中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2010年
8期
538-542
,共5页
李媛媛%李成荣%王国兵%杨军%贾实磊
李媛媛%李成榮%王國兵%楊軍%賈實磊
리원원%리성영%왕국병%양군%가실뢰
紫癜,过敏性%Toll样受体%聚合酶链反应
紫癜,過敏性%Toll樣受體%聚閤酶鏈反應
자전,과민성%Toll양수체%취합매련반응
Purpura,Schonlein-Henoch%Toll-like receptors%Polymerase chain reactive
目的 探讨Toll样受体(TLRs)信号途径异常活化在过敏性紫癜(HSP)免疫发病机制中的可能作用.方法 采用反转录-聚合酶链反应(RT-PCR)及实时荧光定量PCR检测外周血单个核细胞TLRs(1～10)及信号途径分子MyD88、TRAF6、TRIF,细胞因子/趋化因子干扰素(IFN)-α、IFN-β、白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α、干扰素诱导蛋白(IP)-10、活化正常T细胞表达和分泌的调节因子(RANTES)、诱导性一氧化氮合酶(iNOS)及Blys/April mRNA的表达;应用酶联免疫吸附试验(ELISA)检测Blys、IFN-α、IFN-β、IL-6、IL-1β、TNF-α血浆水平;采用t检验比较2组间差异.结果 ①HSP患儿TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9 mRNA表达高于健康对照组(P＜0.01),TLR4较健康对照组差异无统计学意义(P＞0.05);②TLRs信号途径相关分子MyD88(2.47±1.06)与(0.73±0.22)、TRAF6(2.54±0.72)×10-3与(0.70±0.20)×10-3、TRIF(3.18±0.86)×10-3与(0.93±0.35)×10-3较健康对照组明显升高(P＜0.01);③IFN-α、IFN-β mRNA及蛋白表达明显高于健康对照组(P＜0.01);④细胞因子/趋化因子IL-6、IL-1β、IP-10、RANTES、iNOS表达高于健康对照组(P＜0.01),TNF～α表达较健康对照组差异无统计学意义(P＞0.05);⑤HSP患儿Blys/April表达明显升高(P＜0.01).结论 HSP患儿TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9及其信号途径相关分子MyD88、TRAF6、TRIF明显升高,提示各种病原微生物触发TLRs过度活化可能是导致HSP免疫功能紊乱的始动因素之一,TLRs过表达所致的炎症细胞因子/趋化因子或Blys/April异常产生可能参与HSP免疫发病机制.
目的 探討Toll樣受體(TLRs)信號途徑異常活化在過敏性紫癜(HSP)免疫髮病機製中的可能作用.方法 採用反轉錄-聚閤酶鏈反應(RT-PCR)及實時熒光定量PCR檢測外週血單箇覈細胞TLRs(1～10)及信號途徑分子MyD88、TRAF6、TRIF,細胞因子/趨化因子榦擾素(IFN)-α、IFN-β、白細胞介素(IL)-6、IL-1β、腫瘤壞死因子(TNF)-α、榦擾素誘導蛋白(IP)-10、活化正常T細胞錶達和分泌的調節因子(RANTES)、誘導性一氧化氮閤酶(iNOS)及Blys/April mRNA的錶達;應用酶聯免疫吸附試驗(ELISA)檢測Blys、IFN-α、IFN-β、IL-6、IL-1β、TNF-α血漿水平;採用t檢驗比較2組間差異.結果 ①HSP患兒TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9 mRNA錶達高于健康對照組(P＜0.01),TLR4較健康對照組差異無統計學意義(P＞0.05);②TLRs信號途徑相關分子MyD88(2.47±1.06)與(0.73±0.22)、TRAF6(2.54±0.72)×10-3與(0.70±0.20)×10-3、TRIF(3.18±0.86)×10-3與(0.93±0.35)×10-3較健康對照組明顯升高(P＜0.01);③IFN-α、IFN-β mRNA及蛋白錶達明顯高于健康對照組(P＜0.01);④細胞因子/趨化因子IL-6、IL-1β、IP-10、RANTES、iNOS錶達高于健康對照組(P＜0.01),TNF～α錶達較健康對照組差異無統計學意義(P＞0.05);⑤HSP患兒Blys/April錶達明顯升高(P＜0.01).結論 HSP患兒TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9及其信號途徑相關分子MyD88、TRAF6、TRIF明顯升高,提示各種病原微生物觸髮TLRs過度活化可能是導緻HSP免疫功能紊亂的始動因素之一,TLRs過錶達所緻的炎癥細胞因子/趨化因子或Blys/April異常產生可能參與HSP免疫髮病機製.
