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循环可溶性血管黏附蛋白1导致慢性肝病患者血清单胺氧化酶活性升高。

Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease.

作者信息

Kurkijärvi R, Yegutkin G G, Gunson B K, Jalkanen S, Salmi M, Adams D H

机构信息

MediCity Research Laboratories, University of Turku and National Public Health Institute Department in Turku, Turku, Finland.

出版信息

Gastroenterology. 2000 Oct;119(4):1096-103. doi: 10.1053/gast.2000.18163.

DOI:10.1053/gast.2000.18163
PMID:11040196
Abstract

BACKGROUND & AIMS: Vascular adhesion protein 1 (VAP-1) is an endothelial glycoprotein that supports adhesion of lymphocytes to hepatic endothelium and has sequence homology with semicarbazide-sensitive amine oxidases (SSAOs). We investigated whether soluble VAP-1 (sVAP-1) displays SSAO activity and thereby accounts for increased monoamine oxidase activity in the serum of patients with liver diseases.

METHODS

sVAP-1 concentration and SSAO activity were measured in peripheral, hepatic, and portal blood and in bile from patients with liver disease and in peripheral blood of control subjects, using enzyme-linked immunosorbent assay and enzymatic assays.

RESULTS

sVAP-1 concentration (mean [+/-SE], 143. 67 [34.97-92.67] ng/mL) and SSAO activity (18.8 [12.0-24.6] nmol. mL(-1). h(-1)) were significantly increased in chronic liver diseases compared with healthy controls (87.1 [53.5-127] ng/mL [P<0.001] and 10.7 [6.5-12.7] nmol. mL(-1) x h(-1) [P<0.05]) but not in massive necrosis caused by paracetamol poisoning (109 [80.3-140] ng/mL and 8.9 [5.7-12.3] nmol. mL(-1) x h(-1)). sVAP-1 correlated with serum transaminase and bilirubin but not with creatinine. In 5 paired samples, sVAP-1 concentration was higher in hepatic (median, 113 [range, 53-122]) than in portal vein (102 [42-109]; 2P<0.05), and was not detected in bile. There was a highly significant correlation between serum sVAP-1 and SSAO activity in normal subjects, patients with acute liver failure, and those with chronic liver disease (r = 0.895; P<0.001). When serum was depleted of sVAP-1 by immunoaffinity chromatography, SSAO activity was eliminated.

CONCLUSIONS

sVAP-1 levels are increased in chronic liver disease, and sVAP-1 is likely derived from the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.

摘要

背景与目的

血管黏附蛋白1(VAP-1)是一种内皮糖蛋白,可促进淋巴细胞与肝内皮的黏附,且与氨基脲敏感胺氧化酶(SSAO)具有序列同源性。我们研究了可溶性VAP-1(sVAP-1)是否具有SSAO活性,以及这是否可以解释肝病患者血清中增加的单胺氧化酶活性。

方法

采用酶联免疫吸附测定法和酶法,检测肝病患者外周血、肝血、门静脉血和胆汁以及对照受试者外周血中的sVAP-1浓度和SSAO活性。

结果

与健康对照者相比,慢性肝病患者的sVAP-1浓度(平均值[±标准误],143.67[34.97 - 92.67] ng/mL)和SSAO活性(18.8[12.0 - 24.6] nmol·mL⁻¹·h⁻¹)显著升高(分别为87.1[53.5 - 127] ng/mL[P<0.001]和10.7[6.5 - 12.7] nmol·mL⁻¹·h⁻¹[P<0.05]),但对乙酰氨基酚中毒导致的大片坏死患者则不然(109[80.3 - 140] ng/mL和8.9[5.7 - 12.3] nmol·mL⁻¹·h⁻¹)。sVAP-1与血清转氨酶和胆红素相关,但与肌酐无关。在5对配对样本中,肝内sVAP-1浓度(中位数,113[范围,53 - 122])高于门静脉(102[42 - 109];P<0.05),胆汁中未检测到。在正常受试者、急性肝衰竭患者和慢性肝病患者中,血清sVAP-1与SSAO活性之间存在高度显著的相关性(r = 0.895;P<0.001)。当通过免疫亲和层析去除血清中的sVAP-1时,SSAO活性消失。

结论

慢性肝病患者的sVAP-1水平升高,且sVAP-1可能来源于肝脏。血清sVAP-1具有SSAO活性,且是人类血清中大部分单胺氧化酶活性的来源。

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