痛风患者外周血NALP3炎性体与炎性因子、糖脂代谢的相关性
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摘要
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.
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.
引文
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[3]于飞,叶丛,凃巍,等.影响痛风患者降尿酸治疗疗效的因素分析[J].中华风湿病学杂志,2017,21(2):110-113.
[4]Zhang Q B,Qing Y F,Yin C C,et al.Mice with miR-146adeficiency develop severe gouty arthritis via dysregulation of TRAF 6,IRAK 1and NALP3inflammasome[J].Arthritis Res Ther,2018,20(1):45.
[5]Anders H J,Suarez-Alvarez B,Grigorescu M,et al.The macrophage phenotype and inflammasome component NLRP3contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1-mediated tissue injury[J].Kidney Int,2018,93(3):656-669.
[6]蔡晓燕,董光富.非布司他对慢性痛风性关节炎中NALP3炎性体的作用及意义[J].实用医学杂志,2017,33(21):3602-3605.
[7]段宇,刘超.《高尿酸血症和痛风治疗中国专家共识》解读[J].国际内分泌代谢杂志,2013,33(6):376-378.
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[9]Ruiz-Miyazawa K W,Pinho-Ribeiro F A,Borghi S M,et al.Hesperidin methylchalcone suppresses experimental gout arthritis in mice by inhibiting NF-κB activation[J].J Agric Food Chem,2018,66(25):6269-6280.
[10]Huang J,Zhou Z,Zhou M,et al.Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives targeting innate immune sensors and xanthine oxidase for treatment of gout[J].Bioorg Med Chem,2018,26(8):1653-1664.
[11]Soundara Rajan T,Giacoppo S,Diomede F,et al.Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3inflammasome activation in experimental autoimmune encephalomyelitis[J].Int J Immunopathol Pharmacol,2017,30(3):238-252.
[12]Ge H,Tang H,Liang Y,et al.Rhein attenuates inflammation through inhibition of NF-κB and NALP3inflammasome in vivo and in vitro[J].Drug Des Devel Ther,2017,11:1663-1671.
[13]Xiao J,Zhang X L,Fu C,et al.Soluble uric acid increases NALP3inflammasome and interleukin-1βexpression in human primary renal proximal tubule epithelial cells through the Toll-like receptor 4-mediated pathway[J].Int J Mol Med,2015,35(5):1347-1354.
[14]Xiao J,Fu C,Zhang X,et al.Soluble monosodium urate,but not its crystal,induces toll like receptor 4-dependent immune activation in renal mesangial cells[J].Mol Immunol,2015,66(2):310-318.
[15]Kawada T.Serum uric acid and metabolic components with special reference to diabetes mellitus[J].Clin Chim Acta,2018,484:304.
[16]Han T,Meng X,Shan R,et al.Temporal relationship between hyperuricemia and obesity,and its association with future risk of type 2diabetes[J].Int J Obes(Lond),2018,42(7):1336-1344.
[17]Ohno S,Kohjitani A,Miyata M,et al.Recovery of endothelial function after minor-to-moderate surgery is impaired by diabetes mellitus,obesity,hyperuricemia and sevoflurane-based anesthesia[J].Int Heart J,2018,59(3):559-565.
[18]Mahbub M H,Yamaguchi N,Takahashi H,et al.Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus,dyslipidemia,hypertension and metabolic syndrome[J].Sci Rep,2017,7(1):17616.
[2]Zleik N,Elfishawi M M,Kvrgic Z,et al.Hospitalization increases the risk of acute arthritic flares in gout:A populationbased study over 2decades[J].J Rheumatol,2018,45(8):1188-1191.
[3]于飞,叶丛,凃巍,等.影响痛风患者降尿酸治疗疗效的因素分析[J].中华风湿病学杂志,2017,21(2):110-113.
[4]Zhang Q B,Qing Y F,Yin C C,et al.Mice with miR-146adeficiency develop severe gouty arthritis via dysregulation of TRAF 6,IRAK 1and NALP3inflammasome[J].Arthritis Res Ther,2018,20(1):45.
[5]Anders H J,Suarez-Alvarez B,Grigorescu M,et al.The macrophage phenotype and inflammasome component NLRP3contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1-mediated tissue injury[J].Kidney Int,2018,93(3):656-669.
[6]蔡晓燕,董光富.非布司他对慢性痛风性关节炎中NALP3炎性体的作用及意义[J].实用医学杂志,2017,33(21):3602-3605.
[7]段宇,刘超.《高尿酸血症和痛风治疗中国专家共识》解读[J].国际内分泌代谢杂志,2013,33(6):376-378.
[8]Nuki G.An appraisal of the 2012American College of Rheumatology Guidelines for the Management of Gout[J].Curr Opin Rheumatol,2014,26(2):152-161.
[9]Ruiz-Miyazawa K W,Pinho-Ribeiro F A,Borghi S M,et al.Hesperidin methylchalcone suppresses experimental gout arthritis in mice by inhibiting NF-κB activation[J].J Agric Food Chem,2018,66(25):6269-6280.
[10]Huang J,Zhou Z,Zhou M,et al.Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives targeting innate immune sensors and xanthine oxidase for treatment of gout[J].Bioorg Med Chem,2018,26(8):1653-1664.
[11]Soundara Rajan T,Giacoppo S,Diomede F,et al.Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3inflammasome activation in experimental autoimmune encephalomyelitis[J].Int J Immunopathol Pharmacol,2017,30(3):238-252.
[12]Ge H,Tang H,Liang Y,et al.Rhein attenuates inflammation through inhibition of NF-κB and NALP3inflammasome in vivo and in vitro[J].Drug Des Devel Ther,2017,11:1663-1671.
[13]Xiao J,Zhang X L,Fu C,et al.Soluble uric acid increases NALP3inflammasome and interleukin-1βexpression in human primary renal proximal tubule epithelial cells through the Toll-like receptor 4-mediated pathway[J].Int J Mol Med,2015,35(5):1347-1354.
[14]Xiao J,Fu C,Zhang X,et al.Soluble monosodium urate,but not its crystal,induces toll like receptor 4-dependent immune activation in renal mesangial cells[J].Mol Immunol,2015,66(2):310-318.
[15]Kawada T.Serum uric acid and metabolic components with special reference to diabetes mellitus[J].Clin Chim Acta,2018,484:304.
[16]Han T,Meng X,Shan R,et al.Temporal relationship between hyperuricemia and obesity,and its association with future risk of type 2diabetes[J].Int J Obes(Lond),2018,42(7):1336-1344.
[17]Ohno S,Kohjitani A,Miyata M,et al.Recovery of endothelial function after minor-to-moderate surgery is impaired by diabetes mellitus,obesity,hyperuricemia and sevoflurane-based anesthesia[J].Int Heart J,2018,59(3):559-565.
[18]Mahbub M H,Yamaguchi N,Takahashi H,et al.Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus,dyslipidemia,hypertension and metabolic syndrome[J].Sci Rep,2017,7(1):17616.