HMGB1与JAK2/STAT1信号通路在大鼠滑膜组织增殖中的相关性研究被引量：3

CORRELATION OF HMGB1 AND JAK2/STAT1 SIGNAL TRANSDUCTION PROCESS IN THE RAT MODEL OF COLLAGEN INDUCED ARTHRITIS

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摘要目的探讨胶原诱导的关节炎大鼠中高迁移率族蛋白(high mobility group box,HMGB)1对磷酸化janus激酶(phospho-jgnus kinase,P-JAK)2/信号转导及转录活化因子(signal transducer and activator oftranscription,P-STAT)1信号转导通路的调控作用。方法将Wistar大鼠随机分成4组,正常对照Ⅰ组、正常对照Ⅱ组、模型Ⅰ组和模型Ⅱ组。光镜下观察关节组织结构变化。免疫组织化学检测HMGB1、增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)蛋白表达,流式细胞术检测P-JAK2、P-STAT1和细胞因子信号传导抑制蛋白1(suppressor of cytokine signaling,SOCS1)蛋白的表达。结果模型组大鼠随病程延长滑膜组织增生、炎细胞浸润、骨破坏加重,细胞核、细胞浆以及细胞外基质中HMGB1蛋白表达显著增加,同时伴随PCNA蛋白表达增加;与正常对照组相比,模型Ⅰ组P-JAK2、P-STAT1和SOCS1蛋白表达显著增加(P<0.01);与模型Ⅰ组相比,模型Ⅱ组P-JAK2、SOCS1的表达量下降(P<0.05),P-STAT1的表达量变化差异无统计学意义(P>0.05)。P-STAT1与HMGB1、PCNA的表达呈正相关(r=0.474,P=0.014;r=0.529,P=0.005)。结论 HMGB1可能激活了JAK2/STAT1信号转导通路,启动了滑膜增殖和骨质破坏过程。 Objective To investigate the regulating effect of high mobility group box （HMGB） 1 on phospho - janus kinase2/signal transducer and activator of transcription 1 （ p - JAK2/STAT1 ） signal transduction process in the rat model of collagen induced arthritis （CIA）. Methods All 30 male Wistar rats were divided randomly into four groups, two control groups （each including 6 rats） and two model groups （ each including 9 rats）. Type Ⅱ collagen （Ⅱ） was prepared for establishing CIA models. HE staining was used to observe the pathological changes of rat joint structure. The expression of HMGB1 and proliferation cell nuclear antigen （PCNA） proteins in synovium and articular tissues were analyzed by immunohistochemistry（IHC）. Flow cytometric analysis （FCM） was performed to detect the expression of p - JAK2, p - STAT1, suppressor of cytokine signaling （SOCS） 1 proteins of articular tissues. Results Specimens from model groups displayed a strong destruction with synoviocyte proliferation, inflammatory cells infiltration, even accompanied by cartilage or bone erosion. IHC staining revealed that HMGB1 protein expression significantly increased in the nuclei, cytoplasm and extracellular matrix, and positive expression ceils of PCNA increased too. Compared with normal control group, p - JAK2, p - STAT1, SOCS1 protein expression markedly increased in model group Ⅰ （P 〈 0.01 ）. But compared with in model group Ⅰ , the expression of p -JAK2 and SOCS1 decreased, p -STAT1 protein had no statistical change in model group Ⅱ. There were positive correlation between p - STAT1 and HMGB1, PCNA proteins expression（r=0.474,P=0. 014;r=0. 529,P=0. 005）. Conclusion HMGB1 plays an important role in promoting synovicytes proliferation and bone destruction of CIA rats by activating JAK2/STAT1 signal transduction process.

作者张明峰周守勤白连祥郭惠芳高丽霞马丽艳

机构地区河北医科大学第二医院免疫风湿科唐山钢铁集团有限公司医院检验科河北省承德市第五医院老年病科

出处《河北医科大学学报》 CAS 2011年第7期750-754,共5页 Journal of Hebei Medical University

基金河北省科技厅科技攻关基金资助项目(08206122D)

关键词关节炎胶原大鼠 arthritis collagen rats

分类号 R361.3 [医药卫生—病理学]

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参考文献11

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