一氧化氮在急性肝衰竭中的作用

The Role of Nitric Oxide in Acute Hepatic Failure

为探讨ＮＯ在急性肝衰竭中的作用，采用Ｄ－ＧａｌＮ（８００ｍｇ／ｋｇ）和ＬＰＳ（８μｇ／鼠）腹腔注射复制大鼠急性肝衰竭模型，用氨胍（ＡＧ，１００ｍｇ·ｋｇ－１·ｄ－１）和左旋精氨酸（ＬＡ，４００ｍｇ·ｋｇ－１·ｄ－１）皮下注射３ｄ，分别抑制和促进ＮＯ的合成，注射Ｄ－ＧａｌＮ和ＬＰＳ后２４ｈ处死，留血清测定ＮＯ、ＡＬＴ和ＡＳＴ的水平，肝组织测定诱导型ＮＯ合酶（ｉＮＯＳ）的活性并作组织学观察。结果发现急性肝衰竭时ＮＯ和ｉＮＯＳ的水平升高（Ｐ＜００５），与ＡＬＴ和ＡＳＴ的升高相一致（Ｐ＜００５），抑制ｉＮＯＳ的活性或促进ＮＯ的合成，则ＮＯ、ＡＬＴ和ＡＳＴ的水平降低（Ｐ＜００５）或升高（Ｐ＜００５），组织学观察证实了上述结果。说明ＮＯ及ｉＮＯＳ参与急性肝衰竭，抑制ＮＯ的合成对急性肝衰竭有保护作用。

The role of NO in the pathogenesis of acute liver failure was evaluated.Male wistar rats were subcutaneously injected with aminoguanidine (AG,100mg·kg -1 ·d -1 )and L-arginine (LA,400mg·kg -1 ·d -1 ) respectively,for 3 days,then D-galactosamine (D-GalN,800mg·kg -1 ·d -1 ) and LPS(8μg/rat) were intraperitoneally injected,it induced an acute hepatic failure.After 24 hours,the animals were executed,their plasma samples were harvested for the measurements of NO,ALT and AST.Meanwhile,their livers were excised for the assays of tissue inducible NO synthase(iNOS),and microscopical examination.The results showed that in the development of acute liver failure,the plasma levels of NO,iNOS,ALT and AST in exeperimental rats were significantly elevated than that of the controls( P <0 05),when pretreated with AG,those levels were significantly reduced including the activity of iNOS.However,pretreated with LA,those were obviously increased,except the activity of iNOS.These suggest that the NO and iNOS participated in development of acute hepatic failure,it was identified also by histopathological observation.Therefore,the inhibition of AG on iNOS has shown a protective effect,while the increase of NO synthesis induced by LA play a deteriorative action for hepatic function.