过氧亚硝基阴离子对气道上皮细胞的损伤作用

Airway epithelial injury induced by peroxynitrite

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 2 5 - 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 2 5mmol/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。

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 -. [