慢性和急性染镉所致小鼠肾损伤的比较

Comparison of the renal injury induced by chronic and acute cadmium exposure in mice

目的比较慢性和急性染镉所致肾损伤的差异。方法给小鼠多次注射ＣｄＣｌ２（剂量：镉０．８～１．２ｍｇ／ｋｇ，每周６次，共６周），或一次给予大量注射镉金属硫蛋白复合物（ＣｄＭＴ，剂量：镉０．２～０．４ｍｇ／ｋｇ），然后比较其肾损伤。结果小鼠一次性大量注射ＣｄＭＴ主要产生肾脏近曲小管的坏死，虽然其肾镉含量仅为８μｇ／ｇ，但尿蛋白、尿糖、尿酶活力和血尿素氮含量均明显增高。与此相比，慢性染镉的小鼠肾镉含量高达１３５μｇ／ｇ，但仅有轻度近曲小管坏死及浊肿，上述尿、血指标仅略为增高。除近曲小管损伤外，慢性染镉还造成小鼠肾小球损伤，间质炎症，肾小管细胞凋亡、萎缩及再生。小鼠ＣｄＭＴ在慢性染镉后升高１００倍，达４５０μｇ／ｇ，但急性染镉仅略升高到２５μｇ／ｇ。结论用注射ＣｄＭＴ的急性染镉法来研究慢性染镉所致的肾损伤有一定的局限性。

In order to study the difference of renal injury between chronic and acute cadmium exposure,mice were given daily sc injections of CdCl2(0.8￣1.2 mg Cd/kg,six times a week,for 6 weeks),or a single ip injection of cadmiummetallothionein complex(CdMT,0.2￣0.4 mg Cd/kg) to induce renal injury.Multiple injections of CdCl2 resulted in renal Cd load of 135 μg/g,along with a 100fold increase in renal MT.By contrast,renal Cd load in acute CdMTtreated mice was only 8 μg/g,with a mild induction of MT(5fold).In spite of lower Cd in kidneys,acute CdMT produced severe tubular necrosis,with remarkable proteinuria,glucosuria,enzymuria and elevated blood urea nitrogen.However,chronic CdCl2 produced tubular cell apoptosis as a feature of the lesion,and renal injury was mild.Besides,glomerular lesions and interstitial nephritis were also apparent following chronic CdCl2 administration.These results suggest that acute CdMT injection may not be an appropriate model to study chronic Cd nephropathy.