Ding Ning, Wang Fang, Xiao Hui, Wang Di-fen
Department of Pathophysiology and Key Laboratory of Functional Proteomics of Guangdong Province, Southern Medical University, Guangzhou 510515, and Department of Anesthesiology, Affiliated Hospital of Guangzhou Medical College, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2007 Jul;27(7):1061-4.
To observe the protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils.
Thirty-three Mongolian gerbils were randomized into the control group (group A, n=6, with sham operation), ischemia group (group B), and 3 verapamil groups (groups C, D, and E, n=7) with intraperitpneal verapamil injection (2 mg/kg) 48, 24 and 12 h before ischemia, respectively. In group A, the bilateral common carotid arteries were only exposed without clamping, and in the other 4 groups, the arteries were clamped for 20 min followed by reperfusion for 50 min. The gerbils were then decapitated and the forebrain cerebral cortex was removed to determine superoxide dismutase (SOD) and glutathione (GSH) activities and measure the contents of malondial dehyde (MDA), endothelin (ET) and calcitonin gene-related peptide (CGRP). The left forebrain cerebral cortex was sampled in each group to observe the ultrastructural changes under electron microscope.
In groups C and D, SOD activities were significantly higher than those in group B (P<0.05), and in group E, the SOD activity elevation was not statistically significant (P>0.05). In groups C, D and E, GSH activity was significantly higher than that in group B (P<0.05). MDA content was significantly lower in groups C and D than in group B (P<0.05), but comparable between groups E and B (P>0.05). ET content was also significantly lower in the pretreatment groups (P<0.05), but CGRP content higher (not statistically so, however) than those in group B. The more serious ultrastructural damage of the cerebral tissue was observed in group B, but only mild damage was found in the verapamil groups.
Verapamil given 12-48 h before cerebral ischemia may protect the gerbils from cerebral ischemia-reperfusion injury by enhancing SOD, GSH activities and decreasing ET content.
观察维拉帕米预处理对沙土鼠脑缺血再灌注损伤的保护作用。
将33只蒙古沙土鼠随机分为对照组(A组,n = 6,行假手术)、缺血组(B组)和3个维拉帕米组(C组、D组和E组,n = 7),分别在缺血前48、24和12小时腹腔注射维拉帕米(2 mg/kg)。A组仅暴露双侧颈总动脉但不夹闭,其他4组夹闭动脉20分钟,随后再灌注50分钟。然后将沙土鼠断头,取出前脑皮质,测定超氧化物歧化酶(SOD)和谷胱甘肽(GSH)活性,测量丙二醛(MDA)、内皮素(ET)和降钙素基因相关肽(CGRP)的含量。每组取左侧前脑皮质,在电子显微镜下观察超微结构变化。
C组和D组的SOD活性显著高于B组(P < 0.05),E组SOD活性升高无统计学意义(P > 0.05)。C组、D组和E组的GSH活性显著高于B组(P < 0.05)。C组和D组的MDA含量显著低于B组(P < 0.05),但E组和B组相当(P > 0.05)。预处理组的ET含量也显著降低(P < 0.05),但CGRP含量高于B组(然而无统计学意义)。B组脑组织超微结构损伤更严重,而维拉帕米组仅发现轻度损伤。
脑缺血前12 - 48小时给予维拉帕米可通过增强SOD、GSH活性和降低ET含量保护沙土鼠免受脑缺血再灌注损伤。