[1]郑文伟,翁霞萍,黄绥心,等.独活寄生汤对骨关节炎软骨退变的影响及其作用机制[J].中医正骨,2017,29(07):5-11.
　ZHENG Wenwei,WENG Xiaping,HUANG Suixin,et al.Effects of Duhuo Jisheng Tang on cartilage degeneration in the process of osteoarthritis and the mechanism of action[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2017,29(07):5-11.
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独活寄生汤对骨关节炎软骨退变的影响及其作用机制 ()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第29卷
期数:
2017年07期
页码:
5-11
栏目:
基础研究
出版日期:
2017-07-20

文章信息/Info

Title:
Effects of Duhuo Jisheng Tang on cartilage degeneration in the process of osteoarthritis and the mechanism of action
作者:
郑文伟1; 翁霞萍1; 黄绥心2; 郑春松1; 叶锦霞1; 吴追乐2; 许惠凤2; 吴明霞2; 李西海1; 刘献祥1
1.福建中医药大学,福建 福州 350122; 2.福建省中西医结合老年性疾病重点实验室,福建 福州 350122
Author(s):
ZHENG Wenwei1; WENG Xiaping1; HUANG Suixin2; ZHENG Chunsong1; YE Jinxia1; WU Zhuile2; XU Huifeng2; WU Mingxia2; LI Xihai1; LIU Xianxiang1
1.Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China 2.Fujian Key Laboratory of Integrated Medicine on Geriatrics,Fuzhou 350122,Fujian,China
关键词:
骨关节炎;  独活寄生汤;  软骨退变;  G蛋白偶联信号通路;  动物实验
Keywords:
Key words osteoarthritis;  Duhuo Jisheng Tang;  cartilage degeneration;  G protein coupled signaling pathway;  animal experimentation
摘要:
目的:探讨独活寄生汤对骨关节炎软骨退变的影响及其作用机制。方法:将45只8周龄雄性SD大鼠随机分为空白组、模型组、独活寄生汤组,每组15只。模型组、独活寄生汤组采用改良Hulth法建立膝骨关节炎大鼠模型,空白组不做任何处理。独活寄生汤组给予9.3 g·kg-1的独活寄生汤水煎浓缩液进行灌胃,模型组和空白组给予等剂量生理盐水灌胃; 每天灌胃1次,连续灌胃12周。末次灌胃后分别取各组大鼠双侧股骨髁,采用HE染色观察关节软骨组织形态,并采用Mankin's关节软骨组织学评分法评价软骨退变程度; 采用Western blot法检测软骨中G蛋白偶联信号传导系统的关键调控因子的蛋白表达情况。分别从模型组和独活寄生汤组各取50 mg关节软骨组织,采用基因芯片检测软骨基质降解基因表达情况。结果:①软骨组织形态。空白组关节软骨结构层次清晰,潮线完整,软骨表面较为平滑; 模型组关节软骨结构层次较为紊乱,未见潮线,表层软骨膜破损,膜样结构消失并呈丝绒样; 独活寄生汤组关节软骨结构层次较为清晰,软骨破坏程度比模型组轻。②软骨退变程度。3组大鼠关节软骨的Mankin's组织学评分比较,差异有统计学意义[(3.46±2.04)分,(12.58±2.55)分,(7.75±1.91)分,F=13.114,P=0.006]; 空白组和独活寄生汤组低于模型组(t=-5.114,P=0.002; t=2.709,P=0.035); 空白组与独活寄生汤组比较,差异无统计学意义(t=-2.406,P=0.053)。③药物干预后G蛋白偶联信号传导系统关键调控因子的蛋白表达。3组大鼠G蛋白偶联信号传导系统关键调控因子Gαs、Gαq、Gαo、Gαi蛋白表达量比较,组间差异均有统计学意义[(1.59±0.09)kDa,(1.01±0.04)kDa,(1.45±0.14)kDa,F=29.760,P=0.001;(1.03±0.06)kDa,(0.53±0.04)kDa,(0.75±0.09)kDa,F=14.969,P=0.027;(0.36±0.02)kDa,(0.11±0.01)kDa,(0.17±0.02)kDa,F=204.105,P=0.000;(0.20±0.02)kDa,(0.56±0.05)kDa,(0.33±0.07)kDa,F=28.357,P=0.001]; 空白组Gαs、Gαq、Gαo表达量均高于模型组(t=0.407,P=0.000; t=0.546,P=0.012; t=1.933,P=0.000),Gαi表达量低于模型组(t=-0.750,P=0.000); 模型组Gαs、Gαq、Gαo表达量均低于独活寄生汤组(t=-5.584,P=0.001; t=-2.431,P=0.093; t=-4.584,P=0.004),Gαi表达量高于独活寄生汤组(t=4.377,P=0.005); 独活寄生汤组Gαs、Gαq表达量与空白组比较,组间差异均无统计学意义(t=-1.816,P=0.119; t=-3.029,P=0.056); 独活寄生汤组Gαo表达量低于空白组(t=-14.749,P=0.000),Gαi表达量高于空白组(t=3.119,P=0.021)。④药物干预后关节软骨基质降解基因的表达。药物干预后,表达上调2倍以上的软骨基质降解基因为基质金属蛋白酶(matrix metalloproteinase,MMP)8、硒蛋白P(selenoprotein P,SELP),表达下调2倍以上的软骨基质降解基因为蛋白聚糖酶(a disintegrin and metalloproteinase with thrombospondin motifs,ADAMTS)1、ADAMTS2、ADAMTS8、钙黏蛋白3(cadherin 3,CDH3)、胶原(collagen,COL)1A1、COL5A1、结缔组织生长因子(connective tissue growth factor,CTGF)、整合素(integrin,ITG)b1、ITGb4、MMP12、MMP14。