摘要
目的分析血管紧张素Ang-(1-7)对蛛网膜下腔出血(SAH)后血脑屏障通透性的作用及机制。方法枕大池二次注血法制备SAH大鼠,伊文思蓝(Evans blue)检测Ang-(1-7)处理后SAH大鼠血脑屏障通透性及脑组织含水量;实时荧光定量PCR(RT-PCR)与蛋白免疫印迹法(Western blot)分析脑组织黏连蛋白ICAM-1、VCAM-1的表达。人工血性脑脊液(BCSF)刺激血管内皮细胞(HBMEC),检测细胞通透性及细胞增殖与凋亡情况。结果 Ang-(1-7)可降低SAH大鼠脑组织中Evans blue渗透量及脑组织含水量,具有剂量和时间依赖性,以10^(-5) mol/L Ang-(1-7)处理24h时变化最为显著,SAH大鼠脑组织中ICAM-1、VCAM-1表达水平显著上调。同时Ang-(1-7)作用的BCSF刺激的血管内皮细胞中Evans blue的渗透量明显减少,ICAM-1、VCAM-1的表达水平及细胞增殖活力显著增加,细胞凋亡减少。结论 Ang-(1-7)具有保护蛛网膜下腔出血后血脑屏障通透性作用。
Objective To analysis the effects of Ang-(1-7) on the blood brain barrier permeability after subarachnoid hemor-rhage .Methods SAH-rats were produced by two times injection of blood into cisterna magna .Evans blue was used to detect the the permeability of SAH-rats brains and brain water content .RT-PCR and Western blot were performed to measure the expression of adhesion protein ICAM-1 and VCAM-1 in brains of SAH-rats .The artificial hemorrhagic cerebrospinal fluid (BCSF) was used to stimulate vascular endothelial cells (HBMEC) ,and the proliferation and apoptosis of HBMEC cell were analyzed .Results Ang-(1-7) reduced the content of Evans blue and brain water in brains of SAH-rats in dose and time dependent manner with the most sig-nificant change under the treatment of 10 - 5 mol/L Ang-(1-7) for 24 h (P〈0 .05) .Under the above condition ,the mRNA and pro-tein levels of ICAM-1 and VCAM-1 in brains of SAH-rats were significantly up-regulated (P〈0 .05) ,while the content of Evans blue in HBMEC cells stimulated by BCSF was obviously reduced .Besides ,Ang-(1-7) was observed to increase the expression of ICAM-1 and VCAM-1 in BCSF-stimulated HBMEC cells ,enhance the proliferation of HBMEC cells but reduce their apoptosis . Conclusion Ang-(1-7) plays a protective role in the blood-brain barrier damage induced by subarachnoid hemorrhage .
出处
《重庆医学》
CAS
北大核心
2016年第17期2327-2329,2333,共4页
Chongqing medicine
基金
国家科技惠民计划项目(2013GS500101-15)
中国人民解放军神经创伤防治重点实验室2013开放课题资助项目(NTP2013005)