摘要
目的比较重组人肿瘤坏死因子α衍生物A(rhTNFαDa)与重组人肿瘤坏死因子α(rhTNFα)的毒性。方法急性毒性试验和长期毒性试验。结果急性毒性试验结果:rhTNFαDa和rhTNFα的小鼠LD50分别为0.67×109和39×106IU/m2。长期毒性试验结果:rhTNFαDa的毒性作用性质与rhTNFα相似,毒性作用广泛,对中枢神经系统、心血管系统、消化系统、造血系统、雄性生殖系统、肾脏均有损害,连续注射且会引起恶病质。rhTNFαDa中剂量组(53×106IU/m2)的毒性作用程度与rhTNFα(5.3×106IU/m2)相当或略低。结论改构后的rhTNFαDa的毒性作用性质与rhTNFα相似,但毒性作用程度与rhTNFα相比却下降了1个数量级。
URPOSE To compare the toxicity between derivative A of recombinant human tumor necrosis factor α (rhTNFαDa) and original recombinant human tumor necrosis factor α(rhTNFα).METHODS Acute toxic test and chronic toxic test were used. RESULTS The results demonstrated that LD50 of rhTNFαDa and rhTNFα are 0.67×109IU/m2 and 39×106IU/m2 separately, and the nature of toxicity of rhTNFαDa is similar to that of original rhTNFα with a wide spectrum such as on the central nervous system, cardiovascular system, digestive system, hematopoietic system, male genital system and kidney. Cachexia appeared after a consecutive injections of rhTNFαDa and rhTNFα. The toxicity of 53×106IU/m2 rhTNFα Da on monkeys is equal to or less than that of 5.3×106IU/m2 rhTNFα.CONCLUSIONS The nature of toxicity of rhTNFαDa is similar to that of original rhTNFα, while the toxicity of rhTNFαDa is only one tenth of rhTNFα.
出处
《上海医科大学学报》
CSCD
1998年第3期201-204,共4页
Journal of Fudan University(Medical Science)