加兰他敏中枢激活胆碱能抗炎通路对失血性休克大鼠的保护作用  

Protective Effect of Galantamine Against Hemorrhagic Shock in Rats Through Activating Brain Cholinergic Anti-Inflammatory Pathway

作　　者：黄丽丽[1] 李建国[1] 周青[1] 李光[1] 梁辉[1] 李倩[1] 

机构地区：[1]武汉大学中南医院ICU,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2010年第5期600-603,F0002,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:30671586)

摘　　要：目的:探讨中枢胆碱酯酶抑制剂加兰他敏对失血性休克大鼠的保护作用及其作用机制。方法:采用股动脉间断放血法制备失血性休克动物的模型。60只成年SD大鼠随机分为假休克(假Hem)组、休克(Hem)组、加兰他敏(Gal)组,迷走神经切断(Vgx)组、硫酸阿托品(AS)组、α-银环蛇毒素(α-BGT)组,每组10只。各组动物均行右侧股动脉置管并连续监测平均动脉压(MAP),模型稳定后20min取动脉血标本,进行血浆肿瘤坏死因子-α(TNF-α)、血气及乳酸值检测;处死动物取肺脏和肝脏标本行病理学观察。另取40只大鼠随机分成假休克、休克、加兰他敏和迷走神经切断4组,仅观察生存状况而不作其他干预,观察时间为180min。结果:与假Hem组比较,Hem组平均生存时间显著缩短,各时间点的生存率均显著降低(均为P<0.05),MAP值持续低下,血浆TNF-α浓度显著升高,并有严重代谢性酸中毒和高乳酸血症,同时肺脏和肝脏明显炎性病理学改变;与Hem组比较,Gal组平均生存时间延长,各时间点生存率均显著提高(均为P<0.05),MAP值呈升高趋势,血浆TNF-α浓度降低,代谢性酸中毒缓解,肺脏和肝脏的炎症明显改善。经迷走神经切断、硫酸阿托品及α-BGT拮抗后,加兰他敏的上述效应则完全抵消。结论:加兰他敏通过激活中枢M受体,对失血性休克大鼠发挥抗炎抗休克保护作用,该效应可能与激活胆碱能抗炎通路有关。Objective：To investigate the protective effect and mechanism of galantamine against hemorrhagic shock in rats.Methods：Sixty Sprague-Dawley rats were randomly divided into six groups：sham hemorrhagic（Sham）group,hemorrhagic shock（Hem）group,galantamine（Gal）group, vagotomy（Vgx）group,atropine sulfate（AS）group,and N receptor inhibitor（α-BGT）group.A blood pressure transducer was implanted in the right femoral artery for continuous monitoring of MAP,TNF-α level in blood,arterial blood lactic concentration,pH,and base excess（BE） were determined,and the tissues of lung and liver were harvested for histopathological analysis after modelling for 20 minutes.Another 40rats were randomly divided into four groups：Sham group,Hem group,Gal group,and Vgx group only for the observation of survival time and sur-vival rate.Results：Galantamine could significantly raise the survival time and survival rate,revert the hypotension in the period of hemorrhagic shock,greatly decrease plasma TNF-α concentration,improve the metabolic acidosis and the lung and liver tissue pathologic changes.But no such effects were found in Vgx group,AS group and α-BGT group.Conclusion：Galantamine might produce a protective effect on hemorrhagic shock in rats through activation of central M receptor,and the mechanism maybe relate to the activation of the cholinergic anti-inflammatory pathway.

关 键 词：失血性休克 迷走神经 加兰他敏 胆碱能抗炎通路 

分 类 号：R631.4[医药卫生—外科学]