目的:通过复制小鼠急性不完全性脑缺血模型,研究Ento-Ⅰa涂膜剂对脑缺血的保护作用。方法:140只小鼠分为2批进行实验,每批70只。将70只小鼠随机分为7组,每组10只,分别为假手术组、Ento-Ⅰa涂膜剂组(37.50mg· kg-1、18.75mg·kg-1、9.38mg·kg-1)、生理盐水模型组、基质模型组、尼莫地平组(18mg·kg-1,ig)。Ento-Ⅰa涂膜剂预防给药7 d后,测定小鼠结扎双侧颈总动脉带迷走神经后的存活时间及其脑组织SOD活性、MDA含量、EB含量。结果:Ento-Ⅰa涂膜剂在剂量为18.75 mg·kg-1时,可以明显延长小鼠结扎双侧颈总动脉带迷走神经后的存活时间(P<0.05),延长率为39.55%;在剂量为37.50mg·kg-1时效果最佳(P<0.01),小鼠存活时间的延长率为45.15%,与阳性药尼莫地平(18 mg ·kg-1,延长率43.96%)相当。与基质模型组比较,Ento-Ia涂膜剂18.75、37.50 mg·kg-1剂量组均可提高脑组织内SOD活性并能减少MDA含量(中剂量组,P<0.05;高剂量组P<0.01);同时,Ento-Ia涂膜剂能显著降低小鼠急性不全性脑缺血小鼠脑组织EB含量(P<0.05)。结论:Ento-Ia涂膜剂经皮给药可对小鼠急性不完全性脑缺血诱发的脑损伤有明显的保护作用,其机制可能通过干预脑缺血后脑组织的氧化应激及其保护血脑屏障有关。
Objective To investigote the protective effect of Ento-Ⅰa Plaster on acute mice incomplete cerebral ischemia.Methods 140 mice were divided into two batches to carry on the experiment,each batch 70.70 rats were randomly divided into 7 groups,10 in each group,the sham operation group,the Ento-Ⅰa coating group (37. 50mg·kg-1、18. 75mg·kg-1、9. 38mg·kg-1 ),the saline model group,the matrix model group,the nimodipine group (18 mg·kg-1 ,ig).Ento-Ia plastic was given prophylactically for 5 days, establishment mice acute incomplete cerebral ischemia model by total bilateral carotid artery ligation in mice with vagus nerve,record sur-vival time of mice after ischemia and the determination of mouse brain tissue SOD activity,MDA content and the content of Evans blue. Results This research shows that Compared with the model group matrix,Ento-Ia plastic can significantly prolong the survival time of mice after ligation of bilateral common carotid artery with vagus nerve at a dose of 18. 75 mg·kg-1 (P〈0. 05),the extension rate was 39. 55%;At a dose of 137. 50 mg·kg-1 ,the effect was the best (P〈0. 01),prolonged survival time of mice was 45. 15%,com-pared with the positive drug nimodipine (18mg·kg-1 ,the elongation rate of 43. 96%). Compared with the matrix model group,Ento-Ia plastic at the dose of 18. 75 and 37. 50mg·kg-1 dose group could increase the brain tissue SOD activity and reduce MDA content (middle dose group,P〈0. 05;high dose group P〈0. 01 ). At the same time,Ento-Ia plastic can significantly reduce the cerebralcapillary permeability (P〈0. 05),which is equivalent to the nimodipine group (P〉0. 05).Conclusion Ento-Ⅰa plastic has obvious protective effect for transdermal delivery of mice with acute incomplete cerebral ischemia induced brain injury,its mechanism may be through the intervention of brain tissue of cerebral ischemia oxidative stress and protection of BBB.