金属硫蛋白治疗硫酸镍致肾脏损伤的实验研究

目的 探讨金属硫蛋白（MT）对硫酸镍致小鼠肾脏损伤的治疗效果及作用机制. 方法 60只清洁级昆明（KM）种小鼠,雌雄各半,随机分为5组：对照组,硫酸镍（Ni＋2）染毒组,低、中、高剂量MT治疗组.对照组灌胃生理盐水,镍染毒组灌胃2.5 mg/kg·bw硫酸镍溶液;MT治疗组在给予Ni＋2染毒后再分别按5.0、10.0、20.0 mg/kg· bw剂量灌胃MT.各组灌胃时间均为15 d,每日一次;灌胃体积均为0.1 ml/10 g·bw.实验结束麻醉处死动物采血,取双肾脏作病理学检测;全自动生化分析仪检测血清BUN和CRE含量;试剂盒检测肾组织SOD活性和MDA含量. 结果 与对照组比较,镍染毒小鼠血清BUN和CRE增高、肾组织SOD活力下降、MDA含量增高（P＜0.05）.MT治疗后与镍染毒组比较小鼠血清BUN和CRE降低,SOD活力升高、MDA含量下降（P＜0.05）;MT治疗后肾病理损伤明显减轻,细胞管形消失,核坏死、出血等病变明显改善,其中以高剂量MT治疗肾损伤效果更佳. 结论 金属硫蛋白对镍致小鼠肾损伤有治疗作用,其机制与抗氧化损伤有关.

Experimental Study on the Treatment of Kidney Injury Induced by Nickel Sulfate by Metallothionein

Objective To investigate the treatment effect and mechanism of metallothionein （MT） on kidney injury induced by nickel sulfate in mice.Methods Thirty male and thirty female Kunming mice of clean grade were randomly divided into 5 groups：control group,Ni＋2-exposed group,low dose MT protection group,middle dose MT protection group and high dose MT protection group.The mice in the control group were intragastrically administered with saline.The mice in the Ni＋2-exposed group were intragastrically administered with 2.5rmg/kg· bw nickel sulfate in solution.The mice in the three MT protection groups were simultaneously intragastrically administered with MT at the dose of 5.0,10.0 and 20.0mg/kg· bw respectively after exposure to nickel sulfate.All of the mice were treated once a day for 15 days and with a gastric volume of 0.1ml/10g·bw.At the end of the experiment,the mice were sacrificed after anesthesia,and blood and kidneys were collected.Serum BUN and CRE levels were detected by automatic biochemical analyzer,and SOD activity and MDA contents in the kidney were measured by kits.The kidneys were examined pathologically.Results Compared with control group,serum BUN and CRE,and MDA content in the kidney significantly increased in the Ni＋2-exposed group,while the SOD activity in the kidney was decreased （P ＜0.05）.MT treatment in the MT protection groups reversed the changes,with decreased serum BUN,CRE and increased SOD activity and reduced MDA content in the kidney （P ＜ 0.05）.MT also significantly reduced the renal pathological injuries in that cellular casts disappeared and the pathokogical changes like nuclear necrosis and hemorrhage improved greatly.High dose MT has the best treatment effect on kidney injury.Conclusions Metallothionein has treatment effect on renal injury induced by nickel in mice,and its mechanism is associated with anti-oxidative damage.