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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。
Objective To compare the toxicity of rhTNFαDa and recombinant human tumor necrosis factor α (rhTNFα). Methods Acute toxicity test and long-term toxicity test. Results Acute toxicity test results: LD50 of rhTNFαDa and rhTNFα mice were 0.67 × 109 and 39 × 106IU / m2, respectively. Long-term toxicity test results: The toxic effect of rhTNFαDa is similar to that of rhTNFα. It has a wide range of toxic effects and causes damage to the central nervous system, cardiovascular system, digestive system, hematopoietic system, male reproductive system and kidney. Continuous injection can cause cachexia. The toxic effect of rhTNFαDa medium dose group (53 × 106IU / m2) was equivalent to or slightly lower than that of rhTNFα (5.3 × 106IU / m2). Conclusion The modified rhTNFαDa has the similar toxicological effects as rhTNFα, but the degree of toxicity is reduced by one order of magnitude compared with that of rhTNFα.