论文部分内容阅读
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。
Objective To investigate the effect of cyclosporine A (CsA) on the blood-brain barrier after cerebral ischemia-reperfusion in mice and its possible mechanism. Methods The middle cerebral artery occlusion (MCAO) model of C57BL / 6J and ApoE - / - mice was established by the suture method. The rats were treated with 10,20 mg / kg CsA). The mice were divided into 5 groups: Sham group, operation group (I / R), vehicle group, low dose group (10 mg / kg Cs A ) And high-dose group (20 mg / kg Cs A). The changes of neurological function scores, infarct volume, brain water content and Evans blue leakage were observed after cerebral ischemia-reperfusion in mice. The expression of p-Akt and Claudin-5 protein in each group were detected by Western blot. Results 1 Neurological score showed that severe neurological dysfunction was found in mice after MCAO. The injury was relieved after CsA intervention, and the high dose group was better than the low dose group (P <0.05) Severe cerebral edema, cerebral infarction and Evans blue leakage were observed after ischemia-reperfusion, and Apo E - / - mice in each group showed more obvious effects than C57 mice (P <0.05), whereas CsA (P <0.05). Western blot results showed that the expression of p-Akt protein in Apo E - / - mice was higher than that in C57 mice Claudin-5 was relatively low (P <0.05). After MCAO treatment, the expression of p-Akt in each group was significantly increased, which led to the decrease of Claudin-5 (P <0.05). After CsA intervention, the effect reversed, and the effect of high dose group was obviously better than that of low dose Group (P <0.05). Conclusion CsA can protect the blood-brain barrier after cerebral ischemia-reperfusion, and thus play a role in improving prognosis. The mechanism of CsA is related to the PI3K / Akt signaling pathway, and Apo E - / - may increase cerebral infarction.