목적 탐토Toll양수체(TLRs)신호도경이상활화재과민성자전(HSP)면역발병궤제중적가능작용.방법 채용반전록-취합매련반응(RT-PCR)급실시형광정량PCR검측외주혈단개핵세포TLRs(1～10)급신호도경분자MyD88、TRAF6、TRIF,세포인자/추화인자간우소(IFN)-α、IFN-β、백세포개소(IL)-6、IL-1β、종류배사인자(TNF)-α、간우소유도단백(IP)-10、활화정상T세포표체화분비적조절인자(RANTES)、유도성일양화담합매(iNOS)급Blys/April mRNA적표체;응용매련면역흡부시험(ELISA)검측Blys、IFN-α、IFN-β、IL-6、IL-1β、TNF-α혈장수평;채용t검험비교2조간차이.결과 ①HSP환인TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9 mRNA표체고우건강대조조(P＜0.01),TLR4교건강대조조차이무통계학의의(P＞0.05);②TLRs신호도경상관분자MyD88(2.47±1.06)여(0.73±0.22)、TRAF6(2.54±0.72)×10-3여(0.70±0.20)×10-3、TRIF(3.18±0.86)×10-3여(0.93±0.35)×10-3교건강대조조명현승고(P＜0.01);③IFN-α、IFN-β mRNA급단백표체명현고우건강대조조(P＜0.01);④세포인자/추화인자IL-6、IL-1β、IP-10、RANTES、iNOS표체고우건강대조조(P＜0.01),TNF～α표체교건강대조조차이무통계학의의(P＞0.05);⑤HSP환인Blys/April표체명현승고(P＜0.01).결론 HSP환인TLR1、TLR2、TLR6、TLR5、TLR3、TLR7、TLR9급기신호도경상관분자MyD88、TRAF6、TRIF명현승고,제시각충병원미생물촉발TLRs과도활화가능시도치HSP면역공능문란적시동인소지일,TLRs과표체소치적염증세포인자/추화인자혹Blys/April이상산생가능삼여HSP면역발병궤제.
Objective To investigate the role of signal transduction of TLRs in the Henoch-Schonlein purpura (HSP). Methods Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs(1～10), MyD88, TRAF6, TRIF, IFN-α, IFN-β, IL-6, IL-1β, TNF-α, IP-10, RANTES,iNOS, Blys/April mRNA expression in peripheral blood mononuclear cells and their expression levels were compared using t test., while the concentration of plasma cytokines such as Blys、IFN-α、IFN-β、IL-6、IL-1、TNF-α was measured by enzyme-linked immunosorbent assay(ELISA).Expression levels of those genes were compared using t test. Results①Compared with the control group, the expression levels of TLR1, TLR2,TLR6, TLR5, TLR3, TLR7, TLR9 mRNA were up-regulated significantly(P＜0.01), while no difference of TLR4 was detected (P＞0.05).②Transcription levels of MyDg8(2.47±1.06) vs(0.73±0.22), TRAF6 (2.54±0.72)×10-3vs(0.70±0.20)×10-3, TRIF(3.18±0.86)×10-3vs(0.93±0.35)×10-3 were significantly up-regulated in acute phase of HSP (P＜0.01).③The levels of IFN-α and IFN-β protein and mRNA were remarkable increased (P＜0.01).④ The expression of cytokine/chemotactic factor such as IL-6, IL-1β, IP-10, RANTES,iNOS was higher than that of the control group(p＜0.01), while TNF-αdid not change in children with HSP (P＞0.05). ⑤ It was detected that the expression of Blys/April was higher than that of the control group(P＜0.01). Conclusion Expressions of TLR1, TLR2, TLR6, TIR5, TLR3, TLR7, TLR9, MyD88, TRAF6,
and TRIF are up-regulated during acute phase of HSP, suggesting that aberrant activation of TLRs triggered by microbes may be one of the initiating factors of immune aberrance in HSP. Over expression of cytokine/chemotactic factor or Blys/April owning to the aberrant activation of TLRs, may be correlated with immunological pathogenesis of HSP.
