清热化淤方对脑缺血预处理大鼠ATF4、Caspase-12表达的影响

目的 观察清热化淤方对脑缺血预处理大鼠缺血再灌注后ATF4、Caspase-12 mRNA及其蛋白表达的影响.方法 SD大鼠160只,随机分为假手术组(SO)、脑缺血再灌注组(MCAO)、脑缺血预处理组(BIP)、清热化淤方干预组(QRHY)四组,每组按照再缺血后12h、1d、2d、3d四个时间点分为4个亚组.采用二次线栓法制备大鼠局灶性脑缺血预处理模型,用原位杂交法和Western blot法观察再缺血后各个时间点ATF4、Caspase-12 mRNA及其蛋白的表达变化.结果 ①MCAO组12h ATF4mRNA及其蛋白表达均达高峰(P＜0.01),随再灌注时间延长其表达逐渐下降;BIP组较MCAO组ATF4mRNA及其蛋白表达均明显降低(P＜0.05,P＜0.01);QRHY组较BIP组进一步降低其表达(P ＜0.05,P＜0.01).②MCAO组12 h Caspase-12 mRNA及其蛋白表达均达高峰,随再灌注时间延长其表达逐渐下降(P ＜0.01);BIP组较MCAO组Caspase-12mRNA及其蛋白表达均明显降低(P＜0.05,P＜0.01);QRHY组较BIP组进一步降低其表达(P＜0.05,P＜0.01).结论 清热化淤方可通过下调大鼠脑缺血预处理后ATF4、Caspase-12表达发挥其神经保护作用.

Effect of Qingre Huayu Prescription on the Expression of Activating Transcription Factor 4 and Caspase-12 after Cerebral Ischemic Preconditioning in Rats

Objective To investigate the effect of cerebral ischemic preconditioning(IPC) on the expression of activating transcription factor 4(ATF4) and Caspase-12 mRNA and protein after focal cerebral ischemia/reperfusion(I/R) in rats.Methods 160 male SD rats were randomly divided into four groups:sham-operation group,middle cerebral artery occlusion(MCAO) group,brain ischemia preconditioning(BIP) group and QRHY group.Each group was further divided into 4 subgroups according to 12h,1d,2d and 3d after I/R.The BIP models were made in order to measure the expression of ATF4 and Caspase-12 mRNA and protein by in situ hybridization and Western blot.Results The expression of ATF4 and cacpase-12 was mRNA and its protein all increased and reached the peak at 12h(P<0.01),then was decreased continuously 1 d later.Compared with MCAO group,IPC could decrease its expression(P<0.05,P<0.01).QRHYP treatment could further reduce its expression as compared to BIP group(P<0.05).Conclusion QRHYP can protect neurons through inhibiting the expression of ATF4 and caspase-12 after IPC in rats.