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Food Science and Human Wellness 2024年

作者： Huihui Xu Kai'ao Zou Haipeng Huang Qinghe Zeng Xu Wang Ping'er Wang Wenhua Yuan Luwei Xiao Jiali Chen peijian tong Hongting Jin he First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) The First College of Clinical Medicine， Zhejiang Chinese Medical University Institute of Orthopaedics and Traumatology of Zhejiang Province

The study aimed to explore the efficacy and potential mechanisms of a naturally aromatic cyanogenic compound-amygdalin (AMY) in treating glucocorticoid (GC)-associated necrosis of the femoral head (GANFH). We demonstrated that GC exacerbates the oxidative stress (OS) microenvironment via promoting nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression in human， rat， and mesenchymal stem cells (MSCs) samples， thus generating excessive ROS， leading to increased apoptosis and unbalanced osteolipogenic differentiation. Furthermore， computational docking results revealed that AMY could bind specifically to the predicted binding sites of NOX4. Additionally， AMY ameliorated the OS microenvironment of MSCs via decreasing NOX4 expression and inhibiting NOX4/ROS/p38MAPK signaling， thereby reversing the GC-induced apoptosis and imbalanced osteolipogenic differentiation， and ultimately alleviating GANFH. In summary， we demonstrated for the first time that AMY attenuated apoptosis and maintained osteolipogenic differentiation balance in MSCs via specifically targeting NOX4， inhibiting NOX4/ROS/p38MAPK signaling， thereby treating GANFH.

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中药黄酮类化合物在细胞程序性死亡介导的骨关节疾病中的作用机制研究进展

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中国现代应用药学 2024年第15期41卷 2126-2135页

作者：周旋缪毛毛李孟颖童培建寿旦张扬浙江中医药大学第四临床医学院杭州310053 浙江中医药大学药学院杭州310053 浙江中医药大学附属第一医院骨伤研究所基础研究部杭州310053

骨关节疾病的发生呈现年轻化趋势,且患病率逐渐升高,常见的疾病包括骨质疏松症、骨关节炎、类风湿关节炎等。细胞程序性死亡(programmed cell death,PCD)是生物体普遍存在的现象,与生物的生长发育、组织修复和疾病产生有关,主要包括细... 详细信息

骨关节疾病的发生呈现年轻化趋势,且患病率逐渐升高,常见的疾病包括骨质疏松症、骨关节炎、类风湿关节炎等。细胞程序性死亡(programmed cell death,PCD)是生物体普遍存在的现象,与生物的生长发育、组织修复和疾病产生有关,主要包括细胞凋亡、焦亡、自噬、铁死亡、坏死性凋亡、铜死亡和中性粒细胞外陷阱相关死亡(neutrophil extracellular traps-osis,NETosis)等。研究证实,PCD的过度激活或抑制在骨关节疾病中起至关重要的作用。近年来,采用中药活性黄酮类成分治疗骨关节疾病引起了人们广泛的关注,药理学研究表明,黄酮类化合物通过抑制或诱导骨功能细胞的PCD发挥作用。本文通过查阅近年来国内外中药黄酮类成分治疗骨关节疾病的文献,对中药黄酮类成分调控间充质干细胞、成骨细胞、软骨细胞、破骨细胞的凋亡、自噬、焦亡以及铁死亡机制进行系统性归纳和总结,为揭示中药治疗骨关节疾病的机制提供新思路和方法,为临床运用中医药防治骨关节疾病提供依据。

关键词：细胞程序性死亡骨关节疾病中药黄酮类化合物

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股骨头坏死患者疼痛灾难化的危险因素分析

中华骨与关节外科杂志 2024年第8期17卷 728-733页

作者：王春平郭珈宜孙超俊阳一丹刘又文童培建岳辰福建中医药大学中医骨伤及运动康复教育部重点实验室福州350122 河南省洛阳正骨医院(河南省骨科医院) 河南洛阳471002 浙江省中医院骨伤科杭州310006 河南省洛阳正骨医院循证医学中心河南洛阳471002

目的:分析股骨头坏死(ONFH)患者疼痛灾难化的危险因素。方法:选择2023年7—12月河南省洛阳正骨医院(河南省骨科医院)收治的210例ONFH患者为研究对象。收集患者一般资料,记录患者Harris髋关节评分,同时完成广泛性焦虑障碍量表(GAD-7)、... 详细信息

