抗胸腺细胞球蛋白/抗淋巴细胞球蛋白的药理毒理学及其临床研究

Pharmacological toxicology and clinical studies of anti-themocyte globulin and anti-lymphocyte globulin

抗胸腺细胞球蛋白(anti-themocyte globulin,ATG)和抗淋巴细胞球蛋白(anti-lymphocyte,ALG)是一种含有抗淋巴细胞活性的免疫球蛋白液体或冻干制剂。ATG/ALG作为免疫抑制剂在肾移植、心脏移植、肝移植、骨髓移植及重型再生障碍性贫血(severe aplastic anemia,SAA)的治疗方面已被广泛应用,且效果显著。ATG/ALG的主要生物学效应在于细胞毒T淋巴细胞。ATG/ALG对T淋巴细胞的直接作用主要通过下列途径:补体介导的T细胞溶解;阻断信号传导通路;诱导细胞凋亡;抑制细胞黏附;活化细胞的调理素化。ATG/ALG能有效地预防急性排斥反应,可使绝大多数耐激素的难治性急性排斥反应逆转。本文通过检索国内外有关ALG/ATG文献,对其药效学、药理学、药动学、毒理学、安全性、不良反应以及临床研究进行综述,以期能为ALG/ATG的生产工艺优化和合理的临床应用提供参考。

Anti-thymocyte globulin(ATG)and anti-lymphocyte globulin(ALG)are liquid or lyophilized immunoglobulin preparations with anti-lymphocyte activity.As immunosuppressants,ATG/ALG have been widely used in kidney transplantation,heart transplantation,liver transplantation,bone marrow transplantation and therapy of severe aplastic anemia(SAA).The main biological effects of ATG/ALG lie in cytotoxic T lymphocytes.The direct effects of ATG/ALG on T lymphocytes are mainly through the following pathways:complement-mediated T cell lysis,blocking signal transduction pathways,inducing apoptosis;inhibiting cell adhesion and activating cell modulation.ATG/ALG may effectively prevent acute rejection and reverse the majority of hormone-resistant refractory acute rejection.By searching the domestic and foreign literatures related to ALG/ATG,in this reviews we study the pharmacodynamics,pharmacology,pharmacokinetics,toxicology,safety,adverse reactions and clinical researches of ALG/ATG to provide references for the optimization of production processes and rational clinical applications.