L-精氨酸对内毒素诱导大鼠肺组织线粒体损伤的影响  

Effects of L-arginine on LPS-induced lung mitochondrial injury in rats

作　　者：张建新[1] 李兰芳[1] 尚涛[1] 

机构地区：[1]河北省医学科学院药物研究所,石家庄市050021

出　　处：《中华麻醉学杂志》2009年第3期250-253,共4页Chinese Journal of Anesthesiology

基　　金：国家人事部留学人员重点资助项目（9900789）;河北省博士基金资助项目（99547015D）

摘　　要：目的评价L-精氨酸（L-Arg）对内毒素（LPS）诱导大鼠肺组织线粒体损伤的影响，探讨其减轻内毒素性急性肺损伤的作用机制。方法雄性SD大鼠24只，随机分为3组（n=8）：假手术组（S组）、LPS组和L-Arg组。LPS组和L-Arg组静脉注射LPS5mg／kg（用生理盐水稀释至1ml／kg），S组给予生理盐水1ml／kg，5h后L-Arg组腹腔注射L-Arg500mg／kg（用生理盐水稀释至1ml／kg），S组和ALI组给予生理盐水1ml／kg。注射L-Arg或生理盐水后3h，取肺组织，提取线粒体，测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH．Px）、ATPase、丙二醛（MDA）、一氧化氮合酶（NOS）、诱生型一氧化氮合酶（iNOS）、结构型一氧化氮合酶（cNOS）、一氧化氮（NO）的水平、线粒体膜肿胀度、线粒体活力和线粒体膜流动性；电镜观察肺组织超微结构。结果与S组比较，LPS组SOD、GSH．Px、ATPase、线粒体活力和线粒体膜流动性降低，MDA、NOS、iNOS、NO及线粒体膜肿胀度升高（P〈0．01）；与LPS组比较，L-Arg组SOD、GSH-Px、ATPase、线粒体活力和线粒体膜流动性升高，MDA含量和线粒体膜肿胀度降低（P〈0．05）。L-Arg组细胞肿胀、线粒体肿胀和空泡化的程度轻于LPS组。结论L-Arg可减轻LPS诱导大鼠肺组织线粒体损伤，其机制与增强抗过氧化能力有关。Objective To evaluate the effects of L-arginine （L-Arg） on LPS-induced lung mitochondrial injury in rats. Methods Twenty-four male SD rats weighing 230-270 g were randomly divided into 3 groups （ n = 8 each） ： group Ⅰ sham operation （S） ; group Ⅱ LPS and group Ⅲ LPS ＋ L-Arg. LPS 5 mg/kg in normal saline （NS） 1 ml/kg was given iv in groupⅡ and Ⅲ while in group Ⅰ NS 1 ml/kg was given iv instead of LPS. L-Arg 500 mg/kg in NS 1 ml/kg was given intraperitoneally （IP） at 3 h after LPS administration in group Ⅲ , while in group Ⅰ and Ⅱ NS 1 ml/kg was injected IP instead of L-Arg. The animals were sacrificed at 3 h after L-Arg injection by exsauguination and the lungs were immediately removed. The mitochondrias of the lungs were isolated by differential centrifugation. The activities of SOD, GSH-Px, ATPase, inducible, constitutive and total nitric oxide synthase （iNOS, cNOS, NOS） and MDA and NO contents, the degree of mitochondrial swelling, mitochondrial activity and membrane fluidity of mitochondria were measured. Ultrastructure of cells in lung was examined with electron microscope. Results The SOD, GSH-Px, ATPase and mitochondrial activities and the membrane fluidity of mitochondria were significantly decreased, while the MDA and NO contents and iNOS, NOS activities and the degree of mitochondrial swelling in the lung were significantly increased in group LPS as compared with group S. The lung cytoplasm and mitochondria swelled, the cristae were disrupted, dissolved or disappeared in LPS group （ Ⅱ ） . The LPS-induced changes were ameliorated by L-Arg in group Ⅲ as compared with group Ⅱ. Conclusion L-Arg can attenuate lung mitochondrial injury induced by LPS by enhancing antioxidative effects.

关 键 词：精氨酸 内毒素血症 肺 线粒体 

分 类 号：R285.5[医药卫生—中药学] R135.2[医药卫生—中医学]