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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(P<0.01)。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(P<0.05)。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(P<0.05)。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(P<0.05),且均低于治疗后的模型对照组(P<0.05);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(P>0.05)。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(P<0.05);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(P<0.05)。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。
OBJECTIVE: To investigate the effects of cadmium dithiocarbamate (CdD) on the proliferation of different doses of N- (2,3,4,5,6-pentahydroxyhexyl) - (N-disubstituted sodium formate) -L-methionine Cadmium effect. Methods Male New Zealand white rabbits were randomly divided into blank control group, GMDTC high dose control group, model control group, EDTA sodium EDTA group and GMDTC low, medium and high dose groups. The rabbits in the blank control group and the GMDTC high dose control group were given 0.90% sodium chloride injection through the ear vein respectively. The model control group, the EDTA control group and the three GMDTC dose groups were administered New Zealand rabbits via the ear vein with a concentration of 2μmol / kg cadmium chloride and the concentration of 40μmol / kg of β-mercaptoethanol mixed solution, the dose of 5.0 mL / kg body weight, 1 time / d, continuous 5 d. On the 41 st day of treatment, on the first day of treatment, New Zealand rabbits in the blank control group and the model control group were given 250 mL of 0.90% sodium chloride injection through the ear veins, and the New Zealand rabbit dose of EDTA control group was 93.5 mg / kg body Quality EDTA solution, GMDTC high dose control group and three GMDTC dose groups New Zealand rabbits were given a dose of GMDTC solution of 108.0,12.0,36.0,108.0 mg / kg body weight, once / d, 6 times / week, continuous 4 week. The levels of urinary β_2-microglobulin (β_2-MG), renal cadmium, serum cadmium and urinary cadmium in New Zealand rabbits before and after treatment were measured. Results During the experiment, the body weight of New Zealand rabbits increased with feeding time (P <0.01). The levels of urinary β_2-MG before treatment in model control group, EDTA control group and three GMDTC dose groups were higher than those in blank control group (P <0.05). The levels of renal cadmium in GMDTC middle and high dose New Zealand rabbits after treatment were lower than those in model control group and EDTA control group (P <0.05). The levels of serum cadmium in the EDTA control group and the three GMDTC groups were lower than those in the control group (P <0.05), and were lower than those in the model control group (P <0.05) There was no significant difference in blood cadmium levels between the dose group and the EDTA control group after New Zealand rabbit treatment (P> 0.05). Urinary cadmium levels in New Zealand rabbits at each time point after treatment (1st, 6th, 8th, 13th, 15th, 20th, 22th and 28th day after treatment) were lower than those in the EDTA control group and the three GMDTC dose groups (P <0.05). Urinary cadmium levels in New Zealand rabbits increased with the increase of GMDTC dose (P <0.05) except the 20th and 22nd days after the treatment. The serum levels of cadmium were 70.06%, 74.86% and 78.05% in the GMDTC low, medium and high doses of New Zealand rabbits respectively. The urinary Cd removal rates were 14.27%, 27.95% and 61.24% respectively. Conclusion The dose-effect of GMDTC at 108.0 mg / kg body weight in cadmium poisoning rabbit model (equivalent to a human dose of 36.0 mg / kg body weight) has a significant cadmium repellent effect with no obvious toxic reaction and possesses the basic requirements of drug-induced.