银杏二萜内酯葡胺注射液对缺血性脑卒中急性期损伤的保护作用

Protection of Diterpene Ginkgolides Meglumine Injection on acute injury of ischemic stroke in rats

目的探讨银杏二萜内酯葡胺注射液(DGMI)对缺血性脑卒中的保护作用、治疗时间窗及相关机制。方法制备大鼠大脑中动脉阻塞(t MCAO)模型,缺血1 h后ip不同剂量的DGMI(1.25、2.50、5.00、10.00 mg/kg),缺血1.5 h后血流复灌,再灌注24和72 h评价大鼠神经运动功能,72 h时测定脑梗死体积、脑组织含水量以及氧化应激和IL-1β水平;选取DGMI有效剂量5.0 mg/kg,分别于再灌注前0.5 h、再灌后1、2、3和6 h时给药,3 d后取材研究药物治疗时间窗。结果2.5、5.0 mg/kg剂量的DGMI改善大鼠再灌注24 h后的神经运动功能、减小脑梗死体积、减轻脑水肿、增强缺血脑组织的超氧化物歧化酶(SOD)的活力,减弱肌酸激酶(CK)、乳酸脱氢酶(LDH)的活力,降低丙二醛(MDA)、IL-1β水平。DGMI5.0 mg/kg在t MCAO大鼠再灌注3 h内给药均改善神经运动功能障碍、减小脑梗死体积、减轻脑水肿。结论 DGMI对大鼠缺血性脑卒中急性期损伤具有保护作用,治疗时间窗少于缺血再灌注后6 h,其机制与抗氧化应激、抑制炎症相关。

Objective To investigate the protective effect and therapeutic window of DGMI on ischemic stroke in rats,and to explore the related mechanism.Method The rats were subjected to middle cerebral artery occlusion （MCAO） for 90 min followed by 72 h of reperfusion.DGMI （i.p.,1.25,2.5,5.0,and 10.0 mg/kg,Bid） was administered at 1 h after the onset of ischemia.Neurological score was evaluated after 24 and 72 h of reperfusion rcspectively.In fact volume,cerebral water content,oxidative stress markers,and IL-1β were evaluated after 72 h of reperfusion.The rats were treated with DGMI 5.0 mg/kg 0.5 h before reperfusion or 1 h,2 h,3 h,and 6 h after reperfusion to determined therapeutic window.Result Treatment with DGMI （2.5,5.0 mg/kg） significantly ameliorated neurological deficit,infarct volume and cerebral water content after cerebral ischemia reperfusion.DGMI also reduced the content of malonaldehyde （MDA）,IL-1β,down-regulated the activities of creatine kinase （CK）,lacticdehydrogenase （LDH）,and up-regulated the activities of superoxide dISmutase （SOD）.Treatment with DGMI 5.0 mg/kg exhibited protective effects when administered at all time points except for 6 h after reperfusion.Conclusion DGMI plays a certain protective role in ischemic stroke of rats,and the effect may be related to the improvement on the antioxidant capacity of brain tissue and the inhibition of overproduction of inflammatory cytokine.Moreover,the therapeutic window of DGMI isless than 6 h after reperfusion.