本文選題：N-( + -五羥基己基)-(N-二取代甲酸鈉基)-L-甲硫氨酸鈉��； 參考：《中國職業(yè)醫(yī)學》2017年02期

【摘要】：目的探討靜脈滴注驅(qū)鎘劑N-(2,3,4,5,6-五羥基己基)-(N-二取代甲酸鈉基)-L-甲硫氨酸鈉(GMDTC)不同劑量下的驅(qū)鎘效果。方法雄性新西蘭兔隨機分為空白對照組、GMDTC高劑量對照組、模型對照組、依地酸鈉鈣(EDTA)對照組和GMDTC低、中、高劑量組,每組5只。空白對照組和GMDTC高劑量對照組新西蘭兔分別經(jīng)耳緣靜脈予0.90%氯化鈉注射液,模型對照組、EDTA對照組和3個GMDTC劑量組新西蘭兔分別經(jīng)耳緣靜脈予濃度為2μmol/kg氯化鎘及濃度為40μmol/kg的β-巰基乙醇的混合溶液,給藥量為5.0 mL/kg體質(zhì)量,1次/d,連續(xù)5 d。于造模第41天即治療第1天,空白對照組和模型對照組新西蘭兔均經(jīng)耳緣靜脈予0.90%氯化鈉注射液250 mL,EDTA對照組新西蘭兔予劑量為93.5 mg/kg體質(zhì)量的EDTA溶液,GMDTC高劑量對照組和3個GMDTC劑量組新西蘭兔分別予劑量為108.0、12.0、36.0、108.0 mg/kg體質(zhì)量的GMDTC溶液,1次/d,6次/周,連續(xù)4周。檢測各組新西蘭兔治療前后尿β_2-微球蛋白(β_2-MG)、腎鎘、血鎘和尿鎘水平。結(jié)果實驗期間,新西蘭兔體質(zhì)量隨飼養(yǎng)時間的增加而增加(P0.01)。模型對照組、EDTA對照組和3個GMDTC劑量組新西蘭兔治療前尿β_2-MG水平均高于空白對照組(P0.05)。GMDTC中、高劑量組新西蘭兔治療后腎鎘水平均低于模型對照組和EDTA對照組(P0.05)。EDTA對照組和3個GMDTC劑量組新西蘭兔治療后的血鎘水平均低于同組治療前(P0.05),且均低于治療后的模型對照組(P0.05);GMDTC中、高劑量組和EDTA對照組新西蘭兔治療后血鎘水平兩兩比較,差異均無統(tǒng)計學意義(P0.05)。治療后各時間點(治療后第1、6、8、13、15、20、22和28天)的新西蘭兔尿鎘水平,在EDTA對照組和3個GMDTC劑量組均低于同時間點模型對照組(P0.05);治療后除第20和22天外,其余6個時間點新西蘭兔尿鎘水平均隨GMDTC劑量的增加而增加(P0.05)。GMDTC低、中、高劑量組新西蘭兔治療后血鎘驅(qū)除率分別為70.06%、74.86%和78.05%,腎鎘驅(qū)除率分別為14.27%、27.95%和61.24%。結(jié)論 GMDTC靜脈滴注劑量為108.0 mg/kg體質(zhì)量對鎘中毒兔模型(相當于人用劑量36.0 mg/kg體質(zhì)量)的驅(qū)鎘效果顯著,未見明顯毒性反應(yīng),具備成藥性基本要求。
[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.
【作者單位】： 山西醫(yī)科大學公共衛(wèi)生學院;廣東省醫(yī)學實驗動物中心;廣東省職業(yè)病防治院廣東省職業(yè)病防治重點實驗室;
【基金】：廣東省科技計劃項目(2016A030310319);廣東省科技計劃重大專項(2012A080201011) 國家重大新藥創(chuàng)制科技重大專項入庫課題(2015GKH-384) 佛山市科技計劃項目(2012HY100302)
【分類號】：R135.1
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本文編號：2021460