蓖麻毒素毒性作用机制及防治研究进展

Toxicity and treament of ricin poisoning:a review

蓖麻毒素为提取自蓖麻子的植物毒素,属于Ⅱ型核糖体活性抑制剂,含有A和B亚基(RTA和RTB),通过二硫键相连。RTB与靶细胞表面的糖蛋白或糖脂结合,介导毒素内吞进入细胞并沿逆向转运途径进入内质网,还原释放RTA进入细胞质。在细胞质内RTA通过其RNA核糖酶活性抑制蛋白合成产生细胞毒性。除蛋白合成抑制作用,蓖麻毒素还具有诱导细胞凋亡、细胞因子释放及过氧化作用。蓖麻毒素具有制备成本低廉、性质稳定、多种中毒途径和无特效解毒药等特点。由于它毒性剧烈,作为生物战剂和恐怖剂,严重威胁公共安全。本文针对蓖麻毒素作为恐怖剂应用历史、结构和毒性作用机制、检测方法和特异性抗毒药物研究进行综述。

Ricin is a plant toxin isolated from the seed of the castor plant（Ricinus communis）. As a typical II ribosome inactivating protein,ricin consists of two polypeptide chains named ricin toxin A chain（RTA）and ricin toxin B chain（RTB）,linked via a disulfide bridge. RTB binds to both glycoprotein and glycolipid at the surface of the target cell and mediates ricin to be endocytosed and transported retrogradely to the endoplasmic reticulum. After being reduced and retrotranslocated to the cytosol,RTA mediates its toxicity due to its activity of a RNA N- glycosidases. Aside from its main toxic effect of protein synthesis inhibition,ricin also displays other properties that contribute to its toxicity such as inducing apoptosis,cytokine secreting and peroxidation. Ricin is stable and can be easily isolated. It has many routes of intoxication with no specific antidotes. Due to its natural abundance,remarkable toxicity,and the potential to be used in biological warfare as well as terrorist attacks,ricin has been classified as a Category B biothreat agent. Here we reviewed its history as a biothreat agent,constitution,intoxication mechanism,detection methods and the development of specific antitodes.