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目的探讨一氧化氮（ＮＯ）参与铁负荷肾小管细胞毒作用的可能机制，评价氧自由基清除剂在铁肾小管细胞毒中的防治作用及其与ＮＯ的关系。方法在建立原代鼠肾近端小管上皮细胞培养体系的基础上，以孵育液中ＮＯ２－产量（Ｇｒｉｅｓｓ反应）和小管细胞乳酸脱氢酶（ＬＤＨ）释放率改变为线索，比较不同剂量铁剂、各氧自由基清除剂、Ｌ－精氨酸（Ｌ－Ａｒｇ）和ＣＯ合成酶抑制剂，左旋硝基精氨酸甲酯（Ｌ－ＮＡＭＥ）分别作用 １２ ｈ后在非脂多糖（ＬＰＳ）组和 ＬＰＳ组（１０ ｕｇ／ｍｌ）中对小管细胞毒作用及与ＮＯ代谢的影响；同时用半定量逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）法检测不同剂量铁剂与ＬＰＳ的联用下诱导型一氧化氮合酶（ｉＮＯＳ）ｍＲＮＡ的表达改变。结果ＮＴＡ－Ｆｅ可以剂量依赖的方式同步增加ＬＤＨ释放（Ｐ＜０．００１）及孵育液中Ｎ０２－的产量（Ｐ＜０．００１）；但在ＬＰＳ组中细胞毒作用的增加（Ｐ ＜０．００１）并不伴随Ｎ０２－的明显改变（Ｐ＞０．０５）。ＬＰＳ诱导的ｉＮＯＳ转录上调可为ＮＴＡ－Ｆｅ增强，但仅限于５００ｕｍｏｌ／Ｌ（Ｐ＜０．０１）。在ＬＰＳ组中，加入Ｌ－精氨酸及不同剂量Ｌ－ＮＡＭＥ可分别加重和缓解铁的细胞毒作用；然而，Ｌ－ＮＡＭＥ
Objective To investigate the possible mechanism of nitric oxide (NO) involved in the renal tubular cytotoxicity induced by iron overload and to evaluate the preventive and therapeutic effects of oxygen free radical scavenger on renal tubular cell toxicity and its relationship with NO. Methods Based on the establishment of a culture system of primary rat renal proximal tubule epithelial cells, the changes of NO2-production (Griess reaction) and LDH release rate in the culture fluid were used as clues to compare the effects of different doses of iron , L-arginine (L-Arg), CO synthase inhibitor and L-NAME were treated with LPS for 12 h, respectively. Group and LPS group (10 ug / ml) on the cytotoxicity of tubules and NO metabolism; at the same time, the combination of different doses of iron and LPS was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) Under-inducible nitric oxide synthase (iNOS) mRNA expression changes. Results NTA-Fe could increase the release of LDH (P <0.001) and the production of N02- in the incubation solution in a dose-dependent manner (P <0.001), but increased the cytotoxicity in the LPS group (P <0 .001) was not associated with a significant change in N02- (P> 0.05). LPS-induced iNOS transcription up-regulation could be enhanced NTA-Fe, but only 500umol / L (P <0.01). In the LPS group, L-arginine and different doses of L-NAME increased and alleviated the cytotoxicity of iron, respectively; however, L-NAME