风湿定胶囊对类风湿关节炎大鼠滑膜组织JAK/STAT信号通路的影响Influence of Fengshiding Capsule on JAK/STAT Signal Pathway in Synovial Tissue of Rats with Rheumatoid Arthritis
陈勇,陈涛,高永翔
摘要(Abstract):
目的观察风湿定胶囊对类风湿性关节炎(RA)大鼠滑膜组织中JAK-STAT信号通路的影响。方法取85只大鼠,随机选出10只为空白组(予等量生理盐水),其余75只注射Ⅱ型胶原制备RA大鼠模型;将造模成功大鼠随机分为模型组(等量生理盐水)、阳性对照组[甲氨蝶呤0.5 mg/(kg·d)]、风湿定胶囊低剂量组[200 mg/(kg·d)]、中剂量组[400 mg/(kg·d)]、高剂量组[800 mg/(kg·d)];观察并记录给药后不同时间段大鼠体质量变化等一般情况及右后足肿胀体积;给药4周后,以免疫组化法观察各组大鼠滑膜组织病理变化,Western blotting测定各组大鼠关节滑膜组织中p-JAK3、p-STAT3的蛋白表达水平。结果模型组关节肿胀明显,摄食及活动减少,精神萎靡;给药治疗后,各治疗组大鼠摄食及精神状态较模型组明显改善,且随治疗时间延长,效果越明显;模型组大鼠体质量增加低于治疗组。治疗4周后,模型组及各治疗组大鼠足肿胀体积均显著高于空白组;随风湿定胶囊剂量的增加,肿胀体积逐渐减小(P<0.05),且中、高剂量组效果显著优于阳性对照组(P<0.05)。各组间JAK3蛋白及STAT3蛋白表达水平差异无统计学意义(P>0.05);模型组及各治疗组大鼠关节滑膜组织中p-JAK3、p-STAT3的蛋白表达水平均显著高于空白组(P<0.05);随风湿定胶囊剂量的增加,p-JAK3、p-STAT3的蛋白表达水平均逐渐下调(P<0.05),且中、高剂量组下调效果显著优于阳性对照组(P<0.05)。结论风湿定胶囊可能通过下调RA大鼠关节滑膜组织中p-JAK3、p-STAT3的表达调控JAK/STAT信号通路进行RA的治疗。
关键词(KeyWords): 类风湿性关节炎;风湿定胶囊;滑膜组织;JAK-STAT信号通路
基金项目(Foundation): 四川省卫生厅科研基金项目(150051)
作者(Author): 陈勇,陈涛,高永翔
参考文献(References):
- [1]徐艳明.痹祺胶囊对CIA大鼠IL-6及JAK-STAT信号通路的影响[D].重庆:重庆医科大学,2016.
- [2]张欣悦,高永翔.JAK-STAT信号通路与类风湿关节炎相关研究进展[J].实用中医药杂志,2016,32(2):196-198.
- [3]Isom覿ki P,Junttila I,Vidqvist KL,et al.The activity of JAKSTAT pathways in rheumatoid arthritis:constitutive activation of STAT3 correlates with interleukin 6 levels[J].Rheumatology,2015,54(6):1103-1113.
- [4]陈呢喃,张冬青.JAK-STAT信号通路在类风湿关节炎中的研究进展[J].现代免疫学,2013,33(5):425-428.
- [5]陈玉兴,卓俊城,黄雪君,等.痹痛消胶囊对大鼠类风湿性关节炎的作用及其机制[J].中成药,2016,38(6):1211-1215.
- [6]李颖,汪悦,覃仕化,等.类风湿性关节炎的研究进展[J].中国矫形外科杂志,2011,19(7):581-584.
- [7]胡长玲,林兵,郑承剑,等.抗类风湿性关节炎的天然药物及其作用机制研究进展[J].中草药,2011,42(7):1435-1440.
- [8]Yee A,Webb T,Seaman A,et al.Anti-Car P antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis[J].Immunologic Research,2015,61(1-2):24-30.
- [9]池里群,周彬,高文远,等.治疗类风湿性关节炎常用药物的研究进展[J].中国中药杂志,2014,39(15):2851-2858.
- [10]朱洁宜,吴鑫宇,周海纯,等.中医药治疗类风湿关节炎的研究进展[J].中医药信息,2015,32(1):115-117.
- [11]赵静.青藤碱对类风湿关节炎模型大鼠TLRs及JAKSTAT信号通路调控基因的影响[D].成都:成都中医药大学,2014.
- [12]潘志鹏,伦永志.JAK/STAT信号通路在机体免疫及相关疾病中的作用机制[J].中国免疫学杂志,2016,32(9):1395-1399.
- [13]张斌,钟德玝,王群伟,等.JAK/STAT信号通路与肝细胞性肝癌的肿瘤进展和预后的相关性研究[J].细胞与分子免疫学杂志,2010,26(4):368-370.
- [14]Priceman SJ,Deng J,Jove R,et al.Chapter 26-JAK/STAT signaling in myeloid cells:targets for cancer immunotherapy[J].Cancer Immunotherapy,2013:435-449.
- [15]Domanska D,Brzezianska E.Review:The JAK/STAT protein activation-role in cancer development and targeted therapy[J].Current Signal Transduction Thera py,2012,7(3):187-201.
- [16]Wang L,Li J,Li D.Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats by inhibiting JAK/STAT signaling pathway[J].International Journal of Clinical&Experimental Pathology,2015,8(1):466-473.
- [17]Alrasheed NM,Alrasheed NM,Hasan IH,et al.Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats[J].Drug Design Development&Therapy,2016,10(1):2095-2107.
- [18]Malemud CJ,Miller AH.Pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression drugs[J].Expert Opinion on Therapeutic Targets,2008,12(2):171-183.
- [19]Walker JG,Ahern MJ,Coleman M,et al.Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment[J].Annals of the Rheumatic Diseases,2007,65(12):1558-1564.
- [20]wierkot J,Nowak B,Czarny A,et al.The activity of JAK/STAT and NF-κB in patients with rheumatoid arthritis[J].Advances in Clinical&Experimental Medicine Official Organ Wroclaw Medical University,2016,25(4):709-717.