重型肝炎患者外周血内皮素及一氧化氮水平变化的意义

Clinical significance of changes of endothelin and nitric oxide levels in peripheral blood of patients with severe hepatitis

目的探讨内皮素（ＥＴ）和一氧化氮（ＮＯ）在重型肝炎（ＳＨ）发病中的作用．方法检测３０例ＳＨ，３２例慢性肝炎（ＣＨ）患者外周血ＥＴ和ＮＯ代谢物ＮＯ－２的水平，并用ＮＯ合成酶底物左旋精氨酸（ＬＡｒｇ）进行治疗前后对比．结果ＳＨ患者外周血ＥＴ和ＮＯ－２水平（１３９ｎｇ／Ｌ±１４ｎｇ／Ｌ，１２７μｍｏｌ／Ｌ±４０μｍｏｌ／Ｌ）明显高于ＣＨ组（８５ｎｇ／Ｌ±１５ｎｇ／Ｌ，６３μｍｏｌ／Ｌ±２５μｍｏｌ／Ｌ，Ｐ＜００１）．合并有Ⅲ，Ⅳ期肝性脑病与肝肾综合征患者外周血ＥＴ和ＮＯ－２水平（１４９ｎｇ／Ｌ±１３ｎｇ／Ｌ，１６２μｍｏｌ／Ｌ±３４μｍｏｌ／Ｌ）明显高于非肝性脑病患者（１１５ｎｇ／Ｌ±１２ｎｇ／Ｌ，８８μｍｏｌ／Ｌ±２４μｍｏｌ／Ｌ，Ｐ＜００１）和Ⅱ期肝性脑病患者（１３６ｎｇ／Ｌ±１０ｎｇ／Ｌ，１２２μｍｏｌ／Ｌ±２６μｍｏｌ／Ｌ，Ｐ＜００１）；ＬＡｒｇ静脉滴注后血浆ＥＴ水平和平均动脉压（ＭＡＰ）显著下降，而肌酐清除率（ｃＣｒ）和尿钠含量明显增加．结论ＥＴ和ＮＯ水平升高是引起ＳＨ多脏器功能障碍的重要因素．ＬＡｒｇ长期治疗可能促进ＳＨ患者脑水肿形成和肝肾综合征发生．

AIM To investigate the role of endothelin (ET) and nitric oxide (NO) in pathogenesis of severe hepatitis. METHODS The peripheral blood levels of ET and NO - 2 (metabolite of NO) were measured in 30 patients with severe hepatitis and 32 patients with chronic hepatitis. L arginine (L Arg), a substrate for NO synthase, was infused into 9 patients with severe hepatitis, and the effects were compared with those of saline infusion. RESULTS ET and NO - 2 levels were significantly higher in patients with severe hepatitis ( 139ng/L ± 14ng/L , 12 7μmol/L ± 4 0μmol/L ) than those of chronic hepatitis ( 85ng/L ± 15ng/L , 6 3μmol/L ± 2 5μmol/L , P <0 01). ET and NO - 2 levels were markedly higher in severe hepatitis with stage Ⅲ and Ⅳ of encephalopathy and hepatic renal failure ( 149ng/L ± 13ng/L , 16 2μmol/L ± 3 4μmol/L ) than in those with stage Ⅱ of encephalopathy ( 136ng/L ± 10ng/L , 12 2μmol/L ± 2 6μmol/L , P <0 01) or without encephalopathy ( 115ng/L ± 12ng/L , 8 8μmol/L ± 2 4μmol/L , P <0 01). L Arg infusion significantly decreased plasma ET levels and mean artery pressure (MAP) while markedly increased creatinine clearance (cCr) and urinary sodium excretion. CONCLUSION The increases of ET and NO levels may be important factors involved in the pathogenetic process of severe hepatitis with multiple organ dysfunction, and long term infusion of L Arg in patients with severe hepatitis may bring about hepatic renal syndrome and cerebral edema.