Long-term toxicity of modified recombinant human tumor necrosis factor in Macaca mulata  

Long term toxicity of modified recombinant human tumor necrosis factor in Macaca mulatta

作　　者：顾长虹[1] 袁伯俊[1] 陆国才[1] 戴祖瑞[1] 刘俊平[1] 张淑英[1] 张璞[1] 蒋春雷[1] 

机构地区：[1]第二军医大学新药评价中心

出　　处：《中国药理学报》1998年第1期85-88,共4页Acta Pharmacologica Sinica

摘　　要：目的：研究新型重组人肿瘤坏死因子（ｒｈＴＮＦＮＣ）ｉｖ对恒河猴的长期毒性，并与重组人肿瘤坏死因子（ｒｈＴＮＦ）作比较．方法：１６只恒河猴分４组分别每日ｉｖｒｈＴＮＦＮＣ９３和９３ＧＵ／ｍ２１个月和ｒｈＴＮＦ６３ＧＵ／ｍ２１０ｄ，检测其一般症状，血液学，血液化学和尿液生化指标，心电图，特异性抗体，骨髓，对组织器官作病理检查等．结果：ｉｖｒｈＴＮＦＮＣ后除大剂量组出现纳差和部分动物眼睑水肿之外，未见明显的药物性毒性反应，而ｒｈＴＮＦ组除上述反应外，还伴有肝肾受损，红系降低，注射局部有静脉炎及血栓形成等病理改变．此外两种ＴＮＦ均能使猴产生特异性抗体．结论：ｒｈＴＮＦＮＣ对恒河猴的毒性比ｒｈＴＮＦ要小得多．AIM: To study the long term toxicity of modified recombinant human tumor necrosis factor (rhTNF NC) in Macaca mulatta compared with recombinant human tumor necrosis factor (rhTNF). METHODS: rhTNF NC 93, 9 3 GU/m 2, and rhTNF 62 GU/m 2 were injected iv daily to 16 Macaca mulatta for 1 month and 10 d , respectively. Hematologic, chemical, urinalysis values, ECG, specific antibody, bone marrow, and pathologic profile of organs were measured. RESULTS: No more adverse effects of rhTNF NC were found in spite of anorexia in 4 monkeys and palpebral edema in 2 monkeys of 93 GU/m 2 group. Besides, in rhTNF group, the injury of liver and kidneys, the decrease of erythron, the phlebitis, and thrombosis at injection site occurred. Both drugs caused the production of specific antibody. CONCLUSION: No serious adverse effects of rhTNF NC were found in Macaca mulatta . The toxicity of rhTNF NC was much lower than that of rhTNF.

关 键 词：肿瘤坏死因子 恒河猴 毒性试验 

分 类 号：R979.5[医药卫生—药品]