谷胱甘肽S转移酶的安全性评价  

Safety Evaluation of Glutathione S Transferase

作　　者：刘玉莹 伍树明 姜绪林 银飞 陈丹 张贵锋[2,3] 张红彩 张海江 刘永江 LIU Yu-ying;WU Shu-ming;JIANG Xu-lin;YIN Fei;CHEN Dan;ZHANG Gui-feng;ZHANG Hong-cai;ZHANG Hai-jiang;LIU Yong-jiang(Beijing Health Guard Biotechnology Inc.,Beijing 100176,China;State Key Laboratory of Biochemical Engineering,Institute of Process Engineering,Chinese Academy of Sciences,Beijing 100190,China;School of Chemical Engineering,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]北京康乐卫士生物技术股份有限公司,北京100176 [2]中国科学院过程工程研究所生化工程国家重点实验室,北京100190 [3]中国科学院大学化学工程学院,北京100049

出　　处：《药物生物技术》2023年第2期130-135,共6页Pharmaceutical Biotechnology

摘　　要：为了评价谷胱甘肽S转移酶(GST)的安全性,文章通过单次给药毒性试验和免疫毒性试验对GST的毒性进行了研究。采用单次给药毒性试验的方法,分别准备雌雄ICR小鼠各10只,采用最大给药量法,尾静脉注射GST,单次给药最大给药剂量为2.75 mg/kg,观察ICR小鼠的中毒症状及中毒症状出现的时间、表现程度、发展过程、动物死亡前的特征及死亡时间等。采用免疫毒性试验的方法,50只小鼠随机分为5组,通过迟发型超敏反应方法,观察GST对迟发超敏反应的影响;40只小鼠随机分为4组,通过溶血空斑试验方法,评价其对小鼠体液免疫功能影响。单次给药毒性试验结果表明:和生理盐水对照组相比,实验组小鼠一般状况良好,体重逐渐增加,给药组动物各个脏器均未发现异常表现情况。免疫毒性试验结果表明:与溶剂对照组相比,体重未见明显降低,实验组动物胸腺指数和脾指数均无显著性差异,但剂量为1500 ng/只的GST给药组,无论是否含有佐剂,其肿胀度和溶剂对照组均有显著性差异(P≤0.05);GST给药各组动物溶血空斑计数和对照组比较无显著差异(P>0.05)。GST的单次给药的最大耐受剂量(MTD)大于2.75 mg/kg,对动物的细胞免疫和体液免疫均无抑制作用,但1500 ng/只剂量下可增强2,4-二硝基氟苯诱导的动物迟发超敏反应强度。In order to evaluate the safety of glutathione S transferase(GST),the toxicity of GST was studied by single dose toxicity test and immunotoxicity test.Adopted the methods of single dose toxicity test,10 male and female ICR mice were prepared,and GST was injected into tail vein by the maximum dose method.The maximum dose of GST was 2.75 mg/kg.The symptoms of poisoning,the time of occurrence of poisoning symptoms,the degree of manifestation,the development process,the characteristics of the animals before death and the time of death of ICR mice were observed.Adopted the methods of immunotoxicity test,50 mice were randomly divided into five groups and the effect of GST on delayed hypersensitivity was observed by delayed hypersensitivity method.40 mice were randomly divided into four groups and the effect of hemolytic plaque test on humoral immune function was evaluated.Singledose toxicity test showed that compared with the normal saline control group,the mice in the experimental group were generally in good condition and gradually gained weight.No abnormal manifestations were found in each organ of the animals in the administration group.Immunotoxicity test showed that compared with the solvent control group,there was no significant decrease in body weight,and there was no significant difference in thymus index and spleen index in the experimental group.However,the swelling degree of the GST group at the dose of 1500 ng/mouse was significantly different from that of the solvent control group,regardless of whether it contained adjuvant or not(P≤0.05).There was no significant difference in hemolytic plaque count between GST group and control group(P>0.05).The maximum tolerated dose(MTD)of a single dose of GST was greater than 2.75 mg/kg,which had no inhibitory effect on cellular and humoral immunity of animals,but 1500 ng/mouse can enhance the intensity of delayed hypersensitivity induced by 2,4-dinitrofluorobenzene in mice.

关 键 词：谷胱甘肽S转移酶 单次给药毒性试验 最大耐受剂量 免疫毒性试验 迟发型超敏反应 溶血空斑试验 安全性 

分 类 号：R965.3[医药卫生—药理学]