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《Journal of Emergency Medicine》 2004-06
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Effects of inhaled nitric oxide on denovo synthesis of phosphatidylcholine in adult rat lungs with endotoxin-induced inflammatory injury

GONG Xiaohui, HU Xiaowei, SUN Bo. Laboratory of Pediatric Respiratory and critical Care Medicine, Children's Hospital of Fudan University, Shanghai 200032, China  
Abstract Objective To investigate whether hyperoxia and/or inhaled nitric oxide (iNO) may affect de novo synthesis of phosphatidylcholine (PC) in mature lungs with inflammatory injury.Methods Healthy adult rats were first assigned into a normal control group (C) or a group with lipopolysaccharides (2mg·kg -1 i.v) to induce inflammatory lung injury in 24 h (LPS), and then both groups were randomly allocated to 4 subgroups exposed for 4 h and 24 h, to: air, 95% oxygen (O 2+), air and 20×10 -6 (vol/vol) NO (NO), and 95% oxygen and 20×10 -6 NO (O 2NO). Synthesis of PC through de novo pathway was determined by incorporation rate of [Methyl- 3H]-choline (15μCi, i.v.) into PC, with reference to total phospholipid (TPL), desaturated PC (DSPC) and total proteins (TP) in either lung tissue (LT) or bronchoalveolar lavage fiuid (BALF). Activity of cytidine triphosphate: phosphocholine cytidylyltransferase (CCT) in LT was measured by incorporation rate of [methyl- 14 C] phosphocholine into cytidine 5'-diphosphocholine. Results At 4 h, the LPS-NO subgroup had lowest specific radioactivity of PC (SRA) in TPL and DSPC in both LT and BALF, respectively (all P0.01 vs. all other subgroups), along with the lowest activity of CCT (751±57 pmol·min -1 mg -1 ), compared to all other subgroups (all P0.01 vs. other subgroups). At 24 h, the LPS-O 2 had lower levels of SRA of TPL and DSPC in LT and BALF activity of CCT (604±58 pmol·min -1 ·mg -1 ) in LT and amount of TPL and DSPC/TP in BALF compared to those in the other LPS subgroups (P 0.01 or P0.05).However, SRA levels in all LPS subgroups were significantly lower than those in the corresponding C-subgroups (P0.05).Conclusion The de novo synthesis of PC was hampered by LPS in rat lungs in association with decreased CCT activity. While iNO alone transiently inhibited this pathway at 4 h, hyperoxia after 24 h significantly suppressed it, suggesting that iNO has no adverse effects on pulmonary surfactant synthesis, in the LPS-induced lung injury.
【Fund】: 国家自然科学基金资助项目 ( 3 0 170 989)
【CateGory Index】: R563
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