模型组MMP8、SELP基因表达量均低于独活寄生汤组(1.00±0.00,2.81±0.60,t=-5.225,P=0.035; 1.00±0.00,2.31±0.81,t=-2.808,P=0.107),ADAMTS1、ADAMTS2、ADAMTS8、CDH3、COL1A1、COL5A1、CTGF、ITGb1、ITGb4、MMP12、MMP14基因表达量均高于独活寄生汤组(1.00±0.00,0.21±0.05,t=27.366,P=0.001; 1.00±0.00,0.31±0.16,t=7.458,P=0.018; 1.00±0.00,0.11±0.04,t=38.538,P=0.001; 1.00±0.00,0.30±0.23,t=5.271,P=0.034; 1.00±0.00,0.12±0.09,t=17.380,P=0.003; 1.00±0.00,0.09±0.16,t=10.168,P=0.010; 1.00±0.00, 0.21±0.30,t=4.605,P=0.044; 1.00±0.00,0.37±0.20,t=5.456,P=0.032; 1.00±0.00,0.13±0.22,t=6.960,P=0.020; 1.00±0.00,0.05±0.08,t=19.388,P=0.003; 1.00±0.00,0.05±0.10,t=15.671,P=0.004)。结论:独活寄生汤可以明显延缓骨关节炎软骨的退变,其作用机制可能是通过激活G蛋白偶联信号传导通路而抑制软骨基质降解,从而使受损的软骨组织修复,但其具体作用靶点有待进一步深入研究。
Abstract:
ABSTRACT Objective:To explore the effects of Duhuo Jisheng Tang(独活寄生汤,DHJST)on cartilage degeneration in the process of osteoarthritis(OA)and the mechanism of action.Methods:Forty-five 8-week-old male SD rats were randomly divided into blank group,model group and DHJST group,15 cases in each group.The knee OA models were built by modified Hulth method in rats of model group and DHJST group,while the rats in blank group were not given any surgical intervention.The rats in DHJST group were intragastric administrated with DHJST concentrated solution in dosages of 9.3 g/kg,while the rats in model group and blank group were intragastric administrated with isodose normal saline,once a day for consecutive 12 weeks.The bilateral femoral condyles of rats in each group were fetched out respectively after the last intragastric administration.The articular cartilage tissue forms were observed after HE staining and the degrees of cartilage degeneration were evaluated by using Mankin's articular cartilage histological scores.The protein expression of key regulating factor of G protein coupled signal transduction systems in the cartilage were detected by using Western blot method.The articularological scores.The protein expression of key regulating factor of G protein coupled signal transduction systems in the cartilage were detected by using Western blot method.The articular cartilage(50 mg)were taken from the rats in model group and DHJST group respectively,and the cartilage matrix degradation gene expression were detected by using gene chips.Results:Clear articular cartilage structure,complete tidal line and smooth cartilage surface were found in blank group.Relatively disorderly articular cartilage structure and damaged surface perichondrium were found and tidal line and membrane structure disappeared in model group.Relatively clear articular cartilage structure and slighter cartilage destruction were found in DHJST group.There was statistical difference in Mankin's histological scores of articular cartilage between the 3 groups(3.46+/-2.04,12.58+/-2.55,7.75+/-1.91 points,F=13.114,P=0.006).The Mankin's histological scores were lower in blank group and DHJST group compared to