Crespo J, Cayón A, Fernández-Gil P, Hernández-Guerra M, Mayorga M, Domínguez-Díez A, Fernández-Escalante J C, Pons-Romero F
Institute of Digestive Diseases, University Hospital Marqués de Valdecilla, School of Medicine, Santander, Spain.
Hepatology. 2001 Dec;34(6):1158-63. doi: 10.1053/jhep.2001.29628.
The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-alpha and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-alpha, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-alpha was found in patients with NASH in hepatic tissue (0.65 +/- 0.54) and in peripheral fat (0.43 +/- 0.45); in the control samples, the mRNA expression was 0.28 +/- 0.32, P <.007, and 0.26 +/- 0.22, P <.018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 +/- 1.81 vs. 1.56 +/- 1.17; P <.05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-alpha in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-alpha mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-alpha system may be involved in the pathogenesis of NASH.
本研究的主要目的是分析肿瘤坏死因子α（TNF-α）系统在非酒精性脂肪性肝炎（NASH）发病过程中的致病作用。对52例肥胖患者进行了研究。我们调查了：（1）通过定量逆转录聚合酶链反应（RT-PCR）检测肝组织和脂肪组织中TNF-α及其p55和p75受体的mRNA表达；（2）TNF-α、p55和p75与NASH严重程度之间的关系。无NASH的肥胖患者作为对照组。在NASH患者的肝组织（0.65±0.54）和外周脂肪（0.43±0.45）中发现TNF-α的mRNA表达显著增加；在对照样本中，mRNA表达分别为0.28±0.32，P<0.007和0.26±0.22，P<0.018。此外，我们发现p55受体的mRNA水平显著增加（2.42±1.81对1.56±1.17；P<0.05）；然而，p75受体的mRNA表达在两组患者中相似。与轻度或无纤维化的患者相比，有明显纤维化的NASH患者TNF-α的mRNA表达增加。在NASH患者的肝脏和脂肪组织中发现TNF-αmRNA的过表达。NASH患者肝组织中mRNA-p55水平升高。在NASH更严重的患者中，这种过表达更高。这些发现表明TNF-α系统可能参与了NASH的发病机制。
