Ivanišević Jasmina, Kotur-Stevuljević Jelena, Stefanović Aleksandra, Spasić Slavica, Vučinić Mihailović Violeta, Videnović Ivanov Jelica, Jelić-Ivanović Zorana
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Clinic for Pulmonary Diseases and Tuberculosis, Clinical Centre of Serbia, Belgrade, Serbia.
Eur J Clin Invest. 2016 May;46(5):418-24. doi: 10.1111/eci.12610. Epub 2016 Mar 17.
It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis.
Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects.
HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration.
We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.
据报道，高密度脂蛋白（HDL）颗粒由于对氧磷酶1（PON1）等不同酶的作用而具有抗炎和抗氧化作用。在炎症和氧化应激条件下，HDL颗粒可能会失去其保护特性。结节病是一种以过度氧化应激为特征的炎症性疾病。血清淀粉样蛋白A（SAA）在肝脏和肉芽肿中产生，其浓度在炎症状态下升高，导致HDL颗粒分解代谢增加。我们研究的目的是确定结节病患者的PON1活性、SAA浓度及其相关性。
测定72例结节病患者和62例健康受试者血清中的炎症指标[高敏C反应蛋白（hsCRP）、血管紧张素转换酶（ACE）、SAA]、脂质指标[总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-c）、低密度脂蛋白胆固醇（LDL-c）、甘油三酯（TG）]、氧化应激状态参数[总氧化剂状态（TOS）、丙二醛（MDA）、促氧化剂-抗氧化剂平衡（PAB）、巯基（SH）基团]和PON1活性。
与对照组相比，结节病患者的hsCRP（P<0.05）、TC、LDL-c、TG、SAA、TOS、MDA和PAB（P<0.001）显著升高，而HDL-c、SH基团和PON1活性（P<0.001）显著降低。PON1与SAA、MDA和PAB显著相关。结果表明，PON1活性降低71%可能是由于TOS、PAB和SAA浓度升高所致。
我们发现结节病患者PON1活性降低，SAA浓度升高。高SAA所呈现的炎症状态与HDL功能受损有关，这通过PON1活性失调得以体现。过度氧化应激也参与了PON1活性的失调。
