Tabernero Antonia, Schneider Francis, Potenza Maria Assunta, Randriamboavonjy Voahanginirina, Chasserot Sylvette, Wolf Philippe, Mitolo-Chieppa Delia, Stoclet Jean-Claude, Andriantsitohaina Ramaroson
Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS (UMR 7034), Illkirch, France.
Intensive Care Med. 2003 Feb;29(2):262-70. doi: 10.1007/s00134-002-1617-7. Epub 2003 Jan 15.
To investigate the expression of inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) and the role of vasodilatory prostanoids and endogenous nitric oxide (NO) in small omental arteries harvested from patients with severe liver diseases.
Ex vivo study of resistance arteries. SETTING. Intensive care unit.
Twenty patients undergoing liver transplantation for fulminant hepatic failure (FHF, n=6), cirrhogenous viral hepatitis (CH, n=6) and limited hepatocarcinoma (controls, n=8).
Western blot and immunohistochemical labeling for assessment of COX-2 and iNOS expression and localization and ex vivo vascular reactivity studies.
Significant upregulation of COX-2 and iNOS expressions were detected in arteries from FHF and CH patients with a greater increase in the former than in the latter. Ex vivo contractile responses to norepinephrine and the thromboxane A(2) analog, U46619, were not significantly different between patients with severe liver dysfunction and controls. Exposure to either the NO-synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), the cyclooxygenase inhibitor, indomethacin, or their combination did not significantly modify contractions of agonists in controls and CH patients. In FHF, the specific COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (1 micro m/l), but not L-NAME, significantly enhanced the maximal effect ( p<0.01) and the sensitivity ( p<0.01) to norepinephrine.
COX-2 and iNOS are upregulated in omental arteries from patients with cirrhogenous hepatitis and fulminant hepatic failure. Whereas neither NO nor vasodilatory prostaglandins seem to play a major role in counteracting arterial contractility of arteries from control patients, COX-2 derivatives are involved in lowering the arterial contractility of vessels harvested from FHF patients.
研究诱导型环氧化酶（COX-2）和诱导型一氧化氮合酶（iNOS）的表达，以及血管舒张性前列腺素和内源性一氧化氮（NO）在重症肝病患者小网膜动脉中的作用。
对阻力动脉进行离体研究。地点：重症监护病房。
20例接受肝移植的患者，其中暴发性肝衰竭（FHF，n = 6）、肝硬化病毒性肝炎（CH，n = 6）和局限性肝癌（对照组，n = 8）。
采用蛋白质印迹法和免疫组织化学标记法评估COX-2和iNOS的表达及定位，并进行离体血管反应性研究。
在FHF和CH患者的动脉中检测到COX-2和iNOS表达显著上调，前者的上调幅度大于后者。重症肝功能不全患者与对照组对去甲肾上腺素和血栓素A2类似物U46619的离体收缩反应无显著差异。给予一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯（L-NAME）、环氧化酶抑制剂吲哚美辛或二者联合应用，对对照组和CH患者激动剂引起的收缩无显著影响。在FHF患者中，特异性COX-2抑制剂N-(2-环己氧基-4-硝基苯基)甲磺酰胺（1 μmol/l）而非L-NAME，可显著增强对去甲肾上腺素的最大效应（p<0.01）和敏感性（p<0.01）。
在肝硬化性肝炎和暴发性肝衰竭患者的网膜动脉中，COX-2和iNOS上调。虽然NO和血管舒张性前列腺素在抵消对照组患者动脉收缩性方面似乎均不起主要作用，但COX-2衍生物参与降低FHF患者血管的动脉收缩性。
