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作 者:赵品楠 罗龙龙 ZHAO Pinnan;LUO Longlong(State Key Laboratory of National Security Specially Needed Medicines,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)
机构地区:[1]军事科学院军事医学研究院毒物药物研究所,国家安全特需药品全国重点实验室,北京100850
出 处:《中国药理学与毒理学杂志》2024年第4期304-313,共10页Chinese Journal of Pharmacology and Toxicology
基 金:国家自然科学基金(82204262);北京市科技新星人才项目(Z211100002121020);北京市科技新星交叉课题(20220484216)。
摘 要:产气荚膜梭菌(CP)是一种常见的人兽共患病菌,广泛存在于自然界中,其分泌的外毒素给人类健康和畜牧业造成较大影响和损失。CP最主要的致病毒素为α,β,ε和τ毒素及肠毒素和坏死性肠炎B样毒素,其导致的疾病各不相同。抗生素治疗是目前治疗CP感染的主要手段,但由于耐药性不断增长,控制CP感染愈发困难。近年来随着基因工程技术的快速发展,针对不同外毒素的疫苗或抗体有可能成为应对CP感染的新一代免疫治疗手段。研究表明,针对CPα毒素的疫苗可预防小鼠A型CP感染;抗α毒素的单链抗体、双价单链抗体和纳米抗体等,可与α毒素特异性结合,有效中和α毒素的磷脂酶C活性,在小鼠模型中对致死量α毒素攻击具有保护作用。本文简述CP的主要致病因子、致病机制和基因工程抗体治疗研究进展,为CP感染防治提供参考。Clostridium perfringens(CP)is a common zoonotic pathogen that widely exists in nature and takes a heavy toll on human health and animal husbandry through its secreted exotoxins.The main pathogenic toxins of CP areα,β,εandτtoxins,enterotoxins and necrotizing enteritis B-like toxins.The diseases caused by these toxins vary.Antibiotic therapy is currently the main method for the treat⁃ment of CP infection,but due to the growing drug resistance,it is increasingly difficult to control CP infection.In recent years,based on the rapid development of genetic engineering technologies,vaccines or antibodies against different exotoxins may become a new generation of immunotherapy for CP infec⁃tion.Studies have shown that the vaccines against CPα-toxin can prevent type A CP infection in mice.Anti-α-toxin single chain antibodies,bivalent single chain antibodies and nano-antibody can specifically bind toα-toxin,effectively neutralize the phospholipase C activity ofα-toxin,and protect mice against lethal doses ofα-toxin challenge.This article reviews the main pathogenic factors and mechanisms of CP and the research progress in genetic engineering antibody therapies so as to provide reference for the prevention and treatment of CP infection.
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