TRAIL参与氧合血红蛋白诱导的脑血管内皮细胞凋亡  

The participation of TRAIL in oxyhemoglobin-induced apoptosis of vascular endothelial cells

作　　者：秦怀州[1] 李立宏[1] 王梁[1] 宗建海[1] 刘华峰[1] 王举磊[1] 高国栋[1] 

机构地区：[1]第四军医大学唐都医院神经外科,陕西西安710038

出　　处：《中华神经外科疾病研究杂志》2009年第2期140-143,共4页Chinese Journal of Neurosurgical Disease Research

摘　　要：目的目前对自发性蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的机制尚不十分清楚,研究认为脑血管内皮细胞的凋亡发挥了重要作用。本实验探讨了肿瘤坏死因子相关凋亡诱导配体(TRAIL)及caspase3在血管内皮细胞凋亡中作用。方法在离体培养的脑血管内皮细胞中,观察给予氧合血红蛋白(OxyHb)处理以及给予caspase3拮抗剂或TRAIL后,运用实时荧光定量聚合酶链反应(PCR)和Western blot检测两者在mRNA和蛋白水平表达的改变。结果和生理盐水阴性对照相比,单纯OxyHb处理以及OxyHb+TRAIL处理后,血管内皮caspase3表达均显著升高(P<0.05)。TRAIL能够上调OxyHb刺激诱导的caspase3表达(P<0.05)。和生理盐水对照组相比,OxyHb处理后,血管内皮TRAIL表达显著上调(P<0.05)。但是,和OxyHb处理相比,caspase3拮抗剂Ac-DEVD-CHO(ADC)不能明显改变OxyHb刺激诱导的TRAIL蛋白的表达上调(P>0.05)。结论TRAIL能够促进SAH后OxyHb刺激导致的内皮细胞凋亡。在凋亡的级联反应过程中,TRAIL能够活化下游caspase3,从而启动凋亡过程。因此,TRAIL及其受体在SAH后CVS的发生、发展过程中可能有着重要作用。Objective To investigate the role of tumor necrosis factor （TNF）-related apoptosis-inducing ligand （TRAIL） and caspase 3 in the apoptosis of vascular endothelial cells. Methods The changes of TRAIL and caspase 3 in cultured vascular endothelial ceils were observed by real-time Polymerase Chain Reaction （PCR） and Western blot after treated with oxyhemoglobin （ OxyHb ） and TRAIL or caspase 3 inhibitor. Results Compared with the saline control, the expression of caspase 3 in the endothelial cells in single treatment group of OxyHb and OxyHb ＋ TRAIL was significantly increased. Furthermore, TRAIL could increase OxyHb-induced upregulation of caspase 3. Compared with the saline control, the expression of TRAIL was significantly increased by OxyHb, which could not be influenced by caspase 3 inhibitor. Conclusion These results indicate that TRAIL can promote OxyHb-induced apoptosis after SAH. And TRAIL can activate down-stream caspase 3 and the process of apoptosis. So TRAIL and its receptor may play a big role in CVS after spontaneous subarachnoid hemorrhage.

关 键 词：TRAIL CASPASE 3 氧合血红蛋白 脑血管痉挛 凋亡 

分 类 号：R743.35[医药卫生—神经病学与精神病学]