-43表达在缺血再灌注后1d、3d、7d、14d明显升高(p＜0.05),再灌注21d时GAP-43的表达升高不明显(P＞0.05).[结论]复方蒲黄颗粒的神经保护作用机制可能与上调GAP-43表达有关.大脑缺血再灌注可使GAP-43表达增加,7d可能为治疗的关键时间窗.%[Objective]To investigate the effects of puhuang granule on neural unctional recovery following focal cerebral ischemia-reperfusion in rats by exploring the expression change regularity of growth associated protein (GAP-43). [Method]Totally SD rats were randomized into sham operation(sham) group; ischemia/reperrusion(I/R)group; puhuang granule of high dose(PHH); medium dose(PHM)group; low dose(PHL)group. The rats were surgically prepared for the middle cerebral artery occlusion(MACO) according to the technique of Zea-Longa, etc. Reperfusion was conducted at 2h after ischemia, according to different reperfusion time, and at Id, 3d, Id, 14d, 21d after reperfusion the rats were decaoitated. Exploring the expression change regularity of GAP-43 was detected by using immunohistochemistry assay. [Result] Compared with sham group, the expression of GAP-43 was increased at 1d after reperfusion. The peak expression appeared within 7d and decreased from 7d to 14d arter reperfusion, but remained high level. The expression of GAP-43 was close to the normal level at 21d after reperfusion. The number of GAP-43 imunoreactive cells at Id, 3d, 7d, 14d after reperfusion in PHH and PHM group increased compared with the sham group. The number of GAP-43 imunoreactive cells changed unobviously at 21d after reperfusion in PHH and PHM groups. [Conclusion] The expression of GAP-43 was increased at 1d after reperfusion in rats and the peak expression appeared showed 7d after reperfusion was critical time for treatment. Inhibiting the excessive expression of GAP-43 might be the mechanism of the protective effect of Puhuang granule in rat brain following focal cerebral ischemia-reperfusion.