体外培育抗苏拉灭伊氏锥虫克隆

Development of Suramin-Resistant Clones of Trypanosomaevansi in vitro by Drug Exposure

将３个苏拉灭敏感的伊氏锥虫原种的克隆连续培养于改良Ｂａｌｔｚ无细胞培养系统中，通过逐步提高培养基中苏拉灭的含量，培育了３个抗苏拉灭的伊氏锥虫克隆─ＪＧｃ１－１６０、ＪＸ－１ｃ１－１６０和ＺＪｃ１－１４０。它们体外药敏试验的ＩＣ５０依次为３５８．５、４１２．３和２４６．４μｇ／ｍＬ，是各自亲本克隆的１２９２．５、１８７４．１和１７６０．ｏ倍；小鼠治疗试验的ＣＤ１００，对免疫功能正常小鼠依次为８０、１２０和３０ｍｇ／ｋｇ，为各自亲本克隆的５．３、８．０和３．０倍，对免疫抑制小鼠为２５０、３００和１００ｍｇ／ｋｇ，分别是相应免疫正常小鼠的３．１、２．５和３．３倍。试验结果表明，抗锥虫药治疗剂量不足和宿主免疫功能不全是导致产生抗药虫株的重要因素，各自既可单独发挥作用，又可相互协同。本文报道了体外培育伊氏锥虫抗药虫株的方法，这一方法对研究锥虫抗药性具有重要作用。

By exposure to gradually increasing concentrations of suramin in modi- fied Baltz's cell-free culture system,3 suramin-resistant clones(JGc1-160, JX-1c1-160and ZJc1-l4o)were derived from 3 suramin-sensitive strains of Trypanosoma evansi(JGc1,JX-lc1 and ZJc1 )over a period of 550 days. The IC50 of in vitro drug susceptibility test in JGc1-160 was 358.5 μg/mL, and 1292.5 times as much as that of its parent strain; in JX- lc1-160 , 412.3μg/mL and 1874.1 times; in ZJc1-140 , 246.μg/mL and 1760.0 times.The CD100 for intact mice and immunosuppressed mice infected with JGc1-160 were 80 and 250 mg/kg respectively, the doses for both groups of mice infected with JX-1c1-160 were 120 and 300 mg/kg; and for those infected with ZJc1-140 were 30 and 100 mg/kg;The ra-tios of CD10O for immmunosuppressed mice to those for intact mice were 3.13,2.5 and 3.33 in JGc1-160,JX -1c1-160 and ZJc1-140,respectively. These results suggested that besides the inadequacy of curative dosage of trypanosomicide, the deficiency of host immune de- fence appeared to be an important factor resulting in the development of drug resistance. Both these factors play the role alone or together.