盐酸戊乙奎醚对大鼠急性全脑缺血再灌注损伤的影响  

Effect of penehyclidine hydrochloride in acute global cerebral ischemia-reperfusion injury rats

作　　者：庞涛[1] 许铁[1] 纵雪梅[1] 梁高永[1] 燕宪亮[1] 

机构地区：[1]徐州医学院附属医院急救中心,徐州221002

出　　处：《中国临床药学杂志》2007年第6期352-356,共5页Chinese Journal of Clinical Pharmacy

基　　金：江苏省高校自然科学计划(编号:04KJD320206)资助项目

摘　　要：目的探讨胆碱受体阻滞剂盐酸戊乙奎醚对三动脉阻断法全脑缺血再灌注损伤模型大鼠的脑保护作用。方法♂性SD大鼠随机分为假手术组、NS组、东莨菪碱组和盐酸戊乙奎醚组,后3组大鼠缺血前40min分别腹腔注射NS(1mL)、东莨菪碱(0.01mg·kg^(-1))和盐酸戊乙奎醚(0.01mg·kg^(-1))。分别于脑缺血再灌注2、12、24h、3和7d取材测定海马CAl区存活神经元数量、凋亡神经元数量、bel-2和bax阳性神经元数量。另取部分动物于缺血再灌注4d用TIC法测定脑梗死体积。结果与NS组比较,盐酸戊乙奎醚组和东莨菪碱组均可见CA1区存活神经元数目增加,凋亡神经元数目减少,海马CAl区bel-2提前并延长表达,脑梗死体积缩小。盐酸戊乙奎醚组bax表达下降。盐酸戊乙奎醚组较同等剂量的东莨菪碱组改善更明显。结论盐酸戊乙奎醚可能通过改变bel-2/bax的比例对脑缺血再灌注损伤大鼠产生脑保护作用。AIM To investigate the effect of a muscarinic receptor antagonist （penehyclidine hydrochloride）in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats.METHODS One hundred and fortyfourty SD rats were randomly divided into 4 groups：sham operated group,vehicle treated group （saline 1 mL,ip）, scopolamine treated group （0.01 mg·kg^-1,ip）and penehyclidine hydrochloride treated group （0.01 mg·kg^-1,ip） with drugs injected 40 min before ischemia respectively.The ischemic duration was 10 min.HE staining,TUNEL staining and immunohistochemical reactions of bax and bcl-2 were carried out at the time points of 2,12,24 h,3 and 7 d after reperfusion.Some animals were subjected to TIC staining for assessment of infarction volume on the d 4 after reperfusion.RESULTS As compared with the vehicle treated group,both penehyclidine hydrochloride treatment and scopolamine treatment increased the survival pyramidal cells （P〈0.05 or P〈0.01）,decreased the numbers of apoptotic neurons （P〈0.05 or P〈0.01）,accelerated and extended the expression of bcl-2 （P〈0.01）in the CA1 subfield of hippocampus.Both of the drug treatments attenuated the cerebral infarction volume （P〈0.05 or P〈0.01）.Penehyclidine hydroehloride treatment lowered the expression of bax （P〈0.05 or P〈0.01）.There was more significant improvement in penehyelidine hydroehloride treated group than in scopolamine treated group in the same doses （P〈0.05）. CONCLUSION Penehyelidine hydroehloride may provide neuroproteetion in acute global cerebral isehemia-reperfusion injury rats by altering the bel-2/bax ratio.

关 键 词：盐酸戊乙奎醚 脑缺血/再灌注损伤 细胞凋亡 大鼠 

分 类 号：R96[医药卫生—药理学]