CAJ | 학술논문

目的通过研究高迁移率族蛋白(HMGB)1及Toll样受体(TLR)4在类风湿关节炎(RA)外周血单个核细胞(PBMC)和血清中的表达,探讨HMGB1的作用及其与疾病活动的关系.方法选取活动期RA患者38例和非活动期RA患者36例及健康对照组26名.采用反转录-聚合酶链反应(RT-PCR)方法检测PBMC中HMGB1 mRNA的表达,酶联免疫吸附试验(ELISA)检测血清中HMGBI蛋白的表达.采用流式细胞术分析PBMC上TLR4的表达.结果 ①活动期RA组PBMC中HMGB1 mRNA相对表达量和血清中HMGB1蛋白水平均高于健康对照组和非活动期RA患者[分别为2.63与0.71.0.93和(10.2±1.2)与(7.5+1.8),(8.3±1.8)ng/ml,P＜0.01.②活动期RA患者CD14+单核细胞和CD3+淋巴细胞上TLR4蛋白相对表达量高于非活动期和健康对照组(P＜0.05或P＜0.01),非活动期患者高于健康对照组(P＜0.05或P＜0.01).③血清中HMGB1蛋白水平与红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、关节压痛数、肿胀数及关节X线分期均呈正相关,亦与TLR4蛋白相对表达量呈正相关.结论 RA患者PBMC具有合成和分泌HMGB1蛋白的功能,并部分通过与TLR4结合激活炎症反应,加重骨质破坏.
목적 통과연구고천이솔족단백(HMGB)1급Toll양수체(TLR)4재류풍습관절염(RA)외주혈단개핵세포(PBMC)화혈청중적표체,탐토HMGB1적작용급기여질병활동적관계.방법 선취활동기RA환자38례화비활동기RA환자36례급건강대조조26명.채용반전록-취합매련반응(RT-PCR)방법검측PBMC중HMGB1 mRNA적표체,매련면역흡부시험(ELISA)검측혈청중HMGBI단백적표체.채용류식세포술분석PBMC상TLR4적표체.결과 ①활동기RA조PBMC중HMGB1 mRNA상대표체량화혈청중HMGB1단백수평균고우건강대조조화비활동기RA환자[분별위2.63여0.71.0.93화(10.2±1.2)여(7.5+1.8),(8.3±1.8)ng/ml,P＜0.01.②활동기RA환자CD14+단핵세포화CD3+림파세포상TLR4단백상대표체량고우비활동기화건강대조조(P＜0.05혹P＜0.01),비활동기환자고우건강대조조(P＜0.05혹P＜0.01).③혈청중HMGB1단백수평여홍세포침강솔(ESR)、C반응단백(CRP)、류풍습인자(RF)、관절압통수、종창수급관절X선분기균정정상관,역여TLR4단백상대표체량정정상관.결론 RA환자PBMC구유합성화분비HMGB1단백적공능,병부분통과여TLR4결합격활염증반응,가중골질파배.
Objective To investigate the effect and possible mechanism of high mobility group box (HMGB) 1 in the development and progress of rheumatoid arthritis.Methods PBMC and serum samples were obtained from 74 RA patients (38 in active stage and 36 in stable stage) and 26 healthy controls.The expression of HMGB1 mRNA and protein was detected by RT-PCR and ELISA.Flow cytometry analysis ( FCM ) was used to detect the expression of Toll-like receptor 4 on PBMC.Results ①The expression of HMGBI mRNA and protein in active RA patients was significantly higher than that in healthy controls and inactive RA patients [2.63 vs 0.71，0.93 and (10.2±1.2) vs (7.5±1.8)，(8.3±1.8) ng/ml，respectively](P＜0.01 ).② The relative expression of TLR4 protein on CD14+ monocytes and CD3+ lymphocytes in active RA patients was increased than that in inactive RA and healthy controls (P＜0.05 or P＜0.01 ).It was also higher in inactive RA than in healthy controls (P＜0.05 or P＜0.01 ).③ Level of HMGB1 protein in serum of RA patients was positively correlated with ESR，CRP，RF，the numbers of tender joints and swollen joints as well as radiographic changes.Conclusion HMGB1 can be synthesized and released by PBMC of active RA patients，and then bind to TLR4 of PBMC to promote inflammatory responses and bone erosion.