异氟醚对乙酰胆碱诱导的细胞外信号调节激酶磷酸化的抑制效应  

Inhibition effect of acetylcholine-induced phosphorylation of extracellular signal-regulated kinase by isoflurane

作　　者：邢准[1] 张岩生[1] 刘坤[1] 邱鹏[1] 

机构地区：[1]中国医科大学附属盛京医院麻醉科,沈阳110004

出　　处：《实用药物与临床》2014年第5期558-561,共4页Practical Pharmacy and Clinical Remedies

摘　　要：目的研究异氟醚如何影响乙酰胆碱诱导的细胞内信号传递,探讨挥发性麻醉药影响认知功能的分子机理。方法培养的神经元样PC12细胞随机分成对照组和异氟醚组。对照组正常培养,异氟醚组用1.2%异氟醚处理2 h,分别于处理后0 min、1 h、3 h加入碘化乙酰胆碱(ACh)刺激2 min后收集细胞,采用Westem blot技术检测基础水平和乙酰胆碱诱导下细胞外信号调节激酶1/2(ERK1/2)的磷酸化水平和蛋白激酶B(PKB)的活性。结果单纯ACh刺激可导致ERK1/2磷酸化水平显著增加(P<0.01),异氟醚处理后0 min和1 h乙酰胆碱诱导的ERK1/2磷酸化水平明显降低,3 h时恢复到正常水平。与对ERK的影响效应不同,单独异氟醚处理可迅速增加基础状态下PKB的磷酸化水平(P<0.05),但1 h后即恢复正常水平。结论异氟醚可以长时程减弱乙酰胆碱诱导的ERK活化,从而干扰胞内信号传递,这可能与术后认知功能障碍发生密切相关。Objective To investigate the effect of isoflurane on acetylcholine-induced intracellular signaling,and to explore the molecular mechanism underlying cognitive deficits caused by volatile anesthetics exposure. Methods PC12 cells were exposed to 1. 2% isoflurane for 2 h. subsequently,acetylcholine iodide was applied to the cells for2 min at 0 min,1 h and 3 h separately. Western blot was used to assay basal phosphorylation and acetylcholine-induced phosphorylation of extracellular signal-regulated kinase 1 /2（ERK） 1 /2 and protein kinase B（ PKB）. Results ACh stimulation alone led to significant increase of ERK1 /2 phosphorylation levels. After isoflurane exposure,acetylcholineinduced ERK1 /2 phosphorylation was persistently reduced at 0 min and 1 h,until 3 h after exposure,acetylcholine-induced ERK1 /2 phosphorylation had returned to control levels. In contrast,immediately after isoflurane exposure,basal PKB phosphorylation significantly augmented but had returned to normal levels at 1 h after exposure. Conclusion Prolonged attenuation of acetylcholine-induced ERK activation caused by isoflurane exposure may interfere in the intracellular signal transmission and subsequently development of postoperative cognitive dysfunction.

关 键 词：异氟醚 乙酰胆碱 细胞外信号调节激酶1 2 蛋白激酶B 

分 类 号：R614[医药卫生—麻醉学]