目的:分析股骨头坏死(ONFH)患者疼痛灾难化的危险因素。方法:选择2023年7—12月河南省洛阳正骨医院(河南省骨科医院)收治的210例ONFH患者为研究对象。收集患者一般资料,记录患者Harris髋关节评分,同时完成广泛性焦虑障碍量表(GAD-7)、患者健康问卷抑郁量表(PHQ-9)及疼痛灾难化量表(PCS)评估。明确ONFH患者疼痛灾难化的现患率。采用单因素及多因素线性回归分析对ONFH患者疼痛灾难化的危险因素进行分析。结果:ONFH患者疼痛灾难化的现患率为29.0%(61/210)。单因素及多因素线性回归分析结果表明,女性、独居、ARCOⅢ期及Ⅳ期、Harris髋关节疼痛评分、GAD-7评分、PHQ-9评分是ONFH患者疼痛灾难化评分的独立危险因素。结论:ONFH患者具有较为明显的疼痛灾难化倾向,女性、独居、ARCOⅢ期及Ⅳ期、髋关节疼痛、焦虑、抑郁是ONFH患者发生疼痛灾难化的危险因素。

关键词：股骨头坏死疼痛灾难化危险因素

肾髓同治方对膝骨关节炎模型小鼠的干预机制研究

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浙江中西医结合杂志 2024年第8期34卷 708-713页

作者：金敏伟王苏平童培建凌厚福浙江中医药大学附属第一医院(浙江省中医院)骨伤科杭州310061 杭州市临安区昌化中医骨伤医院骨科杭州311321

目的探讨肾髓同治方对小鼠膝骨关节炎(KOA)的疗效及其分子机制。方法24只雄性C57BL/6J小鼠,按照随机数字表法分为假手术组、模型组和肾髓同治方低(1.7 g/kg)、高(3.4 g/kg)剂量组,每组6只。模型组及肾髓同治方低、高剂量组通过内侧半月... 详细信息

目的探讨肾髓同治方对小鼠膝骨关节炎(KOA)的疗效及其分子机制。方法24只雄性C57BL/6J小鼠,按照随机数字表法分为假手术组、模型组和肾髓同治方低(1.7 g/kg)、高(3.4 g/kg)剂量组,每组6只。模型组及肾髓同治方低、高剂量组通过内侧半月板失稳术(DMM)构建KOA小鼠模型。治疗8周后,显微CT(Micro-CT)观察胫骨侧软骨下骨骨微结构,番红固绿染色观察组织病理变化,免疫组织化学染色检测Ⅱ型胶原(Col2a1)、基质金属蛋白酶13(MMP13)和磷酸化Smad2蛋白(pSmad2)的变化。结果与假手术组比较,模型组小鼠软骨下骨骨小梁厚度[(0.197±0.003)mm比(0.123±0.005)mm]和骨体积分数[(85.053±1.046)%比(47.032±2.803)%]显著增加,同时骨小梁分离度显著减小[(0.072±0.006)mm比(0.136±0.004)mm],差异有统计学意义(P<0.05);番红固绿病理染色发现关节软骨严重磨损,软骨厚度及面积减少,剩余软骨细胞多数呈肥大状态,软骨下骨硬化明显,国际骨关节炎研究学会评分(OARSI)得分显著提高[(5.167±0.753)分比(0.166±0.258)分,P<0.05];免疫组织化学染色发现胫骨侧关节软骨的Col2a1[(0.190±0.021)%比(0.465±0.024)%]及pSmad2[(0.156±0.013)%比(0.604±0.077)%]表达水平明显下降,MMP13[(0.438±0.034)%比(0.143±0.027)%]表达水平显著上升,差异具有统计学意义(P<0.05)。与模型组比较,肾髓同治方低剂量组和肾髓同治方高剂量组软骨下骨硬化情况得到明显改善,表现为骨小梁厚度[(0.168±0.002)mm、(0.160±0.001)mm比(0.197±0.003)mm]和骨体积分数[(61.220±1.127)%、(56.411±1.306)%比(85.053±1.046)%]显著降低及骨小梁分离度[(0.094±0.004)mm、(0.105±0.007)mm比(0.072±0.006)mm]显著增高;且关节软骨磨损明显减轻,软骨厚度得到保留,软骨下骨硬化得到显著改善,OARSI[(3.917±0.375)分、(3.000±0.316)分比(5.167±0.753)分]得分显著降低;Col2a1[(0.326±0.021)%、(0.375±0.016)%比(0.190±0.021)%]及pSmad2[(0.425±0.038)%、(0.517±0.030)%比(0.156±0.013)%]蛋白的表达水平显著提高,同时MMP13[(0.302±0.024)%、(0.263±0.015)%比(0.438±0.034)%]的表达水平显著下调,差异具有统计学意义(P<0.01)。结论肾髓同治方对小鼠KOA有防治作用,其主要机制可能与调控软骨细胞的TGF-β/Smad信号通路有关。

