硝酸铋与丙磺舒合用对顺铂肾毒性的防护作用

Protective effect of coadministration of bismuth nitrate and probenecid on cisplatin induced nephrotoxicity

毒性剂量的顺铂（ＣＰ３０μｍｏｌ·ｋｇ－１ｉｐ）可引起血尿素氮（ＢＵＮ）升高。硝酸铋（ＢＮ）５μｍｏｌ·ｋｇ－１于ＣＰ前４８和２４ｈｓｅ，丙磺舒（Ｐｒｏ）７００μｍｏｌ·ｋｇ－１于ＣＰ前１５，１ｈ及ＣＰ后５ｈｉｇ，或ＢＮ与Ｐｒｏ二者半量合用，按上述给药，均能抑制ＣＰ引起的ＢＵＮ升高，尤以ＢＮ＋Ｐｒｏ组抑制作用显著。肾脏光镜和电镜标本显示，ＣＰ使肾小管受损严重；ＢＮ组，Ｐｒｏ组和ＢＮ＋Ｐｒｏ组均使ＣＰ引起的肾小管受损减轻，尤以ＢＮ＋Ｐｒｏ组减轻明显。ＢＮ２．５－２０μｍｏｌ·ｋｇ－１剂量依赖性地诱导小鼠肾脏金属硫蛋白合成。Ｐｒｏ可使ＣＰ后２４ｂ肾铂含量明显降低；Ｐｒｏ或Ｐｒｏ＋ＢＮ使尿铂累积排出量增加，血浆铂浓度降低。提示ＰＦＯ防护ＣＰ肾毒性与其减少肾铂分布，增加尿铂排出有关。

The nepbrotoxicity induced by toxicdose of cisplatin (cis-diamminedichloroplatinum,CP)30μmol·kg-1 ip,characterized by high level of bloodurea nitrogen,was significantly attenuated bypretreatment with bismuth nitrate(BN)5 μmol·kg-1 sc,48 and 24 h prior to CP,or probenecid(Pro)700 μmol·kg-1 ig,15 and 1 h prior to and 5 h afterCP. or half dose of BN and Pro in combination(P<0.05-0.01),The combindtion of BN and Pro wasmost ehctive in reducing the CP-induced rise inblood urea nitrogen. Light and electron microscopic ex-aminations of the kidney demonstrated that severerenal injury appeared at the corticomedullary junctionafter treatment with CP alone. The renal tubules in themice treated with BN or Pro or a combination of halfdose of both drugs plus CP were relatively normal.Inthe present study renal metallothionein had increaseddose-dependently in mice pretreated with BN(r=0.989,P<0.05).Renal platinum content of micepretreated with Pro was significantlv lower than that inmice treated with CP alone,at 24 h after CP injection.Pro alone or coadministered with BN increased theurinary excretion of platinum significantly,and decreased plasma platinum significantly.