[1]程增玉,姜雯,徐浩东,等.基于核因子-κB受体活化因子受体/骨保护素探讨复方雷公藤外敷剂改善Ⅱ型胶原诱导型关节炎模型大鼠骨破坏[J].中国中医骨伤科杂志,2023,31(02):12-17+23.
 CHENG Zengyu JIANG Wen XU Haodong LI Da WANG Yiran TANG Xiaopo.Study on Compound Tripterygium Wilfordii External Application on the Improvement of Bone Destruction in Rats with Collagen-Induced Arthritis Based on RANKL/OPG[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2023,31(02):12-17+23.
点击复制

基于核因子-κB受体活化因子受体/骨保护素探讨复方雷公藤外敷剂改善Ⅱ型胶原诱导型关节炎模型大鼠骨破坏()
分享到:

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第31卷
期数:
2023年02期
页码:
12-17+23
栏目:
实验研究
出版日期:
2023-02-15

文章信息/Info

Title:
Study on Compound Tripterygium Wilfordii External Application on the Improvement of Bone Destruction in Rats with Collagen-Induced Arthritis Based on RANKL/OPG
文章编号:
1005-0205(2023)02-0012-06
作者:
程增玉1姜雯1徐浩东2李达1王一燃1唐晓颇1△
1中国中医科学院广安门医院(北京,100053) 2南京中医药大学附属苏州市中医医院
Author(s):
CHENG Zengyu1 JIANG Wen1 XU Haodong2 LI Da1 WANG Yiran1 TANG Xiaopo1△
1Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China; 2Suzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Suzhou 215003, Jiangsu China.
关键词:
类风湿关节炎 胶原诱导型关节炎 雷公藤 外治 核因子-κB受体活化因子受体 骨保护素
Keywords:
rheumatoid arthritis collagen-induced arthritis tripterygium wilfordii external treatment nuclear factor-κB receptor activating factor ligand osteoprotegerin
分类号:
R-33
文献标志码:
A
摘要:
目的:观察复方雷公藤外敷剂对Ⅱ型胶原诱导型关节炎模型大鼠的骨形态学影响,探讨其可能的作用机制。方法:将50只雌性SD大鼠随机分为正常组(NOR组)、模型组(CIA组)、复方雷公藤外敷剂组(TWE组)、雷公藤多苷组(TWG组)、扶他林乳胶剂组(VOT组),每组10只。除NOR组外,对其余大鼠进行尾根部皮下注射Ⅱ型胶原诱导,7 d后加强免疫造模。TWE组以0.60 g/(kg·d)外用、TWG组6.25 mg/(kg·d)灌胃、VOT组乳胶剂0.016 mL/(kg·d)外用,NOR组与CIA组以生理盐水涂抹膝踝关节,连续给药28 d。观察大鼠一般状态、双下肢肿胀程度; 观察各组膝、踝关节病理形态,借助微型计算机断层扫描(micro-CT)观察骨质改变,采用酶联免疫吸附法(ELISA)测定、蛋白免疫印迹法(Western Blot)观察外周血及组织骨破坏与骨保护相关因子与蛋白表达。结果:与NOR组比较,CIA组一般状态不佳,关节炎评分与足趾容积均显著增高,micro-CT显示踝关节、跖趾关节破坏严重,血清MMP1、MMP13、RANKL显著增高,滑膜组织中RANKL/OPG显著升高。与CIA组相比,各治疗组随着给药时间的增加,关节炎评分与足趾容积均有下降,micro-CT显示踝关节、跖趾关节骨表面积/骨体积比值低于模型组,差异有统计学意义(P<0.05),其中TWE组与VOT组改善最为明显,差异有统计学意义(P<0.01); 各治疗组血清MMP1、MMP13、RANKL、关节组织中RANKL/OPG均低于CIA组。结论:复方雷公藤外敷剂能够改善模型大鼠关节骨破坏,其作用机制可能与降低MMP1、MMP13、RANKL水平,抑制RANKL/OPG,调控骨平衡有关。
Abstract:
Objective:To observe the efficacy of compound tripterygium wilfordii external application on bone morphology of rats with type Ⅱ collagen-induced arthritis and to explore its possible mechanism. Methods:50 female SD rats were randomly divided into normal group(NOR group), model group(CIA group), compound tripterygium wilfordii external application group(TWE group), tripterygium wilfordii glycosides group(TWG group)and voltaren cream group(VOT group)with 10 rats in each group. Except for the NOR group, rats in the other groups were induced by subcutaneous injection of type Ⅱ collagen into the tail root, and strengthened immune after 7 d. The rats in the TWE group(0.60 g/(kg·d)), TWG group(6.25 mg/(kg·d))and VOT group(latex 0.016 mL/(kg·d))were treated for 28 d, while the CON group and CIA group coated knee and ankle joint with normal saline for 28 d. The general state and the swelling degree of both lower limbs of rats were observed, the bone changes were observed by microcomputer tomography(micro-CT), and the expression of bone protection related factors and proteins in peripheral blood and tissue were observed by enzyme linked immunosorbent assay(ELISA)and Western Blot. Results:Compared with NOR group, the general condition of CIA group was poor, the arthritis index and toe volume were significantly increased, micro-CT showed that ankle joint and metatarsophalangeal joint were seriously damaged, the MMP1, MMP13, RANKL in serum and the RANKL/OPG in synovium were significantly increased. Compared with the CIA group, the arthritis index and toe volume of each treatment group decreased with the increase of administration time, and micro-CT showed that the bone surface area / bone volume ratio of ankle joint and metatarsophalangeal joint was lower than that of the CIA group(P<0.05), especially in TWE group and VOT group is obvious(P<0.05). The serum MMP1, MMP13, RANKL and RANKL/OPG in joint tissue in each treatment group were lower than those in CIA group. Conclusion:Compound tripterygium wilfordii external application can effectively improve the destruction of articular bone in CIA rats, and its mechanism may be related to reducing the levels of MMP1, MMP13 and RANKL, inhibiting RANKL/OPG and regulating bone balance.

