阿司匹林预处理对大鼠局灶性脑缺血再灌注后神经细胞凋亡和Bcl-2、Bax蛋白表达的影响

目的观察预先使用阿司匹林(ASA)进行药物处理对大鼠局灶性脑缺血/再灌注(CI/RP)损伤后神经细胞凋亡及其调节基因(Bcl-2、Bax)表达的影响。方法48只SD雄性大鼠被随机分为对照组(n=12)和实验组(n=36),实验组又分为:小剂量组(ASA10 mg/kg)(n=12)、中剂量组(ASA50mg/kg)(n=12)、大剂量组(ASA150mg/kg)(n=12)。实验组于术前5d连续给予相应剂量的ASA灌胃。然后建立大鼠局部脑缺血2h、再灌24h的动物模型。第6天处死各组大鼠,TTC染色法测定脑梗死体积,TUNEL技术原位标记凋亡细胞,免疫组化法检测凋亡调节基因相关蛋白Bcl-2和Bax的表达。结果ASA干预后,小、中、大剂量ASA组梗死病灶体积与对照组相比均减小,缺血周边区凋亡细胞阳性率均显著降低。小、中剂量ASA组的作用优于大剂量ASA组,小,中剂量两个实验组缺血区域Bcl-2蛋白的表达增加,Bax蛋白的表达降低,3个实验组间进行比较,小、中剂量ASA组的作用优于大剂量ASA组。结论ASA预处理可以缩小大鼠脑缺血再灌注损伤后的梗死体积,可以减少大鼠缺血再灌注损伤脑组织的细胞凋亡,这一过程可能与上调Bcl-2蛋白的表达和减少Bax蛋白的表达有关,抑制CI/RP后细胞凋亡的表达可能是ASA的神经保护作用之所在。

Effects of aspirin pharmacological preconditioning on apoptosis and expression of Bcl-2 and Bax in rats following focal cerebral ischemia and reperfusion

Objective To investigate the effects of aspirin preconditioning on apoptosis and expression of Bcl-2 and Bax in rats following focal cerebral ischemia and reperfusion.Methods 48 SD rats were randomly devided into four groups:three therapy groups with different doses of ASA(low dose:10 mg/kg,middle dose,50mg/kg and large dose,150 mg/kg)and the control group via a lavage rote right before focal cerebral ischemia.Then the rats were killed on the sixth day and some of the brains were removed to measure the infarct volume,the others were detected apoptosis by TUNEL technology and protein bcl-2,protein bax levels by immunohistochemistry technology.Results When the ASA of different doses were lavaged to the rats of the three therapy groups,the results changed as follows:the neurologic impairment lessened,the infarct volume reduced,the number of TUNEL positive cells decreased,the protein expression of bcl-2 increased as well as protein Bax expression reduced.Conclusion The effect of ASA pharmacological preconditioning can reduce infarct volume,and inhibit neuron apoptosis of ischemic area via enhanced protein Bcl-2 expression as well as reduced protein Bax expression.