摘要
产气荚膜梭菌ε毒素(Epsilon toxin,ETX)由B、D型产气荚膜梭菌产生并分泌至宿主动物体内,在临床上主要症状为肠毒血症.ETX属于以七聚体形式存在的β-样成孔毒素,它能够形成由14个β折叠片组成的"β-桶状"结构,这个"β-桶状"结构可以插入真核细胞的质膜形成穿孔.在细胞水平,ETX能够迅速使细胞膜肿胀、多种细胞器破坏,最终导致靶细胞的坏死.在哺乳动物体内,ETX能够使哺乳动物血管产生水肿,从而穿透血脑屏障而聚积在动物肾和脑中,导致机体随着谷氨酸盐的释放而产生过度兴奋,这一系列反应的发生可以引起机体出现脑水肿和肾衰竭,最终导致动物的死亡.目前,ETX备受关注的主要原因不仅仅因为它是一种β-样成孔毒素,而是可以作为潜在的一种工具类药物,经改造后可以携带治疗药物在短时间内靶向性地到达哺乳动物脑和中枢神经系统,继而为脑和中枢神经系统疾病的治疗提供新的方向.结合国内外相关研究,对ETX细胞毒机制及致病机理进行了综和评述.
Epsilon toxin (ETX) ,a pore‐forming toxin secreted by type B and D strains of Clostridium perf ringens ,mediates severe enterotoxemia in their host .ETX forms a heptamer which consists of aβ‐barrel of 14 amphipathicβ‐strands through the plasma membrane of eukaryotic cells .At the cellu‐lar level ,ETX can quickly make the cell membrane swelling ,damage various organelles ,eventually lead target cells to necrosis .ETX binds to endothelial cells of kidney and brain capillary vessels be‐fore passing through the blood‐brain barrier .Moreover ,it induces perivascular oedema and perme‐ates into and accumulates at brain and kidney .Therefore ,ETX induces releasing of glutamate and other transmitters ,leading to firing of neural network and resulting in animal death .At present ,the main reason for ETX to be concerned is not because it is a beta‐barrel pore forming toxin ,but is that it can be used as a tool for potential drugs .After reconstruction ,ETX is thought to be able to carry therapeutic drug in a short time arrived in mammalian brain and central nervous system .This think‐ing provides a new direction to the brain and central nervous system disease treatment .Therefore , based on the existing knowledge worldwide ,the cytotoxicity mechanism and pathogensis of ETX are summarized and review ed .
出处
《辽宁师范大学学报(自然科学版)》
CAS
2015年第2期219-224,共6页
Journal of Liaoning Normal University:Natural Science Edition
基金
国家重点基础研究发展计划(973计划)项目(2013CB835304)
全国海洋公益项目(201305016)
国家自然科学基金项目(31170353
31202020)
大连市科技计划项目(2013E11SF056)