参考文献/References:

[1] 田新平,李梦涛,曾小峰.我国类风湿关节炎诊治现状与挑战:来自中国类风湿关节炎2019年年度报告[J].中华内科杂志,2021,60(7):593-598.
[2] SMOLEN J S,ALETAHA D,MCINNES I B.Rheumatoid arthritis[J].Lancet,2016,388(10055):2023-2038.
[3] 耿研,谢希,王昱,等.类风湿关节炎诊疗规范[J].中华内科杂志,2022,61(1):51-59.
[4] 周云杉,王秀茹,安媛,等.全国多中心类风湿关节炎患者残疾及功能受限情况的调查[J].中华风湿病学杂志,2013,17(8):526-532.
[5] LIU J J,LI R,GAN Y Z,et al.Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis[J].Chinese Med J,2019,132(9):1009-1014.
[6] WANG G Y,ZHANG S L,WANG X R,et al.Remission of rheumatoid arthritis and potential determinants:a national multi-center cross-sectional survey[J].Clin Rheumatol,2015,34(2):221-230.
[7] ALTEN R,MISCHKEWITZ M.2021 ACR guideline reflects changes in RA treatment[J].Nat Rev Rheumatol,2021,17(9):513-514.
[8] 巩勋,崔家康,姜泉,等.1 388例类风湿关节炎患者中医证型与疾病活动度特征横断面调查[J].中医杂志,2021,62(4):312-317.
[9] 刘蔚翔,姜泉.类风湿关节炎“湿、热、瘀”病机理论探析[J].中医杂志,2020,61(24):2148-2153.
[10] 刘蔚翔,姜泉.见骨损而非独责之于肾[J].中医杂志,2019,60(14):1198-1201.
[11] 杜羽,王雷,罗成贵,等.清热活血方药治疗类风湿关节炎3年期放射学评价研究[J].世界中西医结合杂志,2018,13(11):1577-1580.
[12] 李光耀,唐晓颇,姜泉,等.清热活血方药治疗类风湿关节炎骨破坏5年期放射学观察[J].世界中西医结合杂志,2019,14(4):516-520.
[13] 焦娟,姜泉.复方雷公藤外敷降低类风湿关节炎疾病活动度的研究[J].中国中西医结合杂志,2012,32(11):1470-1472.
[14] 曹炜,焦娟,姜泉.复方雷公藤外敷治疗活动期类风湿关节炎的临床疗效观察[J].中华中医药杂志,2007,22(7):433-435.
[15] 焦娟,唐晓颇,员晶,等.复方雷公藤外敷剂对类风湿关节炎患者关节疼痛的影响[J].中国中西医结合杂志,2016,36(1):29-34.
[16] 赵越,唐晓颇,姜泉,等.复方雷公藤外敷对Ⅱ型胶原诱导型关节炎大鼠滑膜组织细胞因子及ERK通路的影响[J].中医杂志,2017,58(7):582-586.
[17] 赵越,唐晓颇,姜泉,等.复方雷公藤外敷对CIA大鼠成纤维样滑膜细胞中细胞因子和ERK通路表达的影响[J].中华中医药杂志,2018,33(11):5155-5158.
[18] TRENTHAM D E,TOWNES A S,KANG A H.Autoimmunity to type Ⅱ collagen an experimental model of arthritis[J].J Exp Med,1977,146(3):857-868.
[19] ZHAO H,XU H,ZUO Z,et al.Yishen Juanbi pill ameliorates bone loss and destruction induced by arthritis through modulating the balance of cytokines released by different subpopulations of T cells[J].Front Pharmacol,2018,9:262.