关键词：小鼠骨关节炎肾髓同治方软骨细胞 TGF-β/Smad信号通路

Effect of Huqian Wan on liver-Yin and kidney-Yin deficiency patterns in patients with knee osteoarthritis

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Journal of Traditional Chinese Medicine 2015年第4期35卷 417-421页

作者： Chen Qiqing Jin Hongting He Bin Wang Liang Xiao Luwei tong peijian the First Clinical Medical College Zhejiang Chinese Medical University Department of Orthopaedic Surgery Gansu Provincial Hospital of TCM Institute of Orthopaedics and Traumatology of Zhejiang Province Zhejiang Chinese Medical University Department of Orthopaedic Surgery the First Affiliated Hospital of Zhejiang Chinese Medical University

OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin deficiency knee osteoarthritis(KOA).METHODS: One hundred patients were randomly divided into a treatment(50 patients) and control group(50 patients). In the treatment group, patients orally took the Chinese medicine Huqian Wan. Control group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual analog scale(VAS), Western Ontario and Mc Master University Osteoarthritis Index(WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey(SF36) were used to evaluate the curative effect before treatment and after 8 and 16 weeks of ***: VAS and WOMAC scores significantly decreased and SF 36 scores significantly increased after treatment in both groups compared with before treatment(P 0.05).CONCLUSION: Huqian Wan could effectively improve the clinical symptoms and quality of life in patients with KOA. It could also have a better and longer lasting curative effect without obvious adverse events compared with Votalin.

关键词： Osteoarthritis Knee Liver kidney Yin deficiency Treatment outcome Huqian Wan

颈后路Delta大通道全内镜技术治疗脊髓型和神经根型颈椎病的疗效分析

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中华创伤骨科杂志 2023年第1期25卷 82-87页

作者：陆龙卫徐佳隆童培建嘉兴市秀洲区人民医院(嘉兴市秀洲区新塍医院)骨科嘉兴314015 浙江省中医院骨伤科杭州310006

目的探讨颈后路Delta大通道全内镜技术治疗脊髓型和神经根型颈椎病的疗效。方法回顾性分析2020年1月至2021年6月嘉兴市秀洲区人民医院(嘉兴市秀洲区新塍医院)骨科收治的15例脊髓型和神经根型颈椎病患者资料。其中男6例,女9例;年龄54~76... 详细信息

目的探讨颈后路Delta大通道全内镜技术治疗脊髓型和神经根型颈椎病的疗效。方法回顾性分析2020年1月至2021年6月嘉兴市秀洲区人民医院(嘉兴市秀洲区新塍医院)骨科收治的15例脊髓型和神经根型颈椎病患者资料。其中男6例,女9例;年龄54~76岁,平均66.2岁;责任节段:C_(3,4)3例,C_(4,5)4例,C_(5,6)7例,C_(6,7)1例。均采用颈后路Delta大通道全内镜技术治疗。通过比较患者术前、术后1、3个月、末次随访时颈椎功能障碍指数(NDI)、日本骨科协会(JOA)评分,以及末次随访时的改良Mac-Nab评分评价疗效,通过比较患者术前、术后1、3个月、末次随访时C2-7 cobb角、手术节段关节活动度(ROM)评价其对颈椎曲度和节段稳定性的影响。结果本组患者均顺利完成手术,手术时间56~82 min(平均65.7 min),术中出血量10~30 mL(平均20.7 mL)。所有患者均未发生组织感染、椎管内感染、硬膜撕裂、神经根损伤、麻醉围术期相关并发症等。所有患者均获随访,时间6~18个月(平均10.8个月)。术后1、3个月、末次随访时NDI评分(18.54%±3.06%、14.96%±2.33%、12.89%±2.33%)均显著低于术前(34.19%±3.83%),术后3个月、末次随访时NDI评分均显著低于术后1个月,差异均有统计学意义(P0.05)。术后1、3个月、末次随访时的颈椎JOA评分[(12.28±1.65)、(13.30±1.57)、(13.54±1.41)分]均显著高于术前[(9.25±1.49)分],差异有统计学意义(P0.05)。术前、术后1、3个月、末次随访时C2-7 cobb角、手术节段ROM比较,差异均无统计学意义(P>0.05)。末次随访时采用改良MacNab评分评价疗效:优9例,良5例,可1例。结论Delta大通道全内镜技术治疗脊髓型和神经根型颈椎病疗效良好,具有创伤小、并发症少、术后恢复快等优势,且不会影响颈椎曲度和节段稳定性。

