出血性蛇毒诱导血管内皮细胞凋亡的成分及作用机制研究进展

出血性蛇毒能专一性诱导血管内皮细胞(vascular endothelial cells，VEC)凋亡，研究人员已从中分离出5种VEC凋亡诱导成份，其中2种为L—aa氧化酶类，3种属于金属蛋白酶／解整联蛋白家族。研究证实前者可通过氧化VEC细胞膜上的L—leu产生H2O2而诱导其凋亡，后者则通过干扰膜整联蛋白与其配体的结合而使VEC凋亡。在由蛇毒诱导的VEC凋亡过程中，p53和bcl-2基因表达增加，且bcl-2的mRNA被剪辑成2条。已证实锚定依赖性信号分子αvβ3和磷脂信号分子PC-PLC参与该过程的信号转导。对该领域进一步研究，有望从蛇毒中纯化出或人工构建出专一地诱导肿瘤血管细胞凋亡的成分。本文总结了出血性蛇毒方面的研究进展。

Progress of Studies on VEC Apoptosis-inducing Proteins in Snake Venom and Its Mechanism-Review

Hemorrhagic snake venom specially induces apoptosis of VEC (vascular endothelial cells). Five apoptosis-inducing proteins had been purified and characterized from crude snake venom. Two of these are L-amino acid oxidase (LAO), the others belong to metalloprotease/disintegrin family. LAO catalyzes H2O2 production by oxidizing some plasma membrane proteins of VEC, disintegrins interfere with binding of integrins with their ligands. The expression of p53 and bcl-2 increases during VEC apoptosis induced by snake venom, moreover, the mRNA of bcl-2 is spliced into two fragments. It has been proved that one of adhesion-dependent signal molecules, alphavbeta3, and one of phospholipid signal molecules, PC-PLC (phosphatidylcholine-specific phospholipase C), are involved in above apoptosis-inducing signal transudation pathway. These results throw light on finding out specific component from protein is snake venom. This component is able to induce tumor vascular endothelial cells apoptosis. This review summarized progress of research on hemorrhagic snake venoms.