实验性肺纤维化大鼠肺泡巨噬细胞脂质过氧化先于其细胞因子的释放

Lipid peroxidation precedes TNF and PDGF release in alveolar macrophage of the experimental pulmonary fibrosis rats

目的 :动态观察博莱霉素 (BLM)致大鼠肺纤维化过程中肺泡巨噬细胞 (AM)脂质过氧化损伤和抗氧化损伤指标的变化 ,探讨与其释放肿瘤坏死因子 (TNF -α)和血小板源生长因子 (PDGF)的关系。方法 :分离AM测定其中丙二醛 (MDA)含量和谷胱甘肽过氧化物酶 (GSH -Px)活性 ;行体外AM纯培养 ,测定其培养上清中上述两种细胞因子含量。结果 :(1)AM中MDA第 1d即明显升高 ,第 3d至高峰 ,急性期过后则逐渐降至正常 ;而GSH -Px则早期处于极低状态 ,14d后逐渐恢复近于正常。 (2 )AM释放上述两种细胞因子于第 3d开始明显增高 ,并呈动态变化。 (3)AM脂质过氧化损伤先于其释放TNF -α和PDGF。结论

AIM: To evaluate the role of alveolar macrophage(AM)lipid peroxidation in bleomycin(BLM)-induced TNF-α and PDGF release from AM in rats. METHODS: Male SD rats were intratracheally instilled with saline or BLM(5 mg/kg body weight), and AM were isolated and analyzed for malondialdehyde (MDA) and glutathione peroxidase(GSH-Px) following 1,3,7,14 or 28 day (s).Simultaneously, TNF-α and platelet-derived growth factor(PDGF) were also determined in AM-conditoned media by ELISA and bioassay respectively. RESULTS:(1) MDA in AM was markedly increased on day 1,peaked on day 3 and then decreased to near control level on day 7; on the other hand, GSH-Px activity in AM were decreased to non-detectable levels during day 1-7 after BLM instillation, returned to the control level by day 14. (2) TNF-α and PDGF were increased significantly from the third day on and then exhibited a consectutive changes.(3)AM lipid peroxidation preceded TNF-α and PDGF release. CONCLUSION: Prior oxidative changes leading to AM lipid peroxidation,depletion of antioxidative pool might be essential for the subsequent mediators release in BLM-induced pulmonary fibrosis.