尼莫地平抑制缺血再灌注后成年大鼠脑内神经发生  

Nimodipine inhibits ischemia-reperfusion triggered neurogenesis in adult rats

作　　者：田和平[1] 顾斌[1] 程峰[1] 郝怀勇[1] 胡卫星[1] 李立新[1] 

机构地区：[1]南京医科大学第一附属医院神经外科

出　　处：《中国临床药理学与治疗学》2009年第1期32-37,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省"兴卫工程"医学重点人才项目(RC2007062)

摘　　要：目的:观察尼莫地平(Nimodipine)对大鼠脑缺血再灌注后海马齿状回神经发生的影响并探讨其相关机制。方法:采用四动脉阻断法诱导大鼠全脑缺血,缺血20 min前腹腔内注射尼莫地平或脑室内注射细胞外信号调节激酶(extracellular sig-nal-regulated kinase,ERK)的抑制剂U0126;免疫组化Brdu标记法检测脑内海马神经发生;WesternBlot法检测海马组织ERK、磷酸化ERK(p-ERK)蛋白的表达。结果:尼莫地平抑制脑缺血再灌注后海马部位的神经发生的同时也抑制了脑缺血再灌注后海马齿状回p-ERK的表达;海马部位神经发生在U0126组与U0126+尼莫地平联合给药组差异无统计学意义。结论:尼莫地平显著抑制脑缺血再灌注后海马齿状回的神经发生,其机制与下调p-ERK表达密切相关。AIM： To observe the effects of Nimodipine on hippocampal dentate gyms neurogenesis of the adult rat triggered by ischemia-reperfusion and investigate its molecular mechanism. METHODS： The cerebral ischemia-reperfusion models were established by four-vessel-blocked method. Nimodipine or the extracellular signal-regulated kinase inhibitor U0126 was administrated by intravenous injection or intraventricular injection, respectively before ischemia 20 min. The hippocampal dentate gyms neurogenesis was detected by immunohistochemistry of 5-bromodeoxyuridine （Br- du）. The expressions of ERK and p-ERK were detected by Western blotting. RESULTS： Nimodipine not only inhibited hippocampal dentate gyms neurogenesis but also the expression of p-ERK in the area of dentate gyms after ischemia-reperfusion. There was no significant difference in hippocampal dentate gyms neurogenesis between the U0126 group and U0126 combined with Nimodipine group. CONCLUSION： Nimodipine inhibits hippocampal dentate gyms neurogenesis, and it may be related with the down-regulation p-ERK after ischemia- reperfusion.

关 键 词：脑缺血 神经发生 尼莫地平 细胞外信号调节激酶 

分 类 号：R966[医药卫生—药理学]