吸入一氧化氮对内毒素性肺损伤大鼠肺磷脂合成的影响  

Effects of inhaled nitric oxide on denovo synthesis of phosphatidylcholine in adult rat lungs with endotoxin-induced inflammatory injury

作　　者：龚小慧[1] 胡肖伟[1] 孙波[1] 

机构地区：[1]复旦大学附属儿科医院呼吸急救实验室,上海200032

出　　处：《中华急诊医学杂志》2004年第6期382-385,共4页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金资助项目 ( 3 0 170 989)

摘　　要：目的　探讨吸入 2 0× 10 - 6 (V /V )浓度一氧化氮 (NO)气体对大鼠内毒素性肺炎症损伤时磷脂酰胆碱 (PC)合成代谢的影响。方法　成年大鼠先随机分为接受静脉注射内毒素 (LPS)和对照组(C) ,2 4h后再随机给予吸空气 (Air)、 95 %氧气 (O2 )、 2 0× 10 - 6 NO加空气 (NO)、 2 0× 10 - 6 NO加 95 %氧气 (O2 NO)干预。采用氚标记氯化胆碱掺入法 ,测大鼠合成PC能力。Weinhold法测肺组织磷酸胆碱二胞苷酰基转移酶 (CCT)的活性。结果　在干预后 4h ,NO组LPS大鼠肺组织 (LT)及支气管肺泡灌洗液(BALF)中总磷脂 (TPL)及饱和磷脂酰胆碱 (DSPC)放射活性小于其他各组 (P <0 0 1) ,CCT活性小于其他各组 (P <0 0 1)。在干预后 2 4h ,O2 组LPS大鼠LT及BALF中TPL及DSPC放射活性小于其他各组 (P <0 0 1) ,CCT活性、BALF中TPL含量、DSPC/TP均显著低于其他干预下的LPS大鼠 (P <0 0 1及P <0 0 5 )。结论　针对炎症损伤肺 ,吸入 2 0× 10 - 6 浓度的NO 2 4h不会对磷脂酰胆碱合成代谢产生持续影响 ,并能拮抗高氧对磷脂合成的抑制作用。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 P<0.01 vs. all other subgroups), along with the lowest activity of CCT (751±57 pmol·min -1 mg -1 ), compared to all other subgroups (all P<0.01 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 P<0.05).However, SRA levels in all LPS subgroups were significantly lower than those in the corresponding C-subgroups (P<0.05).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 lu

关 键 词：一氧化氮吸入 内毒素性肺损伤 大鼠 肺磷脂合成 磷酸胆碱二胞苷酰基转移酶活性 

分 类 号：R563[医药卫生—呼吸系统]