model group(t=-5.114,P=0.002; t=2.709,P=0.035).There was no statistical difference in Mankin's histological scores between blank group and DHJST group(t=-2.406,P=0.053).There was statistical difference in the protein expression of key regulating factor Gαs,Gαq,Gαo and Gαi of G protein coupled signal transduction systems between the 3 groups(1.59+/-0.09,1.01+/-0.04,1.45+/-0.14 kDa,F=29.760,P=0.001; 1.03+/-0.06,0.53+/-0.04,0.75+/-0.09 kDa,F=14.969,P=0.027; 0.36+/-0.02,0.11+/-0.01,0.17+/-0.02 kDa,F=204.105,P=0.000; 0.20+/-0.02,0.56+/-0.05,0.33+/-0.07 kDa,F=28.357,P=0.001).The expressions of Gαs,Gαq and Gαo were higher and the expressions of Gαi were lower in blank group compared to model group(t=0.407,P=0.000; t=0.546,P=0.012; t=1.933,P=0.000; t=-0.750,P=0.000).The expressions of Gαs,Gαq and Gαo were lower and the expressions of Gαi were higher in model group compared to DHJST group(t=-5.584,P=0.001; t=-2.431,P=0.093; t=-4.584,P=0.004; t=4.377,P=0.005).There was no statistical difference in the expressions of Gαs and Gαq between blank group and DHJST group(t=-1.816,P=0.119; t=-3.029,P=0.056).The expressions of Gαo were lower and the expressions of Gαi were higher in DHJST group compared to blank group(t=-14.749,P=0.000; t=3.119,P=0.021).After drug intervention,the expression of some cartilage matrix degradation genes,including matrix metalloproteinase(MMP)8 and selenoprotein P(SELP),were up-regulated more than 2 times; while the expression of some cartilage matrix degradation genes,including a disintegrin and metalloproteinase with thrombospondin motifs(ADAMTS)1,ADAMTS2,ADAMTS8,cadherin 3(CDH3),collagen(COL)1A1,COL5A1,connective tissue growth factor(CTGF),integrin(ITG)b1,ITGb4,MMP12 and MMP14 were down-regulated more than 2 times.The gene expression levels of MMP8 and SELP were lower in model group compared to DHJST group(1.00+/-0.00 vs 2.81+/-0.60,t=-5.225,P=0.035; 1.00+/-0.00 vs 2.31+/-0.81,t=-2.808,P=0.107),while the gene expression levels of ADAMTS1,ADAMTS2,ADAMTS8,CDH3,COL1A1,COL5A1,CTGF,ITGb1,ITGb4,MMP12 and MMP14 were higher in model group compared to DHJST group(1.00+/-0.00 vs 0.21+/-0.05,t=27.366,P=0.001; 1.00+/-0.00 vs 0.31+/-0.16,t=7.458,P=0.018; 1.00+/-0.00 vs 0.11+/-0.04,t=38.538,P=0.001; 1.00+/-0.00 vs 0.30+/-0.23,t=5.271,P=0.034; 1.00+/-0.00 vs 0.12+/-0.09,t=17.380,P=0.003; 1.00+/-0.00 vs 0.09+/-0.16,t=10.168,P=0.010; 1.00+/-0.00 vs 0.21+/-0.30,t=4.605,P=0.044; 1.00+/-0.00 vs 0.37+/-0.20,t=5.456,P=0.032; 1.00+/-0.00 vs 0.13+/-0.22,t=6.960,P=0.020; 1.00+/-0.00 vs 0.05+/-0.08,t=19.388,P=0.003; 1.00+/-0.00 vs 0.05+/-0.10,t=15.671,P=0.004).Conclusion:DHJST can obviously delay cartilage degeneration in the process of OA.The mechanisms of action may be that it can inhibit cartilage matrix degradation through activating G protein coupled signaling pathway,so it can repair the damaged cartilage tissues.However,its specific action targets need to be further studied.

