亚慢性镉中毒肾功能性损伤小鼠模型的研究

Experimental study on subchronic kidney functional damage mouse model caused by cadmium

目的建立小鼠亚慢性镉中毒肾功能性损伤模型,用于驱镉新药的研究。方法 24只雄性NIH小鼠随机分为正常对照组,低、中、高剂量组共4组,每组6只。低、中、高剂量组分别按1次/d,连续5 d总染毒剂量0.84,1.69,3.37 mg Cd/kg进行腹腔注射氯化镉和巯基乙醇混合溶液染毒,正常对照组注射生理盐水。染毒后观察35 d。以尿β2-微球蛋白和视黄醇结合蛋白含量、肾镉、肾脏病理检查为主要参考指标,选出合适的模型建立方案。结果高剂量组的尿β2-微球蛋白显著高于对照组(P<0.05),各染毒组的尿视黄醇结合蛋白含量与对照组相比差异无统计学意义(P>0.05),血镉和肾镉含量均显著高于正常对照组(P<0.05),各组动物的肾脏和睾丸均未发现明显病理改变。结论腹腔注射镉总剂量3.37 mg Cd/kg(1次/d,连续5 d),染毒后观察35 d可成功建立亚慢性镉中毒肾功能性损伤小鼠模型。

Objective To establish a kind of subchronic kidney functional damage mouse model for the study on a new cadmium chela- ting agent. Methods Twenty-four male NIH mice were divided randomly into 4 groups （n = 6 in each group） ： control group, low, middle and high dose groups. Mice in low, middle and high dose groups were intraperitoneally injected with cadmium chloride solution containing mercaptoethanol at the total dose of 0. 84,1. 69 ,3. 37 mg Cd/kg respectively （ once a day for 5 d）, while mice were injected with physiological saline in control group. After the last injection, mice were all observed for 35 d. The renal Cd, urinary 62-microglobu- hn（UBMG） ,urinary retinol-binding protein（URBP） and renal pathological sections were observed to find out a suitable way to estab- lish the renal functional damage animal model. Results UBMG in high dose group was significantly higher than that in control group （P 〈 0.05 ）. URBP in low, middle and high dose groups were comparable with that in control group （P 〉 0.05 ）. Blood cadmium and renal cadmium in low,middle and high dose groups were higher than that in control group（P 〈 0.05）. No obvious pathological changes in kidneys and testes of all mice were found. Conclusion The subchronic renal functional damage mouse model could be successfully established 35 d after the last intraperitoneal injection of cadmium at the total dose of 3.37 mg/kg （ once a day for 5 d）.