淫羊藿苷治疗骨性关节炎的研究进展
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摘要
骨性关节炎是一种好发于负重较大的膝关节、髋关节及脊柱等部位的慢性关节疾病,其病因复杂,至今尚未阐明。随着我国人口老龄化的加剧,骨关节炎的发病率不断增高,2015年统计数据发现我国大陆地区骨性关节炎的发病率约为13%。目前临床上针对骨性关节炎有保守及手术等疗法,如膝关节骨性关节炎可保守治疗也可行单髁置换、胫骨高位截骨及双间室置换等手术疗法,手术治疗创伤大,费用高,远期效果并非一劳永逸。而现有的保守疗法远期效果并不显著,所以寻找新的有效的治疗药物显得更为迫切。近年来研究发现淫羊藿苷在治疗骨关节炎方面有着显著的作用,它可促进骨髓间充质干细胞成软骨分化及促进软骨细胞增殖,有效修复骨性关节炎所致的软骨病损;可抑制软骨细胞外基质的降解,延缓骨关节炎所致的软骨组织破坏;可促进成骨细胞增殖,在骨性关节炎早期促进成骨及解除矿化障碍,阻止软骨下骨的进一步病变;可抑制破骨细胞的破骨作用,达到保护软骨下骨的目的;还可抑制炎症因子所致的滑膜炎症反应,缓解关节炎所致疼痛等症状。总之,淫羊藿苷可有效治疗骨性关节炎,尤以早期为著。目前的研究仅局限于组织细胞及动物实验,为明确淫羊藿苷治疗骨性关节炎的有效性及安全性,尚需更多的临床型研究予以证实,这也是今后的研究方向。
Osteoarthritis is a chronic joint disease that occurs in areas of greater weight-bearing,such as knee,hip and spine. The etiology is complex and has not been fully elucidated yet. With the aggravation of population aging in our country,the incidence of osteoarthritis continues to increase. Statistics show that the incidence of osteoarthritis in mainland China is around 13%. The current clinical treatment of osteoarthritis including conservative and surgical therapy. For example, knee osteoarthritis could have conservative treatment or unicompartmental knee arthroplasty,high tibial osteotomy and double room replacement surgery,etc.Surgical treatment can treat knee osteoarthritis,but involves trauma and high cost,and the effect of the existing conservative treatment is not significant,so finding effective treatment of osteoarthritis becomes even more urgent. In recent years,studies have shown that Icariin has a positive and significant role in the treatment of osteoarthritis. It could effectively promote bone marrow mesenchymal stem cells differentiate into cartilage,promote chondrocyte proliferation,and repair cartilage lesions caused by osteoarthritis. It can inhibit the degradation of cartilage extracellular matrix,and delay the destruction of cartilage tissue caused by osteoarthritis. It can also promote osteoblast proliferation,promote osteogenesis and normalize demineralization disorders at early stage osteoarthritis to prevent further subchondral bone lesions. It can also inhibit osteoclasts activity,and thus protect the subchondral bone. In addition,it can inhibit inflammatory factor-induced synovitis,and relieve pain and other symptoms caused by arthritis. In short,Icariin can treat osteoarthritis effectively,especially in the early stage. Currently studies are limited to tissue and animal experiments,in order to clarify the effectiveness of Icariin in the treatment of osteoarthritis,more clinical studies are needed,which is the direction of future research.
Osteoarthritis is a chronic joint disease that occurs in areas of greater weight-bearing,such as knee,hip and spine. The etiology is complex and has not been fully elucidated yet. With the aggravation of population aging in our country,the incidence of osteoarthritis continues to increase. Statistics show that the incidence of osteoarthritis in mainland China is around 13%. The current clinical treatment of osteoarthritis including conservative and surgical therapy. For example, knee osteoarthritis could have conservative treatment or unicompartmental knee arthroplasty,high tibial osteotomy and double room replacement surgery,etc.Surgical treatment can treat knee osteoarthritis,but involves trauma and high cost,and the effect of the existing conservative treatment is not significant,so finding effective treatment of osteoarthritis becomes even more urgent. In recent years,studies have shown that Icariin has a positive and significant role in the treatment of osteoarthritis. It could effectively promote bone marrow mesenchymal stem cells differentiate into cartilage,promote chondrocyte proliferation,and repair cartilage lesions caused by osteoarthritis. It can inhibit the degradation of cartilage extracellular matrix,and delay the destruction of cartilage tissue caused by osteoarthritis. It can also promote osteoblast proliferation,promote osteogenesis and normalize demineralization disorders at early stage osteoarthritis to prevent further subchondral bone lesions. It can also inhibit osteoclasts activity,and thus protect the subchondral bone. In addition,it can inhibit inflammatory factor-induced synovitis,and relieve pain and other symptoms caused by arthritis. In short,Icariin can treat osteoarthritis effectively,especially in the early stage. Currently studies are limited to tissue and animal experiments,in order to clarify the effectiveness of Icariin in the treatment of osteoarthritis,more clinical studies are needed,which is the direction of future research.
