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[摘要]
目的 探討銀杏二萜內(nèi)酯葡胺注射液(DGMI)對缺血性腦卒中的保護作用、治療時間窗及相關(guān)機制。方法 制備大鼠大腦中動脈阻塞(tMCAO)模型,缺血1 h后ip不同劑量的DGMI(1.25、2.50、5.00、10.00 mg/kg),缺血1.5 h后血流復灌,再灌注24和72 h評價大鼠神經(jīng)運動功能,72 h時測定腦梗死體積、腦組織含水量以及氧化應(yīng)激和IL-1β水平;選取DGMI有效劑量5.0 mg/kg,分別于再灌注前0.5 h、再灌后1、2、3和6 h時給藥,3 d后取材研究藥物治療時間窗。結(jié)果 2.5、5.0 mg/kg劑量的DGMI改善大鼠再灌注24 h后的神經(jīng)運動功能、減小腦梗死體積、減輕腦水腫、增強缺血腦組織的超氧化物歧化酶(SOD)的活力,減弱肌酸激酶(CK)、乳酸脫氫酶(LDH)的活力,降低丙二醛(MDA)、IL-1β水平。DGMI 5.0 mg/kg在tMCAO大鼠再灌注3 h內(nèi)給藥均改善神經(jīng)運動功能障礙、減小腦梗死體積、減輕腦水腫。結(jié)論 DGMI對大鼠缺血性腦卒中急性期損傷具有保護作用,治療時間窗少于缺血再灌注后6 h,其機制與抗氧化應(yīng)激、抑制炎癥相關(guān)。
[Key word]
[Abstract]
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 respectively. Infact volume, cerebral water content, oxidative stress markers, and IL-1β were evaluated after 72 h of reperfusion. The rats were treated with DGMI 5.0mg/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.
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