阿司匹林对大鼠脑缺血再灌注损伤细胞凋亡的影响

Effects of aspirin on cell apoptosis in focal cerebral ischemia-reperfusion injury rats

目的 观察阿司匹林对大鼠脑缺血 再灌损伤时的抗凋亡作用。方法 线栓法制作局部脑缺血 2h、再灌 2 4h模型 ,观察阿司匹林 6mg·kg-1和 6 0mg·kg-1对正常神经元密度、凋亡细胞数目及bcl 2和bax基因蛋白的影响。TUNEL法检测细胞凋亡 ,免疫组化法检测bcl 2和bax基因蛋白。相邻组织切片HE染色 ,计数正常神经元密度。结果 两个剂量阿司匹林均明显抑制再灌引起的正常神经元的丢失和凋亡细胞数目 ,提高bcl 2 /bax。 6mg·kg-1组主要提高bcl 2的表达 ;6 0mg·kg-1组除提高bcl 2表达外 ,对bax表达的抑制更明显。两个剂量对bcl 2和bax的影响均有组间差异 ,但对bcl 2 /bax的影响却无组间差异。结论 阿司匹林可明显减轻脑缺血 再灌引起的脑损伤 ,有明显的抗凋亡作用 ,其机制可能与提高bcl 2 /bax有关。

AIM To investigate the effects of aspirin on apoptosis in focal cerebral ischemia-reperfusion rats. METHODS Right middle cerebral artery was occluded by inserting a thread through internal carotid artery for 2 h, and then reperfused for 24 h. Different doses of aspirin were ig administrated at reperfusion 0 h and 6 h. The neuronal density, and the numbers of apoptotic[FQ(15。46,X-WZ]-cells from occluded brain were estimated. The ratio of bcl-2 protein and bax protein in brain tissue from the occluded side were assayed. Apoptosis was measured in paraffin sections with TUNEL method. Immunohistochemical staining method was used for bcl-2 and bax detection. Adjacent sections were stained with hematoxylin and eosin, and neuronal density in injured regions subfield was counted. RESULTS Most of neurons in the injured regions survived ischemia-reperfusion result when 6 mg·kg -1 and 60 mg·kg -1 doses of aspirin were given, whereas most of vehicle group neurons were lost without aspirin treatment. The significant difference among the groups was discovered. The numbers of apoptotic cells were dramatically reduced by 6 mg·kg -1 and 60 mg·kg -1 doses of aspirin. The ratio of bcl-2 and bax was increased by aspirin. No significant difference between 6 mg·kg -1 and 60 mg·kg -1 groups was discovered. CONCLUSION Aspirin reduced the neuronal damage and inhibited apoptosis induced by ischemia-reperfusion. The anti-apoptosis effects of it might be attributed to its effects by increasing the ratio of bcl-2 and bax.-