顺铂对LLC－PK_1细胞增殖的影响及硒的保护效应

Influence of Cisplatin on the Proliferation and DNA Synthesis in LLC-PK1 Cells and the Protective Effects of Selenium

本研究观察了顺铂（ＣＤＤＰ）对猪肾近曲小管上皮细胞（ＬＬＣ－ｐＫ＿１）增殖与ＤＮＡ合成代谢的影响以及亚硒酸钠与硒代蛋氨酸的保护作用。结果表明，ＣＤＤＰ对ＬＬＣ－ｐｋ＿１细胞具有明显的毒性作用，在５～１５０μｍｏｌ／Ｌ范围内，ＣＤＤＰ与ＬＬＣ－ｐＫ＿１细胞作用１２ｈ，对细胞增殖已呈明显的抑制作用，其ＩＣ＿（５０）为１０９．５μｍｏｌ／Ｌ；作用２４ｈ时，其抑制效应更加明显，并存在剂量效应关系。ＬＬＣ－ｐｋ＿１细胞ＤＮＡ合成代谢对ＣＤＤＰ更为敏感，作用３ｈ，ＤＮＡ合成就受到明显的抑制，其ＩＣ＿（５０）为１２０．５μｍｏｌ／Ｌ。ＣＤＤＰ与ＬＩＣ－Ｐｋ＿１细胞作用３ｈ，对ＲＮＡ及蛋白质合成也具有明显的抑制作用。Ｎａ２ＳｅＯ３与Ｄ，Ｌ－ＳｅＭｅｔ两种不同硒化合物，当硒与ＣＤＤＰ的浓度比为１：１０时，Ｎａ２ＳｅＯ３未显示对ＣＤＤＰ的ＤＮＡ合成抑制作用有何保护作用，而Ｄ，Ｌ－ＳｅＭｅｔ则在一定程度上能减轻ＣＤＤＰ对ＬＬＣ－ｐｋ＿１细胞ＤＮＡ合成的抑制作用，但Ｄ，Ｌ－ＳｅＭｅｔ提前或与ＣＤＤＰ同时加入，其保护作用没有明显差异。

LC-pK_1 the pig kidney cell line,was utilized in studying mechanisms of nephrotoxicity induced bycisdiamminedichloroplatium(CDDP)and the protective effect,of sodium selenite and selenomethionine.At doseof 5-150μmol/L CDDP,the cell viability of LLC-pK1 after a 6h of exposure Was not changed significantly.After12h exposure to CDDP a dose-dependent decrease in cell viability was observed with a I C_(50) value of 109.5μmol/L.The inhibition of DNA,RNA and protein was evident as early as 3h post treatment.The effect of sodiumslenite and selenomethionine on CPDP induced inhibition of the[3￣H thymidine in corporation was investigatedin LLC-pK_1 cells.Sodium selenite at 10μmol/L unchanged the inhibition of the DNA synthesis induced by CDDPat 100μmol/L when added to the culture inediurn either before or after the CDDP,however,the inhibition of DNA synthesis by CDDP was significantly decreaxed by similar additions of selenomethionine either before orafter the CDDP.It was suggested that sodium selenite and selenomethionine have different protecrive effectagainst CDDP-induced inhibition of DNA synthesis.