胆碱能M受体信号通路在芍药苷抗脑缺血神经保护中的作用

摘要

目的 研究芍药苷(PAE)调节胆碱能M受体及其信号通路抗脑缺血的神经保护作用,为脑缺血临床防治提供理论与实验依据.方法在大脑中动脉梗死(MCAO,缺血90 min,再灌24 h)诱导的大鼠局灶性脑缺血模型上,观察缺血同时给予PAE(2.5、5和10 mg·kg-1,ip,14 days)对脑梗死体积及神经症状的影响;于再灌24 h后,分别取皮层、海马和纹状体脑组织,以RT-PCR方法研究PAE对M受体、G蛋白及ATP敏感性钾通道基因表达的影响.结果 PAE可明显降低脑梗塞体积、改善神经功能缺陷;拮抗脑缺血诱导的M1、M3、M4和M5基因表达的降低及M2基因表达的增高;抑制Gi蛋白的病理性增高及Gαq/11蛋白的降低;逆转Kir6.2/Kir6.1的病理性降低.结论 M受体及其通路可能参与PAE的抗脑缺血神经保护作用.%Aim To examine neuroprotection induced by PAE and its molecular mechanisms. Methods In rat middle cerebral artery occlusion ( MCAO ) and reperfusion model, PAE( 2. 5, 5. 0,10 mg ? Kg"1, I. P. , 14 days ) significantly reduced the infarct volume and reversed neurological deficits caused by ischemia. Further investigation was carried out through examining the effects of PAE on muscarinic receptor signaling pathways including muscarinic receptors, G proteins and ATP-sensitive potassium channel ( KATP ). Results PAE markedly increase the Mj-type muscarinic re-ceptor related signaling activation, however, it inhibited M2-type muscarinic receptor related signaling activation. Second, PAE increased Kir6. 2/Kir6. 1 ratio by activating KATP channels. The above effects of PAE all contributed to its neuroprotection. Conclusion Neuroprotection induced by PAE is targeting muscarinic receptor signaling pathways.