原发性痛风性关节炎和高尿酸血症外周血脂联素及PPARγ的表达研究

Expression of adiponectin and peroxisome proliferator activated receptor γ in patients with primary gouty arthritis and asymptomatic hyperuricemia

目的:血清脂联素与代谢性疾病密切相关,同时具有调节炎性及免疫反应等功能。过氧化物酶体增殖物激活受体γ(PPARγ)是脂联素信号转导通路中的重要信号分子。本课题旨在研究脂联素及过氧化物酶体增殖物激活受体γ在原发性痛风性关节炎及高尿酸血症患者外周血的变化及临床意义。方法:采用酶联免疫吸附试验(ELISA)测定56例原发性痛风性关节炎(GA)患者、50例无症状高尿酸血症(AHU)患者及60例健康对照(CG)血清脂联素(ADP)含量,实时荧光定量聚合酶链反应(RT-q PCR)检测以上三组中各30例外周血单个核细胞(PBMNCs)中过氧化物酶体增殖物激活受体γ(PPARγ)的mRNA水平并进行比较,分析ADP、PPARγ与GA、AHU临床及实验室指标的相关性。组间比较采用方差分析,相关分析采用Pearson法进行统计学分析。结果:1三组的血尿酸、空腹血糖、甘油三酯、收缩压、舒张压、体质量指数(BMI),差异均有统计学意义(P均<0.05);2三组ADP水平差异有统计学意义(P<0.01),进一步两两分析GA组血清脂联素水平(5.31±2.63)μg/m L显著低于CG组(8.63±6.07)μg/m L(P<0.05),AHU组血清脂联素水平(5.67±3.67)μg/m L也显著低于CG组(P<0.05),但GA组和AHU组的血清ADP之间并无显著性差异;3GA组PBMNCs中PPARr mRNA表达量(0.80±0.46)高于CG组(0.37±0.07)(P<0.05),GA组与AHU组PBMNCs中PPARr mRNA相比较(0.80±0.46 vs 0.39±0.37)差异有统计学意义(P<0.05),但AHU组与GC组PBMNCs中PPARr mRNA差异无统计学意义;4相关性分析发现GA组ADP与血尿酸水平、空腹血糖及甘油三酯之间均呈负相关(P<0.05),AHU组ADP与血尿酸、BMI之间呈负相关(P<0.05);5GA组PBMNCs PPARr mRNA与CRP、ESR之间呈正相关(P<0.05),AHU组PBMNCs PPARr mRNA与甘油三酯之间呈负相关(P<0.05)。结论:脂联素及PPARr表达异常可能参与了原发性痛风性关节炎和高尿酸血症的发生发展,可能与痛风的炎症及代谢过程密切相关。

Objective：To investigate the role of adiponectin（ADP）and peroxisome proliferator- activated receptor γ （PPARγ） in patients with primly gouty arthritis （GA） and asymptomatic hyperuricemia （AHU）. Methods： Enzyme - linked immunosorbent assay （ELISA）was used to determine the levels of serum ADP in GA （ n = 56）, AHU （ n = 50）, healthy controls group（CG） （n = 60）. Real time quantitative polymerase chain reaction （RT- qPCR）was employed to study the expression of PPAR3, rnR_NA in peripheral blood mononuclear cells（PBMCs）. All subjects completed physical examination, biochemical measurements at the same time. Analysis of variance and Pearson＇s correlation analysis were used for statistical analysis. Results：①The concentrations of serum ADP were significandy different in the three groups （ P 〈0.01 ） . The expression levels of serum ADP were lower in GA compared with CG, （5.31 ±2.63） μg/mL vs （8.63 ±6.07）μg/mL （P 〈0.05）. There were no significant difference between the level of ADP in GA and AHU;②he ex- pressions of PPARγ mRNA were significantly different in the three groups （ F = 7.081, P 〈 0. 01 ）. The expressions of PPARγmRNA were significantly higher in GA than AHU （0.80 ±0.46 vs 0.39 ±0.37,P 〈0.05） and CG（0. 80 ±0.46 vs 0.37 ±0.07,P 〈0.05）. There were no significant difference between the expressions of PPARγ/mRNA in AHU and CG;③In the GA patients, the level of ADP was negatively correlated with the blood uric acid（UA）, fasting blood glu- cose（FBG） and triglyceride（TG）（P 〈0.05）;The expression of PPARγ/mRNA was positively correlated with CRP and ESR level（P 〈0.05） ;④In the AHU patients, the level of ADP was negatively correlated with the UA and body mass in- dex（BMI） （P 〈0.05）;⑤The expression of PPAR＇,/mRNA was negatively correlated with TG （P 〈0.05）. Conclusion： Altered expression of ADP may be involved in the pathogenesis of metabolic disorder in GA and AHU. The PPAR~/may be a key role in the pathogenesis of of gouty inflammation.