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中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (4): 383-388.doi: 10.12092/j.issn.1009-2501.2018.04.004

• 基础研究 • 上一篇    下一篇

染料木素调控JAK2/STAT3信号通路改善骨性关节炎大鼠软骨代谢的作用研究

胡 炯1,王伟东1,王昌兴1,董黎强1,刘启明2   

  1. 1 浙江中医药大学附属第二医院,杭州 310005,浙江;2 富阳中医骨伤医院,杭州 311400,浙江
  • 收稿日期:2018-01-10 修回日期:2018-02-28 出版日期:2018-04-26 发布日期:2018-04-13
  • 作者简介:胡炯,主治医师,硕士,研究方向:骨关节疾病基础研究及临床诊治。 Tel:13575483108 E-mail:yisheng198386912@163.com
  • 基金资助:

    浙江省医药卫生科技项目(2016KYA153)

Effect of genistein on cartilage mediated by JAK2/STAT3 signaling pathway in rats with osteoarthritis

HU Jiong1, WANG Weidong1, WANG Changxing1, DONG Liqiang1, LIU Qiming2   

  1. 1 Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China; 2 Fuyang Traditional Chinese Medicine Bone Fracture Hospital,Hangzhou 311400, Zhejiang, China
  • Received:2018-01-10 Revised:2018-02-28 Online:2018-04-26 Published:2018-04-13

摘要:

目的:在大鼠骨性关节炎(OA)模型中观察染料木素通过酪氨酸蛋白激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路对骨性关节炎软骨代谢的作用。方法:SD大鼠随机分为3组,相应处理6周后取材,采用组织学染色的方法观察软骨标本的组织学形态、ELISA检测大鼠关节液中TNF-α表达水平、Western blot检测关节软骨细胞中p-JAK2、p-STAT3、MMP-13、Bax、Bcl-2相关蛋白的表达。结果:染料木素能有效增加OA关节软骨的胶原及蛋白多糖含量,使软骨组织结构接近正常软骨。与OA组相比,染料木素+OA组的TNF-α表达显著下调(P<0.01),与正常组相近(P>0.05)。与OA组相比,染料木素+OA组的p-JAK2、p-STAT3及Bcl-2蛋白表达水平明显上升、MMP-13、Bax蛋白表达水平明显下降(均P<0.05)。结论:JAK2/STAT3信号通路与骨性关节炎软骨退变的病理过程密切相关,染料木素可激活JAK2/STAT3信号通路,抑制骨性关节炎炎症反应,抑制软骨细胞的凋亡,明显缓解关节软骨的退变,降低OA进展水平。

关键词: 骨性关节炎, 染料木素, JAK2/STAT3信号通路, 炎症反应, 细胞凋亡

Abstract:

AIM: To investigate the effect of genistein on cartilage and its relation to JAK2/ STAT3 signaling pathway in rats with osteoarthritis(OA). METHODS: SD rats were randomly divided into control group, OA group and genistein with OA group. After 6 weeks of treatment, the histological morphology of cartilage specimen was observed by Histologic staining; the expression of TNF-α in synovial fluid of rats was detected by ELISA and the expressions of p-JAK2, p-STAT3, MMP-13, Bax and Bcl-2 in articular chondrocytes were detected by Western blot. RESULTS: Genistein can effectively increase the content of collagen and proteoglycan in the OA articular cartilage, and make the cartilage structure close to the normal cartilage. Compared with OA group, the expression of TNF-α in genistein+OA group was significantly down regulated (P<0.01), compared with the normal group, there was no significant difference in TNF-α expression of OA+genistein (P>0.05). Compared with OA group, the expression level of p-JAK2, p-STAT3 and Bcl-2 protein in genistein+OA group increased significantly (P<0.05), and the expression level of MMP-13 and Bax decreased significantly (P<0.05). CONCLUSION: JAK2/STAT3 signaling pathway is closely related to the pathological process of cartilage degeneration in osteoarthritis. Genistein can activate JAK2 STAT3 signaling pathway, inhibit the inflammation of osteoarthritis and the apoptosis of chondrocytes and relieve the degeneration of articular cartilage as well as reduce the level of OA progress.

Key words: osteoarthritis, genistein, JAK2/STAT3 signaling pathway, inflammatory reaction, apoptosis

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