脑缺血缺氧后X-连锁凋亡抑制蛋白的表达及黄体酮的干预研究

The expression of XIAP in cerebral ischemia and research of progesterone intervention

目的观察脑梗死大鼠脑缺血半暗带脑组织内x-连锁凋亡抑制蛋白的表达情况，并观察黄体酮治疗对其表达水平及神经细胞凋亡的影响，以进一步探讨黄体酮神经保护作用的机制。方法选择成年雄性S-D大鼠102只，质量为260～310g，随机分为假手术组、模型组、溶剂治疗组、黄体酮治疗组。分别于脑梗死12h、24h、48h3个时间点处死大鼠，取出脑组织，应用免疫组化染色、Westernblot技术检测各组大鼠缺血半暗带内X-连锁凋亡抑制蛋白的表达情况；应用原位末端标记法检测脑组织细胞的凋亡情况。采用单因素方差分析对上述结果进行统计学分析，取α／=0．05为检验水准。结果脑梗死发生后，缺血半暗带内X-连锁凋亡抑制蛋白的表达水平较假手术组有所增高，经黄体酮治疗后，其表达水平明显升高，与模型组、溶剂治疗组比较，差异有统计学意义（P〈0．05），黄体酮治疗组凋亡细胞数明显减少，与模型组、溶剂治疗组比较，差异亦有统计学意义（P〈0．05）。结论黄体酮可减少脑梗死大鼠缺血半暗带内的脑细胞凋亡，提高脑组织中X-连锁凋亡抑制蛋白表达可能是其发挥保护作用的分子机制之一。

Objective This study was designed to investigate the expression of XIAP in ischemia penumbra of cere- bral infarction rats and research about the influence of progesterone on expression of XIAP and apoptosis in cerebral ische- mia in rats. Methods All S-D rats, weighted 260 g- 310 g, were randomly divided into four groups：sham-operated （con- trol） group,ischemic group, vehicle-treated group and PROG-treated group. Immunohistochemistry and western Western blot techniques were applied to detect the expression of XIAP at 12 h,24 h and 48 h after permanent middle cerebral artery oc- clusion（pMCAO） ,TdT-mediated dUTP nick end labeling（TUNEL） was used to investigate apoptosis cell in the brain tis- sues. One-way ANOVA was used to check any changes in XIAP and brain cell apoptosis after pMCAO. Results The ex- pression of XIAP were was significantly increased in isehemia penumbra after cerebral infarction in comparison with vehicle- treated groups （ P 〈 0.05 ） , following PROG treatment, the expression of XIAP were was significantly increased in comparison with ischemic groups and vehicle-treated groups （P 〈 0.05 ）. In addition, PROG also significantly reduced apoptosis cells of injured brain when compared with ischemic groups and vehicle-treated groups （ P 〈 0.05 ）. Conclusion PROG significantly decreases the cells apoptosis in ischemia penumbra brain,increasing the expression of XIAP may be one of the molecule mechanisms of the neuroprotective effects of PROG in injured brain.