曲古抑菌素A预处理对小鼠脑缺血再灌注损伤皮质炎症反应和凋亡的影响*

Effect of Trichostatin A on cerebral cortex inflammation and apoptosis in mouse model of cerebral ischemia reperfusion injury

摘要:

目的 探讨曲古抑菌素A预处理在小鼠脑缺血再灌注损伤中对大脑皮质炎症反应和凋亡的影响。方法 Balb/c小鼠随机分为3组：假手术组（S组）、缺血再灌注组（IR组）、曲古抑菌素A预处理组（预处理组），每组10只。采用颈部切口大脑中动脉线栓（MCAO）法缺血1?h，再灌注24?h复制脑缺血再灌注模型，预处理组在复制脑缺血再灌注模型前连续3?d腹腔注射曲古抑菌素A 5?mg/kg。取脑皮质组织，光学显微镜下观察病理学结果，ELISA检测TNF-α、IL-1β，免疫组织化学法检测Bcl-2、Bax、Caspase-3，TUNEL检测细胞凋亡。结果 3组TNF-α、IL-1β、Bax、Bcl-2及Caspase-3比较，差异有统计学意义（P?<0.05）。与S组比较，IR组病理学损伤严重，TNF-α、IL-1β、Bax、Caspase-3阳性表达水平升高，Bcl-2降低（P?<0.05）；与IR组比较，预处理组病理学损伤减轻，TNF-α、IL-1β、Bax、Caspase-3阳性表达水平降低，Bcl-2升高（P?<0.05）。结论 曲古抑菌素A预处理能抑制炎症因子、凋亡因子的表达及减少细胞凋亡，从而减轻脑缺血再灌注损伤。

关键词:再灌注损伤;模型，动物;曲古抑菌素A;因子，炎症;凋亡诱导因子

Abstract:

Objective To evaluate effect of Trichostatin A (TSA) on inflammatory factors and apoptosis in mouse model of cerebral ischemia reperfusion injury. Methods Mice were randomly divided into three groups (n?=?10): sham (S) group in which mouse received all surgical procedure except ligation of arteries, ischemia/reperfusion (IR) group in which mouse received ligation of middle cerebral artery for one hour following by blood reperfusion for 24 hours, TSA group in which mouse were pretreated with TSA (5?mg/kg) for 3 days before ischemia/reperfusion insult. Histopathology was detected by HE-staining; circulating concentration of TNF-α, IL-1β were measured by ELISA; expression of Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry; and apoptosis rate was identified by TUNEL. Results Brain tissue in IR group exerted obvious histological deterioration and expression of TNF-α, IL-1β; Bax and Caspase-3 were increased significantly when compared with those in S group (P?

Key words:reperfusion injury; model; animal; Trichostatin A; factor; inflammation; apoptosis inducing factor