药物干预对大鼠急性脑缺血再灌注损伤神经元的保护作用

Protection of drug intervention on neurons of rats with acute cerebral ischemia-reperfusion injury

目的探讨脑蛋白及银杏叶提取物对大鼠急性脑缺血再灌注损伤后缺血半暗带神经元的保护作用及机制。方法 600只雄性Wist-ar大鼠随机分为4组(对照组、蛋白组、银杏叶组、联合组),每组大鼠根据缺血后再灌注不同时间又分为缺血2 h再灌注6、12、24、72 h、7 d五个亚组(30只/亚组)。采用线栓法制备大鼠缺血2 h再灌注模型,除对照组外,其余三组均采用药物进行干预。分别于再灌注6、24、48、72 h及7 d断头取脑,观察缺血半暗带脑组织Na+-K+-ATP酶活性、脑组织水肿程度、脑梗死范围及神经症状评分的变化。结果对照组大鼠脑缺血半暗带神经元Na+-K+-ATP酶活性于6 h开始降低,48 h达最低值,72 h稍有回升,7 d趋于稳定。与单一用药组(蛋白组或银杏叶组)比较,联合组能显著提高大鼠缺血半暗带神经元Na+-K+-ATP酶活性(48、72 h亚组,P值均为0.000),降低脑组织含水量(24、48、72 h亚组,P值均为0.000),减小脑梗死面积(24、48、72 h、7 d亚组,P值均为0.000),减少神经症状评分(48、72 h、7 d亚组,P值均为0.000)。结论联合用药较单一用药能更有效地抑制缺血级联反应,从而最大限度地挽救缺血半暗带神经元的功能。

Objective To study the protective effect of combined therapies on cerebral ischemia/reperfusion injury in ischemic penumbra tissue. Methods 600 male Wistar rats were randomly divided into control, protein, ginkgo biloba and combination groups. The four groups were further divided into 6, 24, 48, 72 h and 7 d groups according to the time of reperfusion. The model rats of ischemia reperfusion （2 hours） were induced by thread approach. Except the control group, rats in other 3 groups received medical interventions. The rats were executed at reperfusion 6, 24, 48, 72 h, 7 d to observe the neurological symptoms, the activities of Na -K -ATPase, the changes of brain water content and infarction size. Results The activities of Na ＋ -K -ATPase were down-regulated in control group, beginning at 6 h, botto- ming at 48 h, up at 72 h and steadying at 7 d. Compared with single medication （protein group or ginkgo biloba group）, combined therapies could improve the activities of Na ＋ -K ＋ -ATPase significantly （48, 72 h, P = 0. 000 ）, reduce the brain water content （ 24, 48, 72 h, P = 0. 000）, infarction size（24, 48, 72 h,7 d, P = 0. 000） and neurological symptoms grade（48, 72 h,7 d, P = 0. 000）. Conclusions Combined therapies can effectively inhibit ischemic cascade than single medication, save neuronal function of ischemic penumbra maximally.