关键词：颈椎椎板切除术减压术颈椎病 Delta大通道全内镜

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绝经后骨质疏松症与中医体质的相关性

中医杂志 2009年第8期50卷 696-698页

作者：孙益童培建肖鲁伟浙江中医药大学第一临床医学院浙江省杭州市滨江区滨文路310053

目的探讨绝经后骨质疏松症患者的体质分布特点及其与中医体质的相关性。方法采用流行病学病例对照设计,通过问卷调查法对绝经后骨质疏松症患者和正常人群进行体质分类及统计分析。结果两组人群的体质构成比有统计学差异(P<0.05),绝经后... 详细信息

目的探讨绝经后骨质疏松症患者的体质分布特点及其与中医体质的相关性。方法采用流行病学病例对照设计,通过问卷调查法对绝经后骨质疏松症患者和正常人群进行体质分类及统计分析。结果两组人群的体质构成比有统计学差异(P<0.05),绝经后骨质疏松症患者阳虚质、气虚质、阴虚质、瘀血质的构成比高于正常人群;不同程度、不同年龄段骨质疏松症患者的体质分布之间均存在统计学差异(P<0.05)。结论绝经后骨质疏松症患者主要体质类型为阳虚质,早期气虚质分布增加,晚期以阴虚质、瘀血质分布增加,这种规律与中医理论相一致。

关键词：骨质疏松症中医体质分型绝经

Expert consensus on elderly patients with hip fracture under epidemic of novel coronavirus pneumonia

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中华创伤杂志 2020年第2期36卷 104-110页

作者： Liu Guohui Liu Ximing tong Xiaoling Wang Dongliang Chen Yanxi Cao Liehu Liu Guodong Liu Jing Hu Yan Huang Biaotong Shi Zhongmin Zhang Dianying Hou Zhiyong Liu Hongjian tong peijian Song Shaojun Yang Lei Wang Yong Zhang Lei Luo Tao Wang Meitang Zhang Peng Zhang Yong Lin Haodong Yu Baoqing Mi Bobin Zhang Yingze Su Jiacan Department of Orthopedics Union Hospital of tongji Medical College Huazhong University of Science and Technology Wuhan 430000 China Central Theater General Hospital of PLA Outpatient Department Hankou Hospital Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai 200092 Zhongshan Hospital Affiliated to Fudan University Shanghai 200032 Department of Traumatic Orthopedics Changhai Hospital Affiliated to Naval Medical University Shanghai 200433 Department of Orthopedics Luodian Hospital Baoshan District Shanghai 201908 Medical Center of Trauma and War Injuries Daping Hospital Army Military Medical University Chongqing 400042 Institute of Translational Medicine Shanghai University Shanghai 200444 Sixth People''s Hospital Affiliated to Shanghai Jiaotong University Shanghai 200233 Peking University People''s Hospital Beijing 100035 Trauma Emergency Center Third Affiliated Hospital of Hebei Medical University Shijiazhuang 075061 First Affiliated Hospital of Zhengzhou University Wenzhou 450018 Zhejiang Provincial Hospital of Traditional Chinese Medicine Hangzhou 310003 Department of Emergency Second Affiliated Hospital of Wenzhou Medical University Wenzhou 325027 Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Wenzhou 325001 Putuo District Central Hospital Affiliated to Shanghai University of Chinese Medicine Shanghai 200062 Shanghai Public Health Clinical Center Shanghai 200083 Changhai Hospital Naval Medical University Shandong Provincial Hospital Jinan 250021 Tangdu Hospital Air Force Medical University Xi''an 710038 First Affiliated Hospital of Shanghai Jiaotong University Shanghai 200080 Pudong Hospital Fudan University Shanghai 201399

With the spread of novel coronavirus pneumonia (NCP) in December 2019, the management and rehabilitation of elderly patients with hip fractures and protection of medical staff face new challenges, and need to be adjusted appropriately under this very circumstances. Hip fractures in the elderly account for more than half of osteoporotic fractures. Expert group formulate this consensus so as to make better decision against this epidemic and protect patients'' families and medical staff. This consensus elaborates not only epidemic condition of NCP, but also general principles of medical admission, treatment and protection for both medical staff and patients, in order to provide some reference and promote the standardization of clinical diagnosis and treatment of elderly patients with hip fractures under the condition of NCP.

关键词： Aged Hip fractures Coronavirus infections Pneumonia Expert consensus

Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis

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Bone Research 2019年第3期7卷 286-295页

作者： Manli Tu Mi Yang Nanxi Yu Gehua Zhen Mei Wan Wenlong Liu Baochao Ji Hairong Ma Qiaoyue Guo peijian tong Li Cao Xianghang Luo Xu Cao Department of Orthopaedic Surgery The Johns Hopkins University School of Medicine Baltimore MD 21205 USA Department of Endocrinology The First Affiliated Hospital of Nanchang University 330006 Nanchang Jiangxi China Endocrinology Research Center of Xiangya Hospital Central South University 410008 Changsha Hunan China Department of