过氧亚硝基阴离子对气道上皮细胞的损伤作用

目的:探讨过氧亚硝基阴离子(ONOO^-)对气道上皮细胞的损伤作用。方法:在培养的大鼠气道上皮(RTE)细胞观察外源性给予ONOO^-对RTE细胞线粒体呼吸、8-羟基脱氧鸟苷(8-OHdG)水平、乳酸脱氢酶(LDH)释放及凋亡细胞百分率的影响。结果:ONOO^-(0.25-1mmol/L)呈剂量依赖方式抑制RTE细胞线粒体呼吸功能、增高LDH释放率。并呈剂量依赖性引起8-OHdG水平升高。不同浓度(0.25mmol/L、0.5mmol/L及1mmol/L)ONOO^-均以时间依赖方式引起RTE细胞凋亡。结论:ONOO^-可引起培养的RTE细胞发生凋亡和坏死。低浓度的ONOO^-损伤RTE细胞以凋亡为主;高浓度的ONOO^-可能主要引起RTE细胞发生坏死。ONOO^-对RTE细胞线粒体呼吸抑制和DNA的氧化损伤可能是ONOO^-导致RTE细胞坏死和凋亡的主要原因。

Airway epithelial injuryinduced by peroxynitrite

AIM:To study the effect of ONOO- on the airway epithelial injury. METHODS: The mitochondrial respiration, the amount of lactate dedydrogenase (LDH) release into the cell culture medium, the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the cellular apoptosis were examined after exposure of cultured rat tracheal epithelial (RTE) cells to ONOO-. RESULTS: Exposure of RTE cells to 0.25, 0.5 and 1 mmol/L ONOO- caused a dose-dependent suppression of the mitochondrial respiration . ONOO- also caused a dose-dependent increase in the percentage of LDH release. Exposure of RTE cells to ONOO- resulted in an increased generation of 8-OHdG in a dose-dependent manner. ONOO- caused an increase in apoptotic percentage in RTE cells in a time-dependent manner at different concentrations. CONCLUSION: ONOO- could cause necrosis and apoptosis in cultured RTE cells. Low concentration of ONOO- caused apoptosis in a time-dependent manner. Whereas exposure to high concentration of ONOO- resulted in cell necrosis, ONOO- caused a dose-dependent increase in the percentage of LDH release. Suppression of mitochondrial respiration and oxidative DNA damage by ONOO- may be the major cause of cellular injury induced by ONOO-.