GMDTC驱镉剂量研究

发布时间：2018-06-15 08:52

  本文选题：N-( + -五羟基己基)-(N-二取代甲酸钠基)-L-甲硫氨酸钠　； 参考：《中国职业医学》2017年02期

【摘要】：目的探讨静脉滴注驱镉剂N-(2,3,4,5,6-五羟基己基)-(N-二取代甲酸钠基)-L-甲硫氨酸钠(GMDTC)不同剂量下的驱镉效果。方法雄性新西兰兔随机分为空白对照组、GMDTC高剂量对照组、模型对照组、依地酸钠钙(EDTA)对照组和GMDTC低、中、高剂量组,每组5只。空白对照组和GMDTC高剂量对照组新西兰兔分别经耳缘静脉予0.90%氯化钠注射液,模型对照组、EDTA对照组和3个GMDTC剂量组新西兰兔分别经耳缘静脉予浓度为2μmol/kg氯化镉及浓度为40μmol/kg的β-巯基乙醇的混合溶液,给药量为5.0 mL/kg体质量,1次/d,连续5 d。于造模第41天即治疗第1天,空白对照组和模型对照组新西兰兔均经耳缘静脉予0.90%氯化钠注射液250 mL,EDTA对照组新西兰兔予剂量为93.5 mg/kg体质量的EDTA溶液,GMDTC高剂量对照组和3个GMDTC剂量组新西兰兔分别予剂量为108.0、12.0、36.0、108.0 mg/kg体质量的GMDTC溶液,1次/d,6次/周,连续4周。检测各组新西兰兔治疗前后尿β_2-微球蛋白(β_2-MG)、肾镉、血镉和尿镉水平。结果实验期间,新西兰兔体质量随饲养时间的增加而增加(P0.01)。模型对照组、EDTA对照组和3个GMDTC剂量组新西兰兔治疗前尿β_2-MG水平均高于空白对照组(P0.05)。GMDTC中、高剂量组新西兰兔治疗后肾镉水平均低于模型对照组和EDTA对照组(P0.05)。EDTA对照组和3个GMDTC剂量组新西兰兔治疗后的血镉水平均低于同组治疗前(P0.05),且均低于治疗后的模型对照组(P0.05);GMDTC中、高剂量组和EDTA对照组新西兰兔治疗后血镉水平两两比较,差异均无统计学意义(P0.05)。治疗后各时间点(治疗后第1、6、8、13、15、20、22和28天)的新西兰兔尿镉水平,在EDTA对照组和3个GMDTC剂量组均低于同时间点模型对照组(P0.05);治疗后除第20和22天外,其余6个时间点新西兰兔尿镉水平均随GMDTC剂量的增加而增加(P0.05)。GMDTC低、中、高剂量组新西兰兔治疗后血镉驱除率分别为70.06%、74.86%和78.05%,肾镉驱除率分别为14.27%、27.95%和61.24%。结论 GMDTC静脉滴注剂量为108.0 mg/kg体质量对镉中毒兔模型(相当于人用剂量36.0 mg/kg体质量)的驱镉效果显著,未见明显毒性反应,具备成药性基本要求。
[Abstract]:Objective to investigate the effect of intravenous infusion of N-dihydroxy hexyl 6-pentahydroxy hexyl disubstituted sodium formate-L-methionine sodium methionine (GMDTC) at different dosages. Methods male New Zealand rabbits were randomly divided into control group (n = 5), model control group (n = 5), EDTA control group (n = 5) and low, medium and high dose group (n = 5). New Zealand rabbits in blank control group and GMDTC high dose control group were treated with 0.90% sodium chloride injection through auricular vein, respectively. New Zealand rabbits were treated with 2 渭 mol/kg cadmium chloride and 40 渭 mol/kg 尾 -mercaptoethanol via auricular vein in model control group and three GMDTC groups, respectively. The dose was 5.0 mL / kg body weight per day for 5 days. On the 41st day of the model, that is, the first day of treatment, The New Zealand rabbits in the blank control group and the model control group were given 0.90% sodium chloride injection 250mL EDTA through the auricular margin vein. The New Zealand rabbits in the control group were given 93.5 mg/kg volume weight EDTA solution, the high dose control group and the three GMDTC dose groups were given New Zealand rabbit scores. Do not give a dose of 108.0% 12.0% 36.0108.0 mg/kg body mass per day for 6 times per week, 4 weeks in a row. Before and after treatment, the levels of urine 尾 2-MGG, renal cadmium, blood cadmium and urine cadmium in New Zealand rabbits were measured. Results during the experiment, the weight of New Zealand rabbits increased with the increase of feeding time. The levels of urinary 尾 2-MG in the EDTA control group and three GMDTC groups were higher than those in the blank control group before treatment. The levels of renal cadmium in the high dose group were lower than those in the model control group and the EDTA control group, and the blood cadmium levels in the three GMDTC groups were lower than those in the same group before and after treatment, and were lower than those in the model control group after treatment. There was no significant difference in blood cadmium levels between high dose group and EDTA control group after treatment. The levels of urinary cadmium in New Zealand rabbits at each time point after treatment (day 1, 6, 8, 13, 15, 20, 22 and 28 days) were lower in EDTA control group and 3 GMDTC groups than in model control group at the same time point (P0.05), except for the 20th and 22nd days after treatment. In the other six time points, the urinary cadmium levels of New Zealand rabbits increased with the increase of GMDTC dose. The blood cadmium removal rates were 70.066.86% and 78.05%, respectively, and the renal cadmium removal rates were 14.277.95% and 61.2445%, respectively. Conclusion GMDTC intravenous infusion dose of 108.0 mg/kg body mass has significant effect on cadmium displacement in rabbit model of cadmium poisoning (equivalent to human dose of 36. 0 mg/kg body mass), and has no obvious toxic reaction, and has the basic requirements of drug formation.
【作者单位】： 山西医科大学公共卫生学院;广东省医学实验动物中心;广东省职业病防治院广东省职业病防治重点实验室;
【基金】：广东省科技计划项目(2016A030310319);广东省科技计划重大专项(2012A080201011) 国家重大新药创制科技重大专项入库课题(2015GKH-384) 佛山市科技计划项目(2012HY100302)
【分类号】：R135.1
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