Protection of Diterpene Ginkgolides Meglumine Injection on acute injury of ischemic stroke in rats / 药物评价研究

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 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.