肝硬化中脂质过氧化增强。

Enhanced lipid peroxidation in hepatic cirrhosis.

作者信息

Pratico D, Iuliano L, Basili S, Ferro D, Camastra C, Cordova C, FitzGerald G A, Violi F

机构信息

Istituto di Clinica Medica I, University La Sapienza, Rome, Italy.

出版信息

J Investig Med. 1998 Feb;46(2):51-7.

PMID:9549227

Abstract

BACKGROUND

Lipid peroxidation is thought to play a role in the evolution of liver damage, based on evidence in experimental models. However, evidence that lipid peroxidation occurs in patients with liver disease remains to be provided. We addressed the hypothesis by measuring levels of 8-epi Prostaglandin F2 alpha a bioactive prostaglandin isomer produced by free radical catalyzed peroxidation of arachidonic acid, in patients with liver cirrhosis.

METHODS

In 42 patients with hepatic cirrhosis 8-epi Prostaglandin F2 alpha, factor VII activity, endotoxemia, carotenoids and alpha-tocopherol were measured. In 10 patients 8-epi Prostaglandin F2 alpha was also measured before and 30 days after 300 mg b.i.d. vitamin E administration.

RESULTS

Cirrhotic patients had significant higher 8-epi Prostaglandin F2 alpha, excretion than controls [median (range): 199.2 (60.0-812) vs 85.9 (55.6-160.0) pg/mg creatinine, p < 0.0001]. Patients with urinary 8-epi Prostaglandin F2 alpha above the range in controls were more likely to have moderate or severe than mild liver failure (p < 0.004). They also had lower factor VII activity (62 +/- 19 vs 74 +/- 15%, P < 0.02) than patients with normal levels of the isoprostane. Urinary excretion of 8-epi Prostaglandin F2 alpha correlated directly with endotoxemia (Rho = 0.56, p < 0.0002) and inversely with factor VII (Rho = -0.39, p < 0.02). Cirrhotic patients given vitamin E showed a significant decrease of urinary 8-epi Prostaglandin F 2 alpha [median (range): 342.5 (170 - 812) vs 292.5 (142-562) pg/mg creatinine, p < 0.04].

CONCLUSION

This study demonstrated that lipid peroxidation is increased in vivo in patients with cirrhosis and suggests that oxidant stress might contribute to the deterioration of liver disease.

摘要

背景

基于实验模型中的证据，脂质过氧化被认为在肝损伤的发展中起作用。然而，肝病患者发生脂质过氧化的证据仍有待证实。我们通过测量肝硬化患者体内8-表前列腺素F2α（一种由自由基催化花生四烯酸过氧化产生的生物活性前列腺素异构体）的水平来验证这一假设。

方法

检测42例肝硬化患者的8-表前列腺素F2α、凝血因子VII活性、内毒素血症、类胡萝卜素和α-生育酚水平。对10例患者在每日两次服用300mg维生素E之前及之后30天也进行了8-表前列腺素F2α检测。

结果

肝硬化患者的8-表前列腺素F2α排泄量显著高于对照组[中位数（范围）：199.2（60.0 - 812）对85.9（55.6 - 160.0）pg/mg肌酐，p < 0.0001]。尿8-表前列腺素F2α高于对照组范围的患者发生中度或重度肝功能衰竭的可能性大于轻度肝功能衰竭患者（p < 0.004）。他们的凝血因子VII活性也低于异前列腺素水平正常的患者（62 ± 19对74 ± 15%，P < 0.02）。尿8-表前列腺素F2α排泄量与内毒素血症直接相关（Rho = 0.56，p < 0.0002），与凝血因子VII呈负相关（Rho = - 0.39，p < 0.02）。给予维生素E的肝硬化患者尿8-表前列腺素F2α显著降低[中位数（范围）：342.5（170 - 812）对292.5（142 - 562）pg/mg肌酐，p < 0.04]。