硝苯地平预处理对大鼠脑缺血再灌注损伤的影响

Effect of Nifedipine on Cerebral Ischemia Reperfusion Injury in Rats

目的:探讨硝苯地平对脑缺血/再灌注(I/R)大鼠大脑的保护作用。方法:将30只雄性Wistar大鼠随机分为假手术(sham)组、I/R组和硝苯地平+I/R组,每组10只大鼠。I/R组大鼠阻断左颈总动脉1 h,再灌注24 h;硝苯地平+I/R组于手术前2 h通过导管口服给药硝苯地平(10μg·kg^(-1)),手术方法同I/R组。根据2,3,5-氯化三苯基四氮唑(TTC)染色法计算各组大鼠脑梗死体积,通过苏木精-伊红(HE)染色观察各组大鼠缺血脑组织病理学改变,通过ELISA分析各组大鼠脑组织丙二醛(MDA)、总谷胱甘肽(tGSH)、环氧化酶1(COX-1)、环氧化酶2(COX-2)和超氧化物歧化酶(SOD)含量。结果:与Sham组梗死体积(0)相比,IR组大鼠梗死体积[(35.3±4.1)%]增加(P<0.05);与IR组相比,硝苯地平组大鼠梗死体积[(23.6±3.0)%]降低(P<0.05);与Sham组相比,I/R组大鼠MDA[(15.0±1.6)nmol·mg^(-1)]和COX-2水平[(27.4±2.9)μ·mg^(-1)]增高,COX-1[(3.1±0.4)μ·mg^(-1)]、tGSH[(2.1±0.2)nmol·mg^(-1)]和SOD水平[(21.0±2.3)μ·mg^(-1))]降低,差异均有统计学意义(P<0.05);与I/R组相比,硝苯地平组大鼠MDA[(5.7±0.6)nmol·mg^(-1)]和COX-2水平[(5.0±0.6)μ·mg^(-1)]降低,COX-1[(9.7±0.9)μ·mg^(-1)]、tGSH[(5.6±0.6)nmol·mg^(-1)]和SOD水平[(42.3±4.6)μ·mg^(-1)]增高,差异均有统计学意义(P<0.05)。结论:硝苯地平对脑I/R损伤具有神经保护作用;这种作用可能与提高脑组织抗氧化能力,抑制炎症细胞因子过度分泌有关。

Objective:To investigate the protective effect of nifedipine on cerebral ischemia/reperfusion(I/R)in rats.Methods:Thirty male Wistar rats were randomly divided into three groups:Sham group,I/R group,and nifedipine+I/R group,with 10 rats in each group.In the I/R group,the left common carotid artery was occluded for 1 hour to induce transient cerebral ischemia and reperfused for 24 hours;Nifedipine+I/R group was given nifedipine orally through a catheter(10μg·kg^(-1)).Then the infarct volume of rats in each group were calculated according to 2,3,5-Triphenyltetrazolium chloride(TTC)staining,the histopathology characteristics of rats in each group were observed by hematoxylin-eosin(HE)staining,and the contents of Malondialdehyde(MDA),total glutathione(tGSH),cyclooxygenase-1(COX-1),cyclooxygenase-2(COX-2)and superoxide dismutase(SOD)in brain tissue of rats in each group were analyzed by ELISA.Results:Compared with the Sham group,the infarct volume of the IR group increased(P<0.05);Compared with the IR group,the infarction volume of rats in the nifedipine group decreased(P<0.05).Compared with the Sham group,the levels of MDA and COX-2 in the I/R group increased,while the levels of COX-1,tGSH,and SOD decreased(all P<0.05);Compared with the I/R group,the levels of MDA and COX-2 in the nifedipine group decreased,and the levels of COX-1,tGSH,and SOD increased(all P<0.05).Conclusion:Nifedipine has a protective effect on cerebral I/R injury.This effect may be related to improving the antioxidant capacity of brain tissue and inhibiting the excessive secretion of inflammatory cytokines.