非酒精性脂肪性肝炎患者的血清泛素水平

Savas M Cemil, Koruk Mehmet, Pirim Ibrahim, Yilmaz Omer, Karakok Metin, Taysi Seyithan, Yilmaz Arif

Department of Internal Medicine, Division of Gastroenterology, University of Gaziantep, Gaziantep, Turkey.

Hepatogastroenterology. 2003 May-Jun;50(51):738-41.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis is increasingly recognized as the most common liver disease in patients with elevated liver enzymes. In the pathophysiology of nonalcoholic steatohepatitis, the first step is the lipid accumulation in the liver causing steatosis, the second step involves the endotoxins, cytokines and environmental toxins causing oxidative stress and lipid peroxidation, in time leading to steatohepatitis. Ubiquitin is a molecular chaperone that plays a major role in the degradation of intracellular proteins. Ubiquitin proteasome system is also considered as a cellular defense mechanism that removes damaged proteins generated by oxidative stress. In order to search for the role of ubiquitin in the pathogenesis of nonalcoholic steatohepatitis, serum levels of ubiquitin were studied in patients with nonalcoholic steatohepatitis for the first time in the literature, to our knowledge.

METHODOLOGY

Eighteen patients with biopsy proven nonalcoholic steatohepatitis diagnosis (13 males and 5 females with a mean age of 41) and 16 healthy volunteers as a control group (11 males and 5 females, with a mean age of 38) were included in the study. Serum ubiquitin levels were studied by ELISA method.

RESULTS

The mean serum ubiquitin level (14.13 +/- 1.46 micrograms/mL) in patients with nonalcoholic steatohepatitis was significantly elevated compared to that of the control group (7.66 +/- 0.40 micrograms/mL) (p < 0.001). No correlation was found among serum ubiquitin levels and hepatic steatosis, inflammation and fibrosis.

CONCLUSIONS

Increased serum ubiquitin levels may show that the ubiquitin proteasome pathway actively participates in defending against oxidative stress in nonalcoholic steatohepatitis. Serum ubiquitin concentration may be a marker predicting the intracellular cytoprotective response against oxidative stress rather than the degree of liver damage in pathogenesis of nonalcoholic steatohepatitis. Ubiquitin proteasome system based therapies may have a place in the treatment of patients with nonalcoholic steatohepatitis in the future.

背景/目的：非酒精性脂肪性肝炎日益被认为是肝酶升高患者中最常见的肝脏疾病。在非酒精性脂肪性肝炎的病理生理学中，第一步是肝脏中的脂质蓄积导致脂肪变性，第二步涉及内毒素、细胞因子和环境毒素引起氧化应激和脂质过氧化，最终导致脂肪性肝炎。泛素是一种分子伴侣，在细胞内蛋白质降解中起主要作用。泛素蛋白酶体系统也被视为一种细胞防御机制，可清除由氧化应激产生的受损蛋白质。据我们所知，为了探寻泛素在非酒精性脂肪性肝炎发病机制中的作用，本研究首次在文献中对非酒精性脂肪性肝炎患者的血清泛素水平进行了研究。