目的 观察脑缺血预处理(CIP)对大鼠大脑皮质晚期糖基化终末产物受体(RAGE)和Toll样受体4(TLR4)的表达变化.方法 将108只SPF级SD健康雄性大鼠随机分为CIP组、缺血再灌注(I/R)组和假手术纽(Sham 组),每组36只;大鼠建立大脑中动脉栓塞模型后,每组随机选6只于再灌注1d时处死,采用TTC法检测脑梗死体积,之后于再灌注后12h,1、2、3和7d共5个时间点处死大鼠,每个时间点6只,通过RT-PCR法测定RAGE和TLR4 mRNA表达.结果 CIP组大鼠在12h、1、2、3和7d的神经功能行为缺损评分较I/R组明显减低(P＜0.05,P＜0.01).CIP组1d脑梗死体积明显低于I/R组[(19.04±1.65)％ vs (34.55±4.78)％,P＜0.05].CIP、组和I/R组RAGE、TLR4 mRNA表达均显著高于Sham组(P＜0.05),均于1d时达高峰,随再灌注时间延长,两者表达逐渐下降,CIP组较I/R组表达均明显降低(P＜0.05).结论 CIP可使大脑产生缺血耐受,其机制可能与下调I/R损伤时RAGE和TLR4的表达有关.%Objective To study the effect of cerebral ischemia preconditioning (CIP) on expression of receptor for advanced glycation end (RAGE) products and Toll-like receptor 4 (TLR4) in rat cerebral cortex.Methods One hundred and eight SPF healthy male SD rats were randomly divided into CIP group (n=36),I/R group (n=36),and sham operation group (n=36).After a middle cerebral artery occlusion model of rats was established,6 rats randomly selected from each group were killed on day 1 after reperfusion.The infarction size was measured with TTC staining.The rats were then sacrificed at 12 h and on days 1,2,3 and 7 after reperfusion.Expressions of RAGE products and TLR4 mRNA were detected by RT-PCR.Results The average neural behavioral score was significantly lower in CIP group than in I/R group at 12 h and on days 1,2,3 and 7 after reperfusion (P＜0.05,P＜0.01).The infarction size was significantly smaller in CIP group than in I/R group on day 1 after reperfusion (19.04％±1.65％ vs 34.55 ％ ±4.78％,P＜0.05).The expression levels of RAGE products and TLR4 mRNA were significantly higher in CIP group and I/R group than in sham operation group (P＜0.05) and reached their peak on day 1 after reperfusion and then gradually decreased with the prolonged time of reperfusion.The expression levels of RAGE products and TLR4 mRNA were significantly lower in CIP group than in I/R group (P＜0.05).Conclusion CIP increases the tolerance to cerebral ischemia by downregulating the expression of RAGE products and TLR4 mRNA in rats following I/R injury.
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