中文摘要：

目的探讨环孢菌素A（cyclosporine A,Cs A）对小鼠脑缺血再灌注后血脑屏障的影响及其可能机制。方法通过线栓法对C57BL/6J及载脂蛋白E基因敲除（Apo E-/-）小鼠建立大脑中动脉栓塞（middle cerebral artery occlusion,MCAO）模型,用不同剂量（10、20 mg/kg）Cs A进行干预,并将两种小鼠各自分为5组：假手术组（Sham）、手术组（I/R）、溶剂组（Vehicle）、小剂量组（10 mg/kg Cs A）及大剂量组（20 mg/kg Cs A）。观察小鼠脑缺血再灌注后神经功能评分、梗死灶体积、脑组织水含量及伊文思蓝漏出量的变化情况,并用Western blot检测各组p-Akt及Claudin-5蛋白表达量的变化。结果 1神经功能评分结果显示：MCAO后小鼠出现严重的神经功能障碍,经Cs A干预后其损伤情况明显缓解,且大剂量组优于小剂量组（P〈0.05）;2小鼠在脑缺血再灌注后表现出现严重的脑水肿、脑梗死及伊文思蓝渗漏,且各组Apo E-/-小鼠表现得比C57小鼠更为明显（P〈0.05）,而Cs A能缓解这些症状,且大剂量组效果明显优于小剂量组（P〈0.05）;3Western blot检测结果显示：Apo E-/-小鼠脑组织中p-Akt蛋白表达量高于C57小鼠,而Claudin-5相对较低（P〈0.05）。经MCAO处理后各组小鼠均出现p-Akt蛋白表达明显增高从而引起Claudin-5减少（P〈0.05）,Cs A干预后,该效应出现逆转,且大剂量组的效果明显优于小剂量组（P〈0.05）。结论 Cs A可保护脑缺血再灌注后血脑屏障的损伤,从而起到改善预后的作用,其机制与PI3K/Akt信号通路有关,而Apo E-/-可通过该途径加重脑梗死。

英文摘要：

Objective To determine the effect of cyclosporine A（ Cs A） on blood-brain barrier after cerebral ischemia-reperfusion（ I / R） injury in mice and investigate its possible mechanism. Methods Middle cerebral artery occlusion（ MCAO） model were established by Longa＇s method in C57 BL /6J mice and apolipoprotein E knockout（ Apo E- /-） mice. Then the C57BL/6J mice and Apo E- /-mice were assigned into5 groups,that is,sham operation group（ n = 5）,I / R group（ n = 14）,vehicle group（ n = 14）,low- and high- dose Cs A intervention groups（ 10 and 20 mg / kg,given intraperitoneally in 15 min,and 24 and 48 h after model establishment,n = 14）. After neurological function was evaluated,the mice were sacrificed in 1,3,5 and 7 d after surgery,and the brain tissues were harvested for infarct volume,brain water content,and the permeability of blood-brain barrier（ Evans blue leakage）. Western blotting was used to detect the expression levels of p-Akt and Claudin-5. Results（ 1） Neurological function evaluation showed that MCAO resulted in severe neurological dysfunction in the mice,but Cs A intervention obviously attenuated the injury,with the high-dose group superior to the low-dose group（ P〈0. 05）.（ 2） Cerebral I / R injury induced severe cerebral edema,cerebral infarction and reduced leakage of blood-brain barrier,and the Apo E- /-mice were injured more heavily than the C57 mice（ P〈0. 05）. However,Cs A alleviated the symptoms,and the effects were more significant in the high- than low-dose intervention group（ P〈0. 05）.（ 3） Western blot results showed that the protein level of p-Akt was higher,while that of Claudin-5 was lower in the brain tissue of normal Apo E- /-mice than normal C57 BL /6J mice（ P〈0. 05）. After MCAO,the expression of p-Akt was significantly increased and then Claudin-5 was decreased（ P〈0. 05）. Cs A inhibited the process,and the high-dose group had greater effect than the low-dose group（ P〈0. 05）. Conclusion Cs A repairs the bloodb