参考文献/References:

[1] CORR EM,CUNNINGHAM CC,HELBERT L,et al.Osteoarthritis-associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells[J].Arthritis Res Ther,2017,19(1):23.
[2] MOUSSA M,LAJEUNESSE D,HILAL G,et al.Platelet rich plasma(PRP)induces chondroprotection via increasing autophagy,anti-inflammatory markers,and decreasing apoptosis in human osteoarthritic cartilage[J].Exp Cell Res,2017,352(1):146-156.
[3] 李西海,张翼,叶蕻芝,等.独活寄生汤治疗风寒湿痹型膝骨关节炎的机制[J].中医正骨,2012,24(1):68-71.
[4] 林木南,刘献祥,王水良,等.治疗型关节炎护膝对实验性骨关节炎软骨细胞凋亡基因Bcl-2及p53的影响[J].中国骨伤,2009,22(9):688-691.
[5] 郑文伟,马玉环,陈后煌,等.跳骨片抑制大鼠膝骨关节炎Wnt/β-catenin信号转导通路介导炎症反应的机制研究[J].国际骨科学杂志,2017,38(1):60-64.
[6] 林木南,刘献祥,李西海,等.治疗型关节炎护膝对膝骨关节炎兔关节液中转化生长因子β及胰岛素样生长因子的影响[J].中医正骨,2012,24(1):11-14.
[7] 黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072. 中医正骨2017年7月第29卷第7期 J Trad Chin Orthop Trauma,2017,Vol.29,No.7(总491) (总492)中医正骨2017年7月第29卷第7期 J Trad Chin Orthop Trauma,2017,Vol.29,No.7
[8] MANKIN HJ,JOHNSON ME,LIPPIELLO L.Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips.III. Distribution and metabolism of amino sugar-containing macromolecules[J].J Bone Joint Surg Am,1981,63(1):131-139.
[9] 李西海,陈文列,刘献祥.补肾柔肝法防治骨性关节炎作用机制探讨[J].福建中医药大学学报,2011,21(2):66-69.
[10] 周肃陵,刘肖瑜,王正.独活寄生汤在骨伤科的临床应用[J].中医正骨,2006,18(12):67-69.
[11] 卢跃卿,任小巧,邢海燕.中医肝肾同源与神经内分泌免疫网络关系[J].中华实用中西医杂志,2000,13(4):765.
[12] 王耀光.“肝肾同源”论初探[J].中医杂志,2008,49(1):5-7.
[13] STEFFENS B,SAUTER M.G proteins as regulators in ethylene-mediated hypoxia signaling[J].Plant Signal Behav,2010,5(4):375-378.
[14] TESMER JJ.The quest to understand heterotrimeric G protein signaling[J].Nat Struct Mol Biol,2010,17(6):650-652.
[15] BASCOUL-COLOMBO C,GARAIOVA I,PLUMMER SF,et al.Glucosamine hydrochloride but not chondroitin sulfate prevents cartilage degradation and inflammation induced by interleukin-1α in bovine cartilage explants[J].Cartilage,2016,7(1):70-81.
[16] 邵翔,陈后煌,陈达,等.透骨消痛胶囊抑制脂多糖诱导软骨细胞炎症反应的机制研究[J].国际骨科学杂志,2016,37(6):406-410.
[17] WANG CC,GUO L,TIAN FD,et al.Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model[J].Brazilian Journal of Medical and Biological Research,2017,50(4):e5714.
[18] ZHANG Y,LIN J,WEI F.The function and roles of ADAMTS-7 in inflammatory diseases[J].Mediators Inflamm,2015,(9):1-11.
[19] MONFOULET LE,PHILIPPE C,MERCIER S,et al.Deficiency of G-protein coupled receptor 40,a lipid-activated receptor,heightens in vitro- and in vivo-induced murine osteoarthritis[J].Exp Biol Med(Maywood),2015,240(7):854-866.
