Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
Cytokine. 2012 Aug;59(2):442-9. doi: 10.1016/j.cyto.2012.05.001. Epub 2012 May 31.
The liver is a major target of injury in obese patients. Non-alcoholic fatty liver disease (NAFLD) is present in 60-90% of obese Americans and can range from simple steatosis to the more severe non-alcoholic steatohepatitis (NASH). The onset of a chronic inflammatory reaction marks the progression from simple steatosis to NASH and the expansion of adipose tissue is strongly associated with angiogenesis. Therefore, we determined the serum concentration of inflammatory [tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6)] and angiogenic [vascular endothelial growth factor A (VEGF)] cytokines and soluble VEGF receptors 1 and 2 (sVEGFR1, sVEGFR2) in the serum of an obese population with simple steatosis and NASH compared to healthy controls. Moreover, we determined the TNFα, IL6, VEGF, VEGFR1 and VEGFR2 gene expression in the liver of these simple steatosis and NASH patients. The population consisted of 30 obese patients, which were diagnosed with simple steatosis and 32 patients with NASH and compared to 30 age-and-sex matched healthy controls. Mean serum TNFα levels were elevated in the serum of simple steatosis and NASH patients compared to healthy controls, reaching significance in NASH patients. IL6 was significantly increased in simple steatosis and NASH patients compared to the healthy controls. VEGF levels were significantly elevated in patients with simple steatosis and borderline significantly elevated in NASH patients compared to the serum levels of healthy control subjects. The concentration of sVEGFR1 was significantly increased in serum of simple steatosis and NASH patients compared to controls. sVEGFR2 concentration was not significantly different in the three groups. TNFα mRNA expression was higher in NASH patients compared to simple steatosis patients. Hepatic gene expression of VEGF, VEGFR1 and VEGFR2 were slightly decreased in NASH patients compared to simple steatosis patients. These data indicate the involvement of inflammatory (TNFα and IL6), angiogenic (VEGF) cytokines and sVEGFR1 in the pathophysiology of NAFLD.
肝脏是肥胖患者损伤的主要靶器官。非酒精性脂肪性肝病（NAFLD）在美国肥胖人群中的发生率为 60-90%，可从单纯性脂肪变性发展为更严重的非酒精性脂肪性肝炎（NASH）。慢性炎症反应的发生标志着单纯性脂肪变性向 NASH 的进展，脂肪组织的扩张与血管生成强烈相关。因此，我们测定了单纯性脂肪变性和 NASH 肥胖患者与健康对照组相比血清中炎症（肿瘤坏死因子α（TNFα）和白细胞介素 6（IL6））和血管生成（血管内皮生长因子 A（VEGF））细胞因子以及可溶性血管内皮生长因子受体 1 和 2（sVEGFR1、sVEGFR2）的浓度。此外，我们还测定了这些单纯性脂肪变性和 NASH 患者肝脏中 TNFα、IL6、VEGF、VEGFR1 和 VEGFR2 的基因表达。该人群由 30 名被诊断为单纯性脂肪变性的肥胖患者和 32 名 NASH 患者组成，并与 30 名年龄和性别匹配的健康对照者进行比较。与健康对照组相比，单纯性脂肪变性和 NASH 患者血清中 TNFα 水平升高，NASH 患者 TNFα 水平升高具有统计学意义。与健康对照组相比，单纯性脂肪变性和 NASH 患者的 IL6 水平明显升高。与健康对照组相比，单纯性脂肪变性患者和 NASH 患者的 VEGF 水平明显升高，而 NASH 患者的 VEGF 水平略有升高。与对照组相比，单纯性脂肪变性和 NASH 患者血清中 sVEGFR1 的浓度明显升高。三组间 sVEGFR2 浓度无显著差异。与单纯性脂肪变性患者相比，NASH 患者的 TNFαmRNA 表达更高。与单纯性脂肪变性患者相比，NASH 患者肝组织中 VEGF、VEGFR1 和 VEGFR2 的基因表达略有下降。这些数据表明炎症（TNFα和 IL6）、血管生成（VEGF）细胞因子和 sVEGFR1 参与了 NAFLD 的病理生理学过程。
