[1]李媛 陈达 余阗△ 彭力平 胡烈奎 廖州伟 马笃军.六味骨痹汤对兔骨关节炎软骨的修复作用及其机制初探[J].中国中医骨伤科杂志,2018,26(09):9-13,18.
 LI Yuan CHEN Da YU Tian PENG Liping HU Liekui LIAO Zhouwei MA Dujun.Effect and Mechanism of Liuweigubi Decoction on Osteoarthritis Cartilage in Rabbits[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2018,26(09):9-13,18.
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六味骨痹汤对兔骨关节炎软骨的修复作用及其机制初探()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第26卷
期数:
2018年09期
页码:
9-13,18
栏目:
实验研究
出版日期:
2018-09-06

文章信息/Info

Title:
Effect and Mechanism of Liuweigubi Decoction on Osteoarthritis Cartilage in Rabbits
文章编号:
1005-0205(2018)09-0009-05
作者:
李媛1 陈达2 余阗3△ 彭力平3 胡烈奎1 廖州伟3 马笃军3
1广州中医药大学第四临床医学院(广东 深圳,518033) 2深圳宝安中医院(集团)骨伤科一区 3深圳市中医院骨伤科一病区
Author(s):
LI Yuan1 CHEN Da2 YU Tian3△ PENG Liping3 HU Liekui1 LIAO Zhouwei3 MA Dujun3
1Fourth Clinical Medical College,Affiliated to Guangzhou University of Traditional Chinese Medicine,Shenzhen 518033,Guangdong China; 2Baoan Hospital of Traditional Chinese Medicine,Shenzhen 518101,Guangdong China; 3Shenzhen Hospital of Traditional Chinese Medicine,Shenzhen 518033,Guangdong China.
关键词:
六味骨痹汤 骨关节炎 关节软骨修复 Ⅱ型胶原蛋白
Keywords:
Keywords: Liuweigubi decoction osteoarthritis rabbit articular cartilage repair type Ⅱ collagen
分类号:
R-33
文献标志码:
A
摘要:
目的:观察六味骨痹汤对兔骨关节炎模型关节软骨形态、Ⅱ型胶原蛋白表达及体液中胶原酶3(MMP-13)、肿瘤坏死因子-α(TNF-α)、软骨寡聚基质蛋白(COMP)的影响,探讨其对骨关节炎(OA)软骨的修复作用及其可能机制。方法:取2~3月龄清洁级新西兰兔32只,体质量(2.42±0.23)kg,采用木瓜蛋白酶关节注射法建立兔OA模型,随机区组法分为六味骨痹汤组、硫酸氨基葡萄糖(GS)组和模型组,另设正常组。前两组分别予六味骨痹汤3.83 g/(kg·d)、硫酸氨基葡萄糖胶囊77 mg/(kg·d)溶于生理盐水10 mL灌胃,模型组和正常组均予生理盐水(10 mL/d)灌胃。6周后采用酶联免疫吸附法(ELISA)检测血清及关节液中MMP-13,TNF-α及COMP的含量; 处死实验兔,按Pelletier原则对关节软骨大体形态评分; 取软骨病理标本,部分予苏木精-伊红染色后用改良Mankin's法予组织形态学观察评分,其他标本免疫组化染色后对其Ⅱ型胶原蛋白表达情况进行观察评分。结果:与模型组相比,六味骨痹汤组血清和关节液中MMP-13,TNF-α及COMP的含量降低,差异有统计学意义(P<0.05); 关节软骨Pelletier 评分和改良Mankin's 评分显著降低,差异有统计学意义(P<0.05); Ⅱ型胶原蛋白表达有所增加,差异有统计学意义(P<0.05).与GS组相比,上述指标差异均无统计学意义(P>0.05).结论:六味骨痹汤可促进兔OA模型软骨修复,其机制可能是通过降低兔血清和关节液中MMP-13,TNF-α等因子的含量抑制软骨破坏,从而提高Ⅱ型胶原蛋白的表达来发挥作用。
Abstract:
Abstract Objective:To observe the morphology of articular cartilage,the expression of type Ⅱ collagen and the collagenase 3(MMP-13),tumor necrosis factor-α(TNF-α)and cartilage oligomeric matrix protein(COMP)in rabbit osteoarthritis model and explore the effect of Liuweigubi Decoction on osteoarthrosis(OA)cartilage and its possible mechanism in rabbits with osteoarthritis.Methods:Thirty-two clean-grade New Zealand rabbits aged 2 to 3 months were used and the body weight was(2.42±0.23)kg.Rabbit OA models which established by papain joint injection were randomly divided into Liuweigubi decoction(LD)group,glucosamine sulfate(GS)group and model group.In addition,normal group was set up separately.The first two groups were respectively treated with Liuweigubi decoction 3.83 g/(kg·d)and glucosamine sulfate capsules 77 mg/(kg·d)which were dissolved in 10 mL normal saline.Normal group and model group received normal saline 10(mL/d)gavage.After 6 weeks,serum MMP-13,TNF-α,and COMP levels in serum and joint fluid were measured by enzyme-linked immunosorbent assay(ELISA).Rabbits were sacrificed,and general articular cartilage morphology was scored according to the Pelletier principle.Cartilage pathological specimens were taken,and after hematoxylin-eosin staining,histomorphological observations were performed using improved Mankin's method.The expression of type Ⅱ collagen was observed in other specimens after immunohistochemical staining.Results:Compared with the model group,the levels of MMP-13,TNF-α and COMP in the serum and synovial fluid of the Liuweigubi decoction group decreased(P<0.05),and the Pelletier score and improved Mankin's score of the articular cartilage decreased significantly(P<0.05).The expression of type Ⅱ collagen was increased(P<0.05).There was no statistically significant difference between the above parameters compared with GS group(P>0.05).Conclusion:Liuweigubi decoction can promote the repair of OA model cartilage in rabbits.The mechanism may be to reduce cartilage destruction by decreasing the content of MMP-13,TNF-α and other factors in rabbit serum and synovial fluid,so as to increase the expression of type Ⅱ collagen.