引文
[1]吴迎春,吕刚,依力潘·凯赛尔,等.淫羊藿总黄酮联合硫酸氨基葡萄糖对膝骨关节炎疗效临床研究[J].中国骨质疏松杂志,2017,23(9):1195-1198.Wu YC,Lu G,Yilipan K,et al.The clinical research of the efficacy of epimedium total flavone combined with glucosamine sulfate on knee osteoarthritis[J].Chin J Osteoporos,2017,23(9):1195-1198.(in Chinese)
[2]程千,魏雅君,蒋俊,等.基于再生机制的淫羊藿黄酮在骨细胞微环境的药代动力学研究思路与方法[J].中国骨质疏松杂志,2017,23(6):824-830.Cheng Q,Wei YJ,Jiang J,et al.Research ideas and methods for the pharmacokinetics of epimedium flavonoids with different glycosylation number,type or location in bone cell microenvironment[J].Chin J Osteoporos,2017,23(6):824-830.(in Chinese)
[3]黄明炜,廖勇敢.淫羊藿总黄酮调节骨代谢作用及药理机制的研究新进展[J].中国骨质疏松杂志,2014,20(4):452-456.Huang MW,Liao YG.Research progress in the regulating effect of epimedium flavonoids on bone metabolism and its pharmacological mechanism[J].Chin J Osteoporos,2014,20(4):452-456.(in Chinese)
[4]黄荷,曾意荣,简林养,等.淫羊藿甙诱导人骨髓间充质干细胞向软骨细胞分化实验研究[J].新中医,2016,48(1):210-212.Huang H,Zeng YR,Jian LY,et al.Experimental Study on Icariin Inducing Human Bone Marrow Mesenchymal Stem Cells to Differentiate into Chondrocyte[J].New Chinese Medicine,2016,48(1):210-212.(in Chinese)
[5]汪建样,殷嫦嫦,武翠翠,等.淫羊藿素通过Wnt/β-catenin信号通路促进BMSCs成软骨分化[J].中国中药杂志,2016,41(4):694-699.Wang JY,Yin CC,Wu CC,et al.Icaritin promotes chondrogenic differentiation of BMSCs by Wnt/β-catenin signaling pathway[J].Chinese Journal of Traditional Chinese Medicine,2016,41(4):694-699.(in Chinese)
[6]何李乐,王万春.淫羊藿素对大鼠软骨细胞作用的实验研究[J].中南大学学报(医学版),2015,40(5):517-521.He LL,Wang WC.Effect of icariin on chondrocytes in rats[J].Chinese Journal of Central South University(Medical Science),2015,40(5):517-521.(in Chinese)
[7]冯坤,谢文,陈宝龙,等.5种淫羊藿对软骨组织生长和软骨细胞增殖影响的对比研究[C].中医药优秀论文选,2009:2065-2067.Feng K,Xie W,Chen BL,et al.Promoting Effect of Epimedium on Cartilage Growth in Vitro[C].Chinese medicine outstanding essay selection,2009:2065-2067.(in Chinese)
[8]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(6):25-27.Zhang X,Xiao YM,Wang R,et al.Effect of Icariin on Chondrocyte Growth and Extracellular Matrix Secretion in Collagen Scaffolds[J].Pharmacology and Clinical Medicine,2010(6):25-27.(in Chinese)
[9]张蕾,程瑜,金王东,等.药用植物淫羊藿与富血小板血浆协同对软骨细胞的增殖作用[J].浙江农业学报,2014,26(3):680-684.Zhang L,Cheng Y,Jin WD,et al.Study of Medicinal Plant Epimedium Brevicornum Maxim and Platelet Effects on Chondrocyte Proliferation[J].Acta Agriculturae Zhejiang gensis,2014,26(3):680-684.(in Chinese)
[10]黄少君,孙升云,徐梅,等.淫羊藿对早期兔膝骨性关节炎软骨的影响[J].暨南大学学报(自然科学与医学版),2014,35(3):273-278.Huang SJ,Sun SY,Xu M,et al.Effect of epimedium in cartilage of osteoarthritic knee of rabbits in the early stage[J].Journal of Jinan University(Natural Science&Medicine Edition),2014,35(3):273-278.(in Chinese)
[11]葛茂林,李志强,舒清明,等.淫羊藿苷对早期兔膝关节骨性关节炎的影响[J].武警后勤学院学报(医学版),2011,20(12):954-957.Ge ML,Li ZQ,Shu QM,et al.Effect of Icariin on the osteoarthritic knee of rabbits in the early stage[J].Acta Academiae Medicinae CPAF,2011,20(12):954-957.(in Chinese)
