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Neuroprotective effect of SP600125, an inhibitor of JNK on brain ischemia/reperfusion in rats
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- Author:
- No author available
- Journal Title:
- JOURNAL OF THE FOURTH MILITARY MEDICAL UNIVERSITY
- Issue:
- 20
- DOI:
- 10.3321/j.issn:1000-2790.2007.20.005
- Key Word:
- 脑;脑缺血;再灌注损伤;细胞凋亡;JNK;XRCC1
Abstract： 目的:探讨SP600125-JNK特异性抑制剂对大鼠脑缺血再灌注神经元损伤的保护性作用及其作用机制.方法:雄性SD大鼠108只,体质量290～310 g,随机分成假手术组(SH组),缺血再灌注组(IR组),JNK抑制剂SP600125组(SP组),分别于缺血前30 min侧脑室注射10 mL/L DMSO,10mL/L DMSO及JNK抑制剂SP600125.每组根据再灌注时间分为2,6,12,24,48和72 h 6个亚组,每亚组6只动物.采用4-VO法建立SD大鼠全脑缺血模型,在预定时间点行灌注、固定、取脑、石蜡包埋切片,光镜下计数CA1区存活细胞,TUNEL法检测CA1区凋亡细胞,免疫组化检测DNA修复蛋白X线修复交叉互补蛋白1(XRCC1)的表达变化.结果:脑缺血再灌注后海马CA1区神经元存活数目SP组高于IR组(P＜0.01),凋亡细胞数目低于IR组(P＜0.01).SH组XRCC1表达量较强,IR组XRCC1的表达2 h即已开始下降,与SH组比较有统计学差异(P＜0.01).SP组XRCC1表达量的降低不明显,各时点与IR组比较均有统计学差异(P＜0.01).结论:在大鼠全脑缺血再灌注损伤过程中,SP600125-JNK特异性抑制剂对神经元起到了显著的保护性作用,其机制可能为抑制DNA修复蛋白下调的方式维护DNA修复功能,从而减少神经元的凋亡.
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