川芎素调节脑组织ET/CGRP改善大鼠局灶性脑缺血再灌注损伤  

Protective Effects of Sodium Ferulate on Focal Brain Ischemia/Reperfusion Injury by Regulating ET/CGRP of Brain Tissue in Rats

作　　者：刘萍[1] 王菊英[1] 刘文谦[2] 张晓侠[3] 李肖岩[3] 杨贵忠[1] 刘兆平[4] 张岫美[1] 

机构地区：[1]山东大学医学院药理学研究所,济南250012 [2]山东大学生命科学院,济南250100 [3]山东省精神卫生中心,济南250014 [4]山东大学新药评价中心,济南250012

出　　处：《中国药学杂志》2007年第24期1859-1863,共5页Chinese Pharmaceutical Journal

摘　　要：目的研究川芎素对大鼠局灶性脑缺血再灌注损伤的保护作用及其与内皮素(ET)、降钙素基因相关肽(CGRP)的关系。方法线栓法制备大鼠局灶性脑缺血再灌注损伤模型。Wistar大鼠随机分为假手术组、脑缺血再灌注损伤组、川芎素组(50,100和200 mg.kg-1)以及尼莫地平0.4 mg.kg-1组。脑缺血1 h再灌注24 h后,观察川芎素对大鼠神经功能缺损症状、脑梗死体积、脑组织病理形态学改变以及脑组织ET、CGRP含量的影响。结果川芎素可明显改善脑缺血再灌注损伤所致的大鼠神经功能缺损症状,缩小脑梗死体积,抑制ET的过量产生,提高脑组织CGRP含量,剂量依赖性地降低缺血脑组织中已经升高的ET/CGRP值。结论川芎素对大鼠局灶性脑缺血再灌注损伤具有明显保护作用,其作用机制可能与川芎素降低缺血脑组织中ET含量,提高CGRP含量,使缺血脑组织中失衡的CGRP/ET比值趋于正常有关。OBJECTIVE To investigate the protective effects and mechanism of sodium ferulate on focal cerebral ischemia/reperfusion injury in rats.METHODS The models of focal brain ischemia/reperfusion injury was prepared by middle cerebral artery occlusion（MCAO）in Wistar rats.One hundred and eight male Wistar rats were randomly divided into six groups：sham group,ischemia/reperfusion injury group,nimodipine group and three sodium ferulate groups,sodium ferulate was administered in the doses of 25,50,100 mg·kg^-1,respectively.One hour after ischemia and twenty-four hours after reperfusion,the extent of neurological deficits was evaluated by the method of Longa,the infarction volumes were showed with 2,3,5-triphenyltetrazoliumchloride（TTC） staining and evaluated by image analysis system.The pathological changes were determined by HE staining,and then the levels of ET and CGRP in brain tissue were measured by radioimmunoassay.RESULTS Sodium ferulate significantly ameliorated the neurological deficit and diminished the infarction volume induced by MCAO.And at the same time,sodium ferulate reduced the levels of ET and the ratio of ET/CGRP dose-dependently.CONCLUSION Sodium ferulate can protect the brain from ischemia/reperfusion injury in rats.And the neuroprotective mechanism may be related to down-regulating the levels of ET and ratio of ET/CGRP.

关 键 词：川芎素 脑缺血 再灌注损伤 内皮素 降钙素基因相关肽 

分 类 号：R965[医药卫生—药理学] R282.71[医药卫生—药学]