Expression And Significance Of High Mobility Group Box1Protein And Its Receptor For Advanced Glycation End Products In Patients With Primary Gouty Arthritis

Objective: To investigate the role of high mobility group box1protein(HMGB1) and the receptor for advanced glycation end products(RAGE) inthe pathogenesis of primary gouty arthritis (GA).Methods:(1)Enzyme-linked immunosorbent assay（ELISA) was used todetermine the level of plasma HMGB1in68acute gout(AG),48intercriticalgout(IG) and45heathy control(HC).(2)Real-time quantitative polymerasechain reaction(RT-qPCR) was employed to study the expression of HMGB1and RAGE mRNA in peripheral blood mononuclear cells (PBMCs) in68AG,48IG and94HC,and the differences of gene expression in two groupswere compared.(3)Western blot（WB）was used to measure HMGB1inPBMCs from18AG,13IG and21HC,REGE in PBMCs from12GA and8HC,and the otherness of protein expression in two groups werecompared.(4)Analysis of T test and covariance or Wilcoxon test andSpearman’s correlations were used for statistical analysis.Results: The level of plasma HMGB1,PBMCs HMGB1, RAGE mRNAand protein were significantly higher in GA than that in HC (plasma HMGB1(ng/mL):222.00±178.32vs106.99±175.79vs23.88±34.05;PBMCs HMGB1mRNA:0.235±0.954vs0.044±0.117vs0.019±0.029;PBMCs RAGE mRAN：0.0015±0.0035vs0.0013±0.0009vs0.0005±0.0003;HMGB1protein:3.59±2.49vs1.89±2.00vs0.74±0.78；P<0.05）),while the level of plasma HMGB1andPBMCs HMGB1mRNA were significantly higher in AG than that in IG (P<0.05),the level of PBMCs RAGE protein was higher in GA than that inHC(2.94±0.67vs1.61±0.51;P<0.05),and the level of PBMCs RAGE mRNAwas higher in AG than that in IG (P>0.05). In the GA patients, the level ofplasma HMGB1was positively correlated with white blood cell,neutrophilegranulocyte, mononuclear cell and erythrocyte sedimentation rate(r=0.34,0.44,0.39,0.33;P<0.05),while negatively correlated withapolipoprotein A1(r=-0.28;P<0.05); the level of PBMCs HMGB1mRNA waspositively correlated with RAGE mRNA, white blood cell counts, neutrophilcounts, lymphocyte counts, total cholesterol, low density lipoprotein andapolipoprotein B100(r=0.29,0.36,0.26,0.28,0.29; P<0.05),while negativelycorrelated with high density lipoprotein (r=-0.30;P <0.01); the level ofPBMCs RAGE mRNA was positively correlated with Lymphocyte counts,total cholesterol and apolipoprotein B100(r=0.35,0.35,0.44; P<0.05).Conclusion: HMGB1and its signaling pathway may play an importantrole in the pathogenesis of gouty arthritis, which may also be involved inregulating the lipid metabolism of gout.