小鼠脑缺血-再灌注损伤后泊洛沙姆188与银杏内酯B联合应用研究*

目的：探讨泊洛沙姆188与银杏内酯B联合应用对小鼠脑缺血-再灌注损伤的保护作用。方法：以线栓造成小鼠脑组织缺血状态,线栓移除前5min经尾静脉单次注射泊洛沙姆188（0.4g/kg）,银杏内酯B（20mg/kg）或两药的混合溶液,24小时后评价小鼠神经症状并测定脑梗死面积和脑含水量。另一批小鼠在静脉注射给药后再每天腹腔注射上述等效剂量药物,24天后统计各组存活状况,绘制生存曲线;采用爬杆试验、悬挂试验测试小鼠肢体运动功能。结果：生理盐水组小鼠脑梗死面积为35.49%±8.31%,P188组、GB组以及合用组的脑梗死面积分别减少为27.76%±6.41%,25.51%±5.81%和21.16%±8.67%,P188与GB合用组比药物单用组的脑梗死面积更小,差异有统计学意义（P<0.05）。生理盐水组小鼠24天后的生存率为38.89%,P188组,GB组以及合用组小鼠的生存率分别为50%,53.57%和69.21%。P188与GB合用组与药物单用组相比,生存期明显延长,差异均有统计学意义（P<0.05）。P188组、GB组以及药物合用组T/turn分别为6.22秒,6.56秒和5.25秒,T/floor分别为15.50秒,14.88秒和13.25秒,P188和GB合用组与药物单用组相比,T/turn和T/floor均显著缩短,差异均有统计学意义（P<0.05）。与泊洛沙姆188和银杏内酯B单用相比,联合用药能进一步降低脑梗死面积,延长生存期,增强小鼠肢体的运动功能。结论：泊洛沙姆188与银杏内酯B合用能够增强对小鼠脑缺血-再灌注损伤的保护作用。

The protective effects of a combination of Poloxamer 188 and Ginkgolide B against the cerebral ischemia-reperfusion injury in mice

Objective: To explore the protective effects of combined Poloxamer 188 (P188) and Ginkgolide B (GB) in the mice cerebral ischemia-reperfusion model. Methods: The mouse cerebral ischemia-reperfusion model was established by intraluminal occlusion of middle cerebral artery occlusion (MCAO) using monofilament. P188 (0.4g/kg), GB (20 mg/kg) or combination of the two medicines were intravenously injected 5min before reperfusion, 24h later mice were sacrificed to determine the infarct size by using of TTC staining, brain water content and neurological symptoms. Another batch of MCAO mice were used to assess the long-term protective effects by intraperitoneal injection of above medicines once a day for 24 days, the survival curve was made, motor function was evaluated with wire hanging test and pole test. Results: Compared with P188 or GB alone, a combination of P188 and GB significantly ameliorated neurological symptoms and reduced the infarct size, the brain edema 24 h after cerebral ischemia/reperfusion injury. Similarly, in the long-term outcome study, a combination of P188 and GB significantly increased survival rate and alleviated motor impairments. Conclusions: The combination of P188 and GB had greater protective effects against the cerebral ischemia/reperfusion injury than that of P188 or Ginkgolide B alone.