[20] VARANI K,VINCENZI F,TOSI A,et al.Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes[J].Br J Pharmacol,2010,160(1):101-115.
[21] BERG V,SVEINBJÖRNSSON B,BENDIKSEN S,et al.Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin 21-157[J].Arthritis Res Ther,2010,12(6):R228.
[22] 刘俊才,陈友霞,李忠,等.整合素α5β1在膝骨关节炎不同退变程度关节软骨中的差异性表达[J].中国组织工程研究,2017,21(8):1155-1160.

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[12]何晓娟,林平冬,马玉环,等.独活寄生汤含药血清抑制白细胞介素1β诱导的软骨细胞炎症反应的作用机制研究[J].中医正骨,2017,29(08):1.
　HE Xiaojuan,LIN Pingdong,MA Yuhuan,et al.Study on mechanism of action of Duhuo Jisheng Tang(独活寄生汤)medicated serum in inhibiting inflammatory reaction induced by interleukin-1 beta in chondrocytes[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2017,29(07):1.
[13]陈俊,吴广文,许惠凤,等.独活寄生汤含药血清对大鼠退变软骨细胞蛋白激酶 R样内质网激酶/免疫球蛋白结合蛋白信号通路的影响[J].中医正骨,2018,30(08):1.
　CHEN Jun,WU Guangwen,XU Huifeng,et al.Effect of Duhuo Jisheng Tang(独活寄生汤)medicated serum on protein kinase R-like endoplasmic reticulum kinase/immunoglobulin-binding protein signaling pathway in degenerated chondrocytes of rats[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2018,30(07):1.
[14]朱勇,李艺彬,王世捷,等.关节镜清理术配合口服独活寄生汤 治疗膝骨关节炎肝肾亏虚证[J].中医正骨,2018,30(09):73.
[15]周江涛,赵依娜,王庆来.独活寄生汤口服联合玻璃酸钠关节腔注射治疗早中期膝骨关节炎[J].中医正骨,2019,31(02):18.
　ZHOU Jiangtao,ZHAO Yina,WANG Qinglai.Oral application of Duhuo Jisheng Tang(独活寄生汤)combined with intra-articular injection of sodium hyaluronate for treatment of early-middle knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2019,31(07):18.
[16]郑梓灌,林涛,吴丽芳.独活寄生汤口服联合二乌红花饮离子导入治疗膝骨关节炎肾虚髓亏证[J].中医正骨,2019,31(05):38.
[17]许丽梅,李慧,许云腾,等.基于NF-κB信号通路探讨独活寄生汤抑制脂多糖诱导的软骨细胞炎症反应的作用机制[J].中医正骨,2019,31(07):9.
　XU Limei,LI Hui,XU Yunteng,et al.An experimental study of mechanism of action of Duhuo Jisheng Tang(独活寄生汤)in inhibiting inflammatory reaction induced by lipopolysaccharide in chondrocytes based on NF-κB signaling pathway[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2019,31(07):9.
[18]黄岩石.独活寄生汤口服联合富血小板血浆关节腔内注射治疗膝骨关节炎的临床研究[J].中医正骨,2021,33(02):1.
　HUANG Yanshi.A clinical study of oral application of Duhuo Jisheng Tang(独活寄生汤)combined with intra-articular injection of platelet-rich plasma for treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2021,33(07):1.
[19]韩玫,李贞,曹建西.温针灸联合口服独活寄生汤治疗膝骨关节炎寒湿痹阻证[J].中医正骨,2021,33(06):67.
[20]陈俊,郑若曦,叶锦霞,等.独活寄生汤治疗大鼠膝骨关节炎的作用机制研究[J].中医正骨,2021,33(11):6.
　CHEN Jun,ZHENG Ruoxi,YE Jinxia,et al.Study on mechanism of action of Duhuo Jisheng Tang(独活寄生汤)in treatment of knee osteoarthritis in rats[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2021,33(07):6.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金项目(81373818) 通讯作者:李西海 E-mail:lixihai79dahai@163.com mechanism of action
更新日期/Last Update: 2017-12-29