[20] CANNON G W,MCCALL S,COLE B C,et al.Effects of indomethacin,cyclosporin,cyclophosphamide,and placebo on collagen-induced arthritis of mice[J].Agents Actions,1990,29(3/4):315-323.
[21] 夏晴,纪羽婷,刘海亮,等.类风湿关节炎动物模型研究进展[J].中国比较医学杂志,2020,30(11):107-113.
[22] KOMATSU N,TAKAYANAGI H.Mechanisms of joint destruction in rheumatoid arthritis-immune cell-fibroblast-bone interactions[J].Nat Rev Rheumatol,2022,18(7):415-429.
[23] BRIGHTWELL C R,LATHAM C M,THOMAS N T,et al.A glitch in the matrix:the pivotal role forextracellular matrix remodeling during muscle hypertrophy[J].Am J Physiol-Cell Ph,2022,323(3):C763-C771.
[24] ALAMGEER,HASAN U H,UTTRA A M,et al.Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis[J].Phytomedicine,2020,66:153134.
[25] BOYCE B F,XING L.Biology of RANK,RANKL,and osteoprotegerin[J].Arthritis Res Ther,2007,9(Suppl 1):S1.
[26] GALLAGHER J C.Advances in bone biology and new treatments for bone loss[J].Maturitas,2008,60(1):65-69.
[27] TSUKASAKI M,ASANO T,MURO R,et al.OPG production matters where it happened[J].Cell Rep,2020,32(10):108124.
[28] TANAKA S,TANAKA Y.RANKL as a therapeutic target of rheumatoid arthritis[J].J Bone Miner Metab,2021,39(1):106-112.
[29] HAIRUL-ISLAM M I,SARAVANAN S,THIRUGNANASAMBANTHAM K,et al.Swertiamarin,a natural steroid,prevent bone erosion by modulating RANKL/RANK/OPG signaling[J].Int Immunopharmacol,2017,53:114-124.
[30] 程增玉,徐浩东,姜雯,等.类风湿关节炎滑膜微环境的中医属性及治则探讨[J].现代中西医结合杂志,2022,31(6):843-847.
[31] 姜泉,蒋红,曹炜,等.475例类风湿关节炎患者中医临床证候分析[J].中医杂志,2007,48(3):253-255.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金面上项目(81873281)
中国中医科学院科技创新工程项目(CI2021A01502)
国家重点研发计划项目(2018YFC1705203)
中国中医科学院自主选题(ZZ15-XY-PT-11)
通信作者 E-mail:tangxiaopo@163.com
更新日期/Last Update: 2023-02-10