二巯基丙磺酸钠对小鼠汞中毒不同器官驱汞疗效的差异

Study on the difference of curative effect of conventional mercury displacement treatment on mercury in brain and kidney

目的探寻二巯基丙磺酸钠(DMPS)对汞中毒不同脏器汞的驱排效应及谷胱甘肽(GSH)抗氧化联合治疗对汞中毒的治疗作用。方法于2019年2月,将SPF级雄性SD大鼠50只随机分成5组:生理盐水阴性对照组(A组)、氯化汞阳性对照组(B组)、治疗组(C组:肌肉注射DMPS 15 mg/kg、D组:肌肉注射DMPS 30 mg/kg、E:肌肉注射DMPS 15 mg/kg,同时腹腔注射GSH 200 mg/kg),每组10只大鼠。B、C、D、E组大鼠皮下注射氯化汞溶液(1 mg/kg)建立亚急性汞中毒肾脏损伤大鼠模型,A组大鼠皮下注射生理盐水。模型建立后,留取尿液,各治疗组大鼠按分组浓度分别注射DMPS、GSH,A和B组大鼠注射生理盐水,于染毒后21 d(治疗7 d)、28 d(治疗14 d)时分别收集每组5只大鼠的尿样和血样,检测血生化、尿汞、尿微量白蛋白及肾皮质、大脑皮层和小脑中汞含量及病理观察。结果汞染毒后B、C、D、E组大鼠肾皮质、大脑皮层、小脑汞含量升高,尿微量白蛋白升高,病理显示肾小管损伤、肾间质炎症。与B组比较,C、D、E组DMPS治疗后尿汞、肾皮质汞含量快速下降(P<0.05),大鼠小脑及大脑皮层汞水平无明显下降,但伴有尿微量白蛋白DMPS治疗后一过性增高(P<0.05);E组联合GSH治疗后肾间质炎症好转。尿汞与肾皮质、大脑皮层、小脑汞含量之间均呈正相关(r=0.61、0.47、0.48,P<0.05)。结论DMPS驱汞治疗可明显降低肾脏金属汞水平,脑皮质和小脑的金属汞水平无明显变化。

Objective To explore the expulsion effect of sodium dimercaptopropanesulfonate(DMPS)on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione(GSH)combined with antioxidant therapy on mercury poisoning.Methods In February 2019,50 SPF male SD rats were randomly divided into 5 groups,10 rats in each group:A(saline negative control group),B(HgCL2 positive control group),treatment group(C:intramuscular injection of DMPS 15 mg/kg treatment,D:intramuscular injection of DMPS30 mg/kg treatment,E:intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment).Rats in group B,C,D and E were subcutaneously injected with mercury chloride solution(1 mg/kg)to establish a rat model of subacute mercury poisoning kidney injury.Rats in group A were subcutaneously injected with normal saline.After the establishment of the model,rats in the treatment group were injected with DMPS and GSH.Rats in group A and group B were injected with normal saline.At 21 d(treatment 7 d)and 28 d(treatment 14 d)after exposure,urine and blood samples of 5 rats in each group were collected.Blood biochemistry,urine mercury,urine microalbumin and mercury content in renal cortex,cerebral cortex and cerebellum were detected.Results After exposure to mercury,the contents of mercury in renal cortex,cerebrum and cerebellum of rats in group B,C,D and E increased,and urine microalbumin increased.Pathology showed renal tubular injury and renal interstitial inflammation.Compared with group B,urinary mercury and renal cortex mercury in group C,D and E decreased rapidly after DMPS treatment,and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats,accompanied by transient increase in urinary albumin after DMPS treatment(P<0.05);the renal interstitial inflammation in group E was improved after GSH treatment.There was a positive correlation between urinary mercury and the contents of mercury in renal cortex,cerebral cortex and cerebellum(r=0.61,0.47,0.48,P<0.05).Conclusion DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney,and there is no significant change in the level of metal mercury in the cortex and cerebellum.