黄体酮防治大鼠缺血再灌注脑损伤中细胞凋亡及p53蛋白的变化

摘要/Abstract

摘要： 目的: 探讨黄体酮对缺血再灌注损伤脑的保护机制。方法: 采用SD 大鼠局灶性脑缺血再灌注模型(transient middle cerebral artery occlusion,MCAO),将大鼠随机分为6 组:假手术组、缺血再灌注组、二甲基亚砜溶剂(dimethyl sulfoxide, DMSO) 对照组、黄体酮(progesterone, PROG) 预防组、PROG 治疗组、PROG 预防治疗组, 应用免疫组织化学和细胞死亡原位末端标记(Insitu end labeling, ISEL) 法研究脑组织细胞凋亡及凋亡相关蛋白p53 的表达情况。结果: 高倍视野下p53 蛋白阳性细胞数, 各药物处理组凋亡细胞数与缺血再灌注组和对照组之间差异有显著的统计学意义(P <0.05)。结论: PROG 可减轻局灶性缺血再灌流脑损伤, 减少大鼠脑缺血再灌注后的脑细胞凋亡。抑制脑神经细胞中p53 蛋白表达可能是其发挥保护作用的分子机制之一。

关键词: 黄体酮, 脑缺血, 再灌注损伤, 凋亡, p53

Abstract: AIM: To study the neuroprotective effect and molecular mechanism of progesterone on reperfusion injury following ischemia.METHODS: The rats with transient middle cerebral artery occlusion (MACO) was described by Zea-longa for 2 h and reperfusion for 24 h. 48 male rats were divided randomly into 6 groups that were the sham, ischmia/reperfusion (I/R), dimethl sulfoxide (DMSO), and posttreatment, pretreatment, pre + posttreament with PROG groups.The immunohistochemistry staining and TUNEL reaction were used to facilitate the quantities of p53 protein and apoptosis in the brain tissuses.RESULTS: There were 26.25±3.54 cells in p53 immunostaining in the I/R group, 22.88±3.52 cells in DMSO group, 15.00±2.07 cells in the pretreatment group, 16.75±2.60 cells in the posttreatment group, and 10.38±1.69 cells in the pre and posttreament group.The number of apoptosic cells was 1.88±0.25 in the sham group, 41.38±3.85 in the I/R group, 38.13±5.69 in the DMSO group, 22.88±2.70 in the pretreatment group, 25.63±2.93 in the posttreatment group, and 20.88±2.30 in the pre + posttreament group.The difference among drug management groups (pretreament, posttreament, and pre +posttreament) and control groups(I/R, DMSO) was significant (P <0.05).CONCLUSION: PROG may protect the ischemia brain on reperfusion injury.Reducing the expression of p53 protein and apoptosis would be one of the molecular mechanism.

Key words: progesterone, ischemia, reperfusion injury, apoptosis, p53

中图分类号:

R977.12
R965

卢娜, 李超, 李东亮. 黄体酮防治大鼠缺血再灌注脑损伤中细胞凋亡及p53蛋白的变化[J]. 中国临床药理学与治疗学, 2005, 10(9): 1041-1045.

LU Na, LI Chao, LI Dong-liang. Effects of progesterone on apoptosis and expression of p53 protein in rats during focal cerebral ischemia/reperfusion injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 1041-1045.

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