L-精氨酸对内毒素诱导大鼠肺组织线粒体损伤的影响

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LPS 5 mg/kg(用生理盐水稀释至1 ml/kg),S组给予生理盐水1 ml/kg,3 h后L-Arg组腹腔注射L-Arg 500 mg/kg(用生理盐水稀释至1 ml/kg),S组和Au组给予生理盐水1 ml/kg.注射L-Arg或生理盐水后3 h.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-Ars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.

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

Objective To evaluate the effects of L-aronine(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):groupⅠsham operation(S);group ⅡLPS and group Ⅲ LPS+L-Arg.LPS 5 mg/kg in normal saline(NS)1 ml/kg waft given iv in group Ⅱ and Ⅲ while in group Ⅰ NS 1 ml/kg was given iv instead of LPS. L-Arg 500 ms/kg in NS 1 ml/kg was given intrapefitoneally(IP)at 3 h after LPS administration in group Ⅲ,while in group Ⅰ I and Ⅱ NS1 ml/kg was injected IP instead of L-Arg.The animals were sacrificed at 3 h after L-Arg injection by exsanguination and the lungs were immediately removed.The mitochondrias of the lungs were isolated by differentia 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,mitocho-ndrial activity and membrBne fluidity of mitochondria wefe measured.Ultrastructure of cells in lung was examined wlth eleciron microscope.Results The SOD,GSH-Px.ATPase and mitochondriai activities and the membrane fluidity of mitochondria were significantly decreased,while the MDA and NO contents and iNOS,NOS activities and the degree of mitochondriM swelling in the lung were significantly increased in group LPS as compared with group S.The lung cytoplasm and mitoehondria swelled,the cfistae 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 mitochondrinl injury induced by LPS by enhancing antioxidative effects.