参考文献/References:

[1] Fransen M,Bridgett L,March L,et al.The epidemiology of osteoarthritis in Asia[J].International Journal of Rheumatic Diseases,2011,14(2):113-1121.
[2] 陈达,彭力平,余阗,等.“六味骨痹汤”治疗膝骨关节炎疗效及安全性的临床研究[J].中国中医骨伤科杂志,2017,25(5):26-29.
[3] 卫彦强,石继祥,纪斌,等.骨性关节炎发病机制的研究进展[J].医学综述,2018,24(5):838-842.
[4] 王晶,董芳芳,李晓锋,等.益气化瘀方减轻HIF-1α条件性基因敲除小鼠膝关节软骨退变的研究[J].中国骨伤,2013,26(6):486-492.
[5] 晏丹.关节软骨生化结构及其与力学性能关系研究进展[J].上海交通大学学报:医学版,2009,29(3):341-346.
[6] 蒋萍,蔚芃,赵明才,等.Ⅰ、Ⅱ型胶原蛋白对人软骨细胞生物学特性的影响[J].中国临床康复,2014,18(30):4845-4850.
[7] Horiuchi K.A brief history of tumor necrosis factor α-converting enzyme:an overview of ectodomain shedding[J].Keio Journal of Medicine,2013,62(1):29-30.
[8] 刘奋飞.滑液尿酸、血清及滑液 IL-1β、IL-6、TNF-α水平与膝骨关节炎的相关性[J].中国卫生工程学,2017,16(3):367-370.
[9] 乔长峰,杨开舜.MMP-13、TIMP-1在兔骨关节炎模型的表达及其意义[J].中国现代医生,2009,47(3):39-41.
[10] 祁雷,姚运峰,荆珏华.基质金属蛋白酶抑制剂在骨关节炎治疗中应用的研究进展[J].齐鲁医学杂志,2017,32(1):111-114.
[11] 刘志伟,严伟洪,孙晓亮,等.软骨代谢标志物COMP对骨关节炎软骨改变的反应[J].实用骨科杂志,2007,13(8):469-471.
[12] Larsson E,Erlandsson HH,Larsson A,et al.Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP[J].Rheumatology(Oxford),2004,43(4):428-434.
[13] 李具宝,张磊,屈尚可,等.膝骨关节炎近10年文献中内服方药功效和中医证型分析[J].中国中医骨伤科杂志,2014,22(3):20-21.
[14] 张璇,肖玉梅,王茹,等.淫羊藿苷对胶原支架中软骨细胞生长及胞外基质分泌的影响[J].中药药理与临床,2010,26(6):25-27.
[15] 鲍远.淫羊藿苷促进关节软骨细胞增殖和表型维持及相关机制研究[D].武汉:华中科技大学,2016.
[16] 高堪达.淫羊藿苷对骨关节炎小鼠软骨下骨的保护作用及其机制研究[D].南京:南京医科大学,2016.
[17] 郑婧,张贵君,韦敏,等.五加皮药材基原、化学成分及药理作用研究进展[J].辽宁中医药大学学报,2015,17(8):104-107.
[18] 陈泽华.龟甲胶、鹿角胶含药血清对豚鼠关节软骨细胞活性的影响[D].福州:福建中医药大学,2016.
[19] 金连峰.单味中药骨碎补对兔膝骨关节炎软骨细胞凋亡作用的实验研究[J].中华中医药学刊,2013,31(7):1699-1703.
[20] 陈达,廖州伟,马笃军,等.牛膝醇提物对兔骨关节炎模型的疗效比较[J].中国医药导报,2016,13(25):21-24.

备注/Memo

备注/Memo:
基金项目:广东省中医药局科研项目(20171245) 通信作者 E-mail:yutianmail@hotmail.com
更新日期/Last Update: 2018-09-06