暴发性肝衰竭患者血浆中转化生长因子-β1水平及肝脏mRNA表达情况

Plasma levels and hepatic mRNA expression of transforming growth factor-beta1 in patients with fulminant hepatic failure.

作者信息

Miwa Y, Harrison P M, Farzaneh F, Langley P G, Williams R, Hughes R D

机构信息

Institute of Liver Studies, King's College School of Medicine and Dentistry, London, UK.

出版信息

J Hepatol. 1997 Nov;27(5):780-8. doi: 10.1016/s0168-8278(97)80313-3.

DOI:10.1016/s0168-8278(97)80313-3

PMID:9382963

Abstract

BACKGROUND/AIMS: Transforming growth factor-beta1 is an important cytokine involved in cell growth and inflammation which has been shown to be inhibitory to hepatic DNA synthesis. The aim of this study was to investigate the plasma levels and hepatic mRNA expression of transforming growth factor-beta1 in patients with fulminant hepatic failure in whom liver regeneration may be impaired.

METHODS

Plasma levels of transforming growth factor-beta1 and human hepatocyte growth factor were measured in 57 fulminant hepatic failure patients and 20 healthy volunteers by ELISA. Northern blot analysis of transforming growth factor-beta1 and H3 histone, a marker for liver proliferation, was performed in liver tissue of 14 fulminant hepatic failure patients.

RESULTS

The plasma levels of total transforming growth factor-beta1 in fulminant hepatic failure patients on admission (median 38.8 ng/ml, range 8.4-108 ng/ml) were significantly higher than those in control subjects (23.0 ng/ml, 8.5-34.9 ng/ml, p<0.001). Significantly higher levels were observed in non-A, non-B hepatitis patients (57.9 ng/ml, 38.8-108 ng/ml, n=10, p<0.001) compared to patients with paracetamol overdose (37.1 ng/ml, 8.4-72.5 ng/ml, n=47). In contrast, the plasma levels of free transforming growth factor beta1 were greater in paracetamol overdose (623 pg/ml, 46.7-1241 pg/ml, n=21) than in non-A, non-B hepatitis (131 pg/ml, 77.2-254 pg/ml, n=9), with both being higher than control (72.3 pg/ml, 28.7-108, n=7, p<0.001). The plasma levels of human hepatocyte growth factor in patients with paracetamol overdose (7.04 ng/ml, 1.00-62.4 ng/ml) were significantly higher than those in patients with non-A, non-B hepatitis (4.48 ng/ml, 0.74-9.10 ng/ml, p<0.05). Northern blots showed increased mRNA expression of transforming growth factor-beta1 in paracetamol-overdose patients (n=8, p<0.05), but not in patients with non-A non-B hepatitis (n=6), compared to controls (n=4).

CONCLUSIONS

The increased circulating plasma TGF-beta1 in FHF may be part of the tissue repair process in fulminant hepatic failure. In patients with non-A, non-B hepatitis, the increased total transforming growth factor-beta1 together with a less elevated hepatocyte growth factor could be related to impaired liver regeneration in this group.

摘要

背景/目的：转化生长因子β1是一种参与细胞生长和炎症反应的重要细胞因子，已被证明对肝脏DNA合成具有抑制作用。本研究旨在调查暴发性肝衰竭患者中转化生长因子β1的血浆水平及肝脏mRNA表达情况，这类患者的肝脏再生可能受损。

方法

采用酶联免疫吸附测定法（ELISA）检测了57例暴发性肝衰竭患者和20名健康志愿者血浆中转化生长因子β1和人肝细胞生长因子的水平。对14例暴发性肝衰竭患者的肝组织进行了转化生长因子β1和H3组蛋白（肝脏增殖标志物）的Northern印迹分析。

结果

暴发性肝衰竭患者入院时血浆中总转化生长因子β1水平（中位数38.8 ng/ml，范围8.4 - 108 ng/ml）显著高于对照组（23.0 ng/ml，8.5 - 34.9 ng/ml，p<0.001）。与对乙酰氨基酚过量患者（37.1 ng/ml，8.4 - 72.5 ng/ml，n = 47）相比，非甲非乙型肝炎患者（57.9 ng/ml，38.8 - 108 ng/ml，n = 10，p<0.001）的该水平显著更高。相反，对乙酰氨基酚过量患者（623 pg/ml，46.7 - 1241 pg/ml，n = 21）血浆中游离转化生长因子β1水平高于非甲非乙型肝炎患者（131 pg/ml，77.2 - 254 pg/ml，n = 9），两者均高于对照组（72.3 pg/ml，28.7 - 108，n = 7，p<0.001）。对乙酰氨基酚过量患者血浆中人肝细胞生长因子水平（7.04 ng/ml，1.00 - 62.4 ng/ml）显著高于非甲非乙型肝炎患者（4.48 ng/ml，0.74 - 9.10 ng/ml，p<0.05）。Northern印迹显示，与对照组（n = 4）相比，对乙酰氨基酚过量患者（n = 8，p<0.05）肝脏中转化生长因子β1的mRNA表达增加，而非甲非乙型肝炎患者（n = 6）未增加。