[12]柯勇,张功礼,禹志宏,等.淫羊藿苷对体外培养的成骨细胞骨形态发生蛋白-2表达的影响[J].湖北医药学院学报,2008,27(3):202-204.Ke Y,Zhang GL,Yu ZH,et al.Effects of icariin on the expression of osteoblast BMP-2 in vitro[J].Journal of Yunyang Medical College,2008,27(3):202-204.(in Chinese)
[13]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].南京医科大学博士学位论文,2016.Gao KD.Protective effect of icariin on subchondral bone in osteoarthritic mice and its mechanism[D].Nanjing Medical University Doctoral Dissertation,2016.(in Chinese)
[14]张秀珍,杨黎娟.淫羊藿甙对大鼠成骨细胞护骨素、RANKL表达的影响[J].中华内分泌代谢杂志,2006,22(3):222-225.Zhang XZ,Yang LJ.Effects of icariin on the expression of osteoprotegerin and RANK-L of rat osteoblasts[J].Chinese Journal of Endocrinology and Metabolism,2006,22(3):222-225.(in Chinese)
[15]刘亦恒,臧洪敏,张海英,等.淫羊藿总黄酮对成骨细胞中OPG和RANK-LmRNA基因表达影响的实验研究[J].中药材,2005,28(12):1076-1078.Liu YH,Zang HM,Zhang HY,et al.Effects of Epimedium Flavonoids on OPG and RANK-L mRNA Gene Expression in Osteoblasts[J].Chinese Materia Medica,2005,28(12):1076-1078.(in Chinese)
[16]刘益杰,冯伟,何东仪,等.淫羊藿苷对Ⅱ型胶原诱导型关节炎大鼠骨破坏及血清RANK-L/OPG的干预作用[J].中国中西医结合杂志,2013,33(9):1221-1225.Liu YJ,Fen W,He DY,et al.Effect of icariin on bone destruction and serum RANK-L/OPG in typeⅡcollagen-induced arthritis in rats[J].Chinese Integrative Medicine,2013,33(9):1221-1225.(in Chinese)
[17]潘连红.淫羊藿苷对骨关节炎滑膜细胞中MMP14表达和细胞增殖调控的研究[D].重庆大学硕士学位论文,2016.Pan LH.Icariin on osteoarthritis synovial cells MMP14 expression and cell proliferation regulation[D].Chongqing University Master's degree thesis,2016.(in Chinese)
[2]程千,魏雅君,蒋俊,等.基于再生机制的淫羊藿黄酮在骨细胞微环境的药代动力学研究思路与方法[J].中国骨质疏松杂志,2017,23(6):824-830.Cheng Q,Wei YJ,Jiang J,et al.Research ideas and methods for the pharmacokinetics of epimedium flavonoids with different glycosylation number,type or location in bone cell microenvironment[J].Chin J Osteoporos,2017,23(6):824-830.(in Chinese)
[3]黄明炜,廖勇敢.淫羊藿总黄酮调节骨代谢作用及药理机制的研究新进展[J].中国骨质疏松杂志,2014,20(4):452-456.Huang MW,Liao YG.Research progress in the regulating effect of epimedium flavonoids on bone metabolism and its pharmacological mechanism[J].Chin J Osteoporos,2014,20(4):452-456.(in Chinese)
[4]黄荷,曾意荣,简林养,等.淫羊藿甙诱导人骨髓间充质干细胞向软骨细胞分化实验研究[J].新中医,2016,48(1):210-212.Huang H,Zeng YR,Jian LY,et al.Experimental Study on Icariin Inducing Human Bone Marrow Mesenchymal Stem Cells to Differentiate into Chondrocyte[J].New Chinese Medicine,2016,48(1):210-212.(in Chinese)
[5]汪建样,殷嫦嫦,武翠翠,等.淫羊藿素通过Wnt/β-catenin信号通路促进BMSCs成软骨分化[J].中国中药杂志,2016,41(4):694-699.Wang JY,Yin CC,Wu CC,et al.Icaritin promotes chondrogenic differentiation of BMSCs by Wnt/β-catenin signaling pathway[J].Chinese Journal of Traditional Chinese Medicine,2016,41(4):694-699.(in Chinese)
[6]何李乐,王万春.淫羊藿素对大鼠软骨细胞作用的实验研究[J].中南大学学报(医学版),2015,40(5):517-521.He LL,Wang WC.Effect of icariin on chondrocytes in rats[J].Chinese Journal of Central South University(Medical Science),2015,40(5):517-521.(in Chinese)
