痛风患者外周血NALP3炎性体与炎性因子、糖脂代谢的相关性

Correlation between NALP3 Inflammasome and Inflammatory Cytokines or Glycolipid Metabolism in Patients with Gout

目的探讨痛风患者外周血NALP3炎性体与炎性因子、糖脂代谢的相关性。方法分别选择102例痛风患者(痛风组)、154例高尿酸血症患者(高尿酸血症组)和107例健康体检人群(对照组)作为研究对象,收集3组受试对象年龄、体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、尿酸(UA)、空腹血糖(FPG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、总胆固醇(TC)等临床资料,采用RT-PCR和Western blot检测各组患者外周血NALP3mRNA和蛋白表达。另利用100μg/mL尿酸盐刺激对照组全血6h,再次检测刺激组与未刺激组外周血单个核细胞(PBMCs)NALP3mRNA和蛋白表达。结果痛风组和高尿酸血症组BMI、FPG、LDL-C、TG、TC、UA、TNF-α、IL-1β、C反应蛋白(CRP)明显高于对照组,脂联素(APN)明显低于对照组,差异具有统计学意义(均P<0.05);痛风组FPG、LDL-C、TG、TC、UA、IL-1β、CRP明显高于高尿酸血症组,APN明显低于高尿酸血症组,差异具有统计学意义(均P<0.05)。NALP3mRNA在痛风组(0.846±0.130)、高尿酸血症组(0.700±0.126)的表达明显高于对照组(0.231±0.049),痛风组NALP3mRNA表达量明显高于高尿酸血症组,差异均有统计学意义(均P<0.05)。对照组外周血经尿酸盐刺激后,刺激组NALP3mRNA和蛋白表达较相应空白组显著升高(均P<0.05)。痛风组和高尿酸血症组NALP3mRNA表达与FPG、UA、TNF-α、IL-1β、CRP呈正相关,与APN呈负相关(均P<0.05)。校正BMI、FPG、TG、TC等混杂因素后,结果显示NALP3mRNA不是高尿酸血症发生的危险因素,而NALP3mRNA表达≥0.808是痛风发生的危险因素(P<0.05)。结论痛风患者NALP3表达明显升高,NALP3可能参与痛风的发病和进展。

Objective To investigate the correlation between NALP3 inflammasome and inflammatory cytokines,or glycolipid metabolism in patients with gout.Methods A total of 102 gout patients(gout group),154 hyperuricemia patients(hyperuricemia group)and 107 health check-up individuals(control group)were enrolled in this study.The clinical data such as age,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),uric acid(UA),fast blood glucose(FPG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglyceride(TG),total cholesterol(TC)were collected.The levels of NALP3 mRNA and protein in the peripheral blood were measured by RT-PCR and Western blotting,respectively.Urate(100μg/mL)was used to stimulate the peripheral blood for 6 h,and the expression of NALP3 mRNA and protein was detected in peripheral blood mononuclear cells(PBMCs).Results The levels of BMI,FPG,LDL-C,TG,TC,UA,TNF-α,IL-1β,and CRP were much higher and the levels of APN were significantly lower in the gout group and the hyperuricemia group than those in the control group(P<0.05).The levels of FPG,LDL-C,TG,TC,UA,TNF-α,IL-1β,and CRP were significantly higher and the levels of APN obviously lower in the gout group than those in the hyperuricemia group(P<0.05).The expression of NALP3 mRNA was significantly increased in the gout group and the hyperuricemia group as compared with that in the control group[(0.846±0.130),(0.700±0.126)vs.(0.231±0.049)],with NALP3 mRNA expression higher in the gout group than in the hyperuricemia group(P<0.05).Compared with that in the blank control group,the expression of NALP3 mRNA and protein was significantly enhanced after stimulation with 100μg/mL of urate(P<0.05).There was a positive correlation between NALP3 mRNA and FPG,UA,TNF-α,IL-1β,or CPR,and a negative correlation between NALP3 mR-NA and APN in the gout group and hyperuricemia group(all P<0.05).After adjusting for confounding factors BMI,FPG,TG and TC,the high level of NALP3 mRNA(≥0.808)was found to be a risk factor for gout(P<0.05).Conclusion NALP3 is significantly elevated in patients with gout,suggesting that NALP3 may be involved in the pathogenesis of gout.