利多卡因和维拉帕米预处理对鼠脑缺血再灌注损伤的保护作用

A Comparitive Study on the Protective Effects of Lidocaine and Verapamil Pretreatment to Cerebral Ischemia-reperfusion Caused Injury in Gerbils

目的:比较利多卡因和维拉帕米预处理对沙土鼠脑缺血再灌注损伤的保护作用。方法:沙土鼠分为对照组、缺血再灌注组及药物预处理后缺血再灌注组,后者又分为利多卡因48 h,24 h,12 h预处理组,维拉帕米48 h,24 h,12 h预处理组。对照组及缺血组各6只,其余为每组7只。行缺血预处理后取大脑皮层组织匀浆作超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱苷肽过氧化物酶(GSH-Px)及内皮素(ET)、降钙素基因相关肽(CGRP)指标检测,每组随机选1例作电镜观察。结果:利多卡因和维拉帕米预处理各组的GSH-Px活性显著高于缺血组(P<0.05或P<0.01),两者48 h组SOD活性显著高于缺血组(P<0.05),而ET含量显著低于缺血组(P<0.05或P<0.01);利多卡因和维拉帕米预处理组在同一时间点各指标均没有差异(均P>0.05);电镜下两预处理组细胞损害比缺血组轻。结论:利多卡因和维拉帕米预处理能不同程度地减轻沙土鼠脑缺血再灌注对脑组织的损害,但2种药物间的保护作用未见明显差异。2种药物对鼠脑缺血再灌注损伤保护作用可能与增强氧自由基清除剂的活性以及减少ET的含量从而减轻ET对脑的损伤作用有关。

Objective： To study and compare the protective effects of lidocaine and verapamil pretreatment to cerebral ischemia-reperfusion caused injury in gerbils. Methods： 54 Mongolian gerbils were randomly divided into eight groups ： control group （ CG, n = 6）, ischemia group （ IG, n = 6）, lidocaine and verapamil pretreatment groups with different pretreatment times（48h, 24h, 12h, named L48, L24, L12, V48, V24, and V12, 7 mice in each group）. The cerebral cortex was removed to measure the activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA）, calcitonin gene-related peptide （CGRP）, and endothelins （ET）. One gerbil from each group was randomly selected for the observation of the ultrastructural changes of cerebral tissue with electronic microscope. Results： In all of lidocaine and verapamil pre-treated groups, the activities of GSH-Px were significantly higher than those in IG（ P 〈 0.05 or P 〈 0.01 ） ; In 48 h groups, the SOD activities were significantly higher, and the ET contents were significantly lower than those in IG （P 〈0.05 or P 〈0. 01, and P 〈0. 05 or P 〈0.01 ） ; However, there was no difference between lidocaine and verapamil prtreated groups at each time point in regard of the activities of SOD, GSH-Px, and the contents of ET, and MDA. Compared to the lidocaine and verapamil pretreatment groups, the ultrastructure of cerebral tissue was more seriously damaged in IG. Conclusions： Lidocaine and verapamil pretreatment before cerebral ischemia-reperfusion can protect the cerebral tissue from ischemia-reperfusion injury, and no difference exists between the protective effects of lidocaine and verapamil. The mechanism was related with the increase of GSH-Px and SOD activities as well as the decrease of ET and CGRP levels.