二巯基丁二酸治疗慢性中度铅中毒的实验研究

目的 探讨二巯基丁二酸(又名二巯琥珀酸,DMSA)治疗慢性中度铅中毒幼兔的驱铅效果.方法 24 只离乳(45 d)雄性健康新西兰幼兔,数字表法随机分为治疗组、阳性对照组和阴性对照组,每组8只,经消化道染铅(醋酸铅,每天5 mg/kg) 6周复制中度铅中毒动物模型,然后给予DMSA 驱铅治疗,第1周每天给DMSA 1050 mg/m2 体表面积,然后改为每天700 mg/m2 体表面积连续2周,停药3周,每周采集血液和尿液,12周后杀死并取海马、睾丸、心脏、肝脏、肾脏和脾脏.用原子吸收分光光谱仪测定血铅,电感耦合等离子体质谱仪测尿铅和组织脏器铅,光学显微镜(简称光镜)下观察组织脏器的组织结构.结果 与阳性对照组(PG)相比,DMSA 治疗组(TG)的幼兔展尿铅浓度增加显著,从治疗前的(40.97±1.77)μg/L 显著增加至达到峰值 (1246.96±157.91)μg/L,然后逐步减少,第1周两组相比差异有统计学意义(F=2934.35,P＜0.01),三组间相比较差异均具有统计学意义(P值均＜0.01);同时血铅水平(blood lead levels,BLLs)在用药后由治疗前的(429.63±10.82)μg/L,锐减到第3周停药时的(238.50±11.82)μg/L,停药后出现一过性反弹,然后再次降低;而PG的BLLs在同时期中呈现缓慢下降过程,到停药3周后为(149.88 4±11.39)μg/L,基本接近于TG的(135.50±7.09)μg/L.TG新西兰兔的组织脏器铅含量显著降低,体重增长明显加快,光镜下观察睾丸和肝脏的病理损伤有一定程度的改善.结论 DMSA 治疗慢性中度铅中毒幼兔,可以快速有效降低血铅和软组织铅,在短时间内减轻铅对组织脏器的毒性作用,使组织脏器的损伤随着机体铅负荷的降低而有所减轻,对铅毒性作用导致的生长发育落后有一定的改善作用.

Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning

Objective To explore the effect of chelation therapy with suceimer (DMSA) in male rabbits of moderate lead poisoning during iuvenile stage.Methotis Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group,TG;positive control group,PG and for 6 weeks.Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks.while the other two groups weren't.Blood and urinary samples of all rabbits were collected per week.The tissues and organs of all rabbits were collected after 12 weeks.The blood lead levels (BLLs) were determined by atomic absorption spectrometer.The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry.Histopathology of tissue and organ was observed by light microscope.Resuits Compared with PG,the lead level in the morning urine of TG with DMSA chelating was increased significantly.The level was peaked at (1246.96±157.91)μg/L on the first day after chelating.While the base line was (40.97±1.77)μg/L before chelating.Meanwhile,the BLLs were sharply declined from (429.63±10.82)μg/L to (238.50±11.82)μg/L.The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation.The urine lead levels of these two groups were significantly different (F=2934.35,P＜0.01).Compared to each two groups in these three groups,there were significant difference(P＜0.01).The authors found the reversion of BLLs in first week after stop chelating.The BLLs of PG presented the slow course of declining in tlle same time,were(135.50±7.09)μg/L,very close to the level of TG for(149.88±11.39)μg/L Compared with treatment discontinuation for 3 weeks,the urine lead levels and the body weight gain of the therapy group increased more than that of PG,and the BLLs and the lcad concentrations in tissues and organs decreased more than that of PG,and histopathology in the liver tissues and testicle tissues were improved.Condusion DMSA ehelming for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively,decrease toxic effects of lead in a short period of time,thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden,and bring out improvement on the growth retardation caused by lead poisoning.