Zuwała-Jagiełło Jolanta, Pazgan-Simon Monika, Simon Krzysztof, Warwas Maria
Department of Pharmaceutical Biochemistry, Liver Diseases and Acquired Immune Deficiency, Wrocław Medical University, Wrocław, Poland.
Acta Biochim Pol. 2011;58(1):59-65. Epub 2011 Mar 14.
Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.
晚期氧化蛋白产物(AOPPs)是具有促炎特性的氧化应激蛋白标志物,在肝硬化中会蓄积。在本研究中,我们调查了由AOPPs引发的慢性炎症反应与通过Child-Pugh评分评估的肝脏疾病严重程度之间的关联。对41例丙型肝炎病毒(HCV)相关肝硬化患者、43例酒精性肝硬化(ALC)患者以及30例年龄和性别匹配的对照者,测量了血浆中AOPPs以及炎症标志物如C反应蛋白、肿瘤坏死因子-α和白细胞介素-6的浓度。与对照者相比,AOPPs在HCV相关的代偿期(Child-Pugh A级)和失代偿期(Child-Pugh B - C级)肝硬化以及酒精性代偿期肝硬化中均升高。在酒精性肝硬化中,AOPPs水平与Child-Pugh评分呈正相关,而在HCV相关肝硬化中则无此相关性,且在ALC中与慢性炎症指标的相关性更强。反过来,HCV相关肝硬化中的AOPPs与炎症的关系较小,但与抗氧化防御存在显著相关性。总之,肝硬化与AOPPs生成增加有关,在酒精性肝硬化和HCV相关肝硬化之间,AOPPs与抗氧化防御、肝硬化阶段及炎症反应的关系存在差异。AOPPs蓄积与慢性炎症指标(尤其是肿瘤坏死因子-α)之间的显著相关性表明,氧化应激可能是酒精性肝硬化早期慢性炎症状态的介导因素。