[7]冯坤,谢文,陈宝龙,等.5种淫羊藿对软骨组织生长和软骨细胞增殖影响的对比研究[C].中医药优秀论文选,2009:2065-2067.Feng K,Xie W,Chen BL,et al.Promoting Effect of Epimedium on Cartilage Growth in Vitro[C].Chinese medicine outstanding essay selection,2009:2065-2067.(in Chinese)
[8]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(6):25-27.Zhang X,Xiao YM,Wang R,et al.Effect of Icariin on Chondrocyte Growth and Extracellular Matrix Secretion in Collagen Scaffolds[J].Pharmacology and Clinical Medicine,2010(6):25-27.(in Chinese)
[9]张蕾,程瑜,金王东,等.药用植物淫羊藿与富血小板血浆协同对软骨细胞的增殖作用[J].浙江农业学报,2014,26(3):680-684.Zhang L,Cheng Y,Jin WD,et al.Study of Medicinal Plant Epimedium Brevicornum Maxim and Platelet Effects on Chondrocyte Proliferation[J].Acta Agriculturae Zhejiang gensis,2014,26(3):680-684.(in Chinese)
[10]黄少君,孙升云,徐梅,等.淫羊藿对早期兔膝骨性关节炎软骨的影响[J].暨南大学学报(自然科学与医学版),2014,35(3):273-278.Huang SJ,Sun SY,Xu M,et al.Effect of epimedium in cartilage of osteoarthritic knee of rabbits in the early stage[J].Journal of Jinan University(Natural Science&Medicine Edition),2014,35(3):273-278.(in Chinese)
[11]葛茂林,李志强,舒清明,等.淫羊藿苷对早期兔膝关节骨性关节炎的影响[J].武警后勤学院学报(医学版),2011,20(12):954-957.Ge ML,Li ZQ,Shu QM,et al.Effect of Icariin on the osteoarthritic knee of rabbits in the early stage[J].Acta Academiae Medicinae CPAF,2011,20(12):954-957.(in Chinese)
[12]柯勇,张功礼,禹志宏,等.淫羊藿苷对体外培养的成骨细胞骨形态发生蛋白-2表达的影响[J].湖北医药学院学报,2008,27(3):202-204.Ke Y,Zhang GL,Yu ZH,et al.Effects of icariin on the expression of osteoblast BMP-2 in vitro[J].Journal of Yunyang Medical College,2008,27(3):202-204.(in Chinese)
[13]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].南京医科大学博士学位论文,2016.Gao KD.Protective effect of icariin on subchondral bone in osteoarthritic mice and its mechanism[D].Nanjing Medical University Doctoral Dissertation,2016.(in Chinese)
[14]张秀珍,杨黎娟.淫羊藿甙对大鼠成骨细胞护骨素、RANKL表达的影响[J].中华内分泌代谢杂志,2006,22(3):222-225.Zhang XZ,Yang LJ.Effects of icariin on the expression of osteoprotegerin and RANK-L of rat osteoblasts[J].Chinese Journal of Endocrinology and Metabolism,2006,22(3):222-225.(in Chinese)
[15]刘亦恒,臧洪敏,张海英,等.淫羊藿总黄酮对成骨细胞中OPG和RANK-LmRNA基因表达影响的实验研究[J].中药材,2005,28(12):1076-1078.Liu YH,Zang HM,Zhang HY,et al.Effects of Epimedium Flavonoids on OPG and RANK-L mRNA Gene Expression in Osteoblasts[J].Chinese Materia Medica,2005,28(12):1076-1078.(in Chinese)
[16]刘益杰,冯伟,何东仪,等.淫羊藿苷对Ⅱ型胶原诱导型关节炎大鼠骨破坏及血清RANK-L/OPG的干预作用[J].中国中西医结合杂志,2013,33(9):1221-1225.Liu YJ,Fen W,He DY,et al.Effect of icariin on bone destruction and serum RANK-L/OPG in typeⅡcollagen-induced arthritis in rats[J].Chinese Integrative Medicine,2013,33(9):1221-1225.(in Chinese)
[17]潘连红.淫羊藿苷对骨关节炎滑膜细胞中MMP14表达和细胞增殖调控的研究[D].重庆大学硕士学位论文,2016.Pan LH.Icariin on osteoarthritis synovial cells MMP14 expression and cell proliferation regulation[D].Chongqing University Master's degree thesis,2016.(in Chinese)