TRAIL参与氧合血红蛋白诱导的脑血管内皮细胞凋亡

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。

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

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.