清痹片对类风湿关节炎KLF6-FRP调控体系的干预作用  

The effect of Qingbi Tablet on the KLF6-FRP regulation system of rheumatoid arthritis process

作　　者：刘维[1] 吴沅皞[2] 刘晓亚[1] 张磊[1] 薛斌[2] 陈英俊[2] 

机构地区：[1]天津中医药大学第一附属医院风湿免疫科,天津300193 [2]天津中医药大学研究生院,天津300193

出　　处：《中华中医药杂志》2011年第12期2862-2865,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.30772809)~~

摘　　要：目的:探讨清痹片对KLF6-FRP调控体系的干预作用,为中医药治疗类风湿关节炎(RA)的机制研究和推广应用提供依据。方法:复制胶原诱导型关节炎(CIA)大鼠模型,随机分为空白组,模型组,清痹片低剂量组、中剂量组、高剂量组,并以甲氨蝶呤(MTX)治疗组作为阳性对照,致炎第21天起每天给药干预。分别于第35天和第49天各处死一半动物,取腕关节行免疫印迹法检测Kruppel样转录因子6(KLF6)、卵泡抑素相关蛋白(FRP),踝关节行免疫组化法实验检测转化生长因子β1(TGFβ1)、肿瘤坏死因子α(TNFα)、白细胞介素1β(IL-1β)、基质金属蛋白酶3(MMP-3),比较各组间各炎性蛋白表达的差异。结果:成功复制CIA模型,模型组KLF6、FRP、TGFβ1、TNFα、IL-1β、MMP-3蛋白表达水平较空白组升高(P<0.01);清痹片中、高剂量组KLF6蛋白表达水平与模型组相比较低而FRP较高(P<0.01),并显示出一定的量效依赖关系;清痹片中、高剂量组FRP蛋白表达水平与MTX组相比较高(P<0.01);清痹片各剂量组、MTX组TGFβ1、TNFα、IL-1β、MMP-3表达水平均低于模型组;清痹片高剂量组TNFα、IL-1β、MMP-3表达水平低于MTX组(P<0.01)。结论:清痹片可能通过提高TGFβ1的下游产物FRP表达水平以及直接或间接抑制KLF6及其下游靶基因TGFβ1、炎性细胞因子IL-1β、TNFα和MMP-3等炎症介质的基因表达,从而干预KLF6-FRP调控体系,控制相关因子对RA病变过程的影响。Objective： The project intends to investigate the role of KLF6-FRP regulation system of rheumatoid arthritis process,then to illuminate the possible ati-arthritis mechanism of the Qingbi Tablet,as a scientific basis for the research and application of the antiarthritic traditional Chinese medicine.Methods： Focusing on the Qingbi tablet with the formulating principle of dispelling toxins and dredging collaterals,under the guidance of TCM theory,the experimental research used collagen-induced arthritis（CIA） as the experimental animal models with the incisiveness point of the KLF6-TGFβ1-FRP network（Kruppel like transcription factor 6-Transforming growth factor β1-Follistatin related protein）.Comparating with normal group,the CIA rats were divided randomly into 5 groups,treating with or without the Qingbi tablets of low,middle,high dosage（0.36g·kg-1·d-1,1g·kg-1·d-1 or 1.8g·kg-1·d-1） or Methotrexate.One half of rats were sacrificed on the 35th or the 49th day.The wrist joints were collected for measuring the KLF6 and FRP by Western Blotting.And the ankle joints were collected for measuring the TGFβ1,TNFα,IL-1β and MMP-3 with the immunohistochemistry assay.Results： The expression levels of KLF6,FRP,TGFβ1,TNFα,IL-1β,MMP-3 of CIA in rats were higher significantly compared with the normal ones（P0.01）.With a dose dependent,the expressions of KLF6 in the rats treating with Qingbi tablets of 1g·kg-1·d-1 or 1.8g·kg-1·d-1 were lower significantly compared with the model group but of FRP are higher（P0.01）.The expression levels of TGFβ1,TNFα,IL-1β,MMP-3 in treated groups are significantly lower than the model group（P0.01）.The expression levels of TNFα,IL-1β,MMP-3 of Qingbi high dosage group were power than the MTX group（P0.01）.Conclusion： The Qingbi Tablet has the effects of intervening the expression the KLF6-FRP regulation system and related factors on the RA process effectively.

关 键 词：清痹片 解毒通络法 类风湿关节炎 胶原诱导型关节炎 Kruppel样转录因子6-卵泡抑素相关蛋白调控体系 

分 类 号：R285.5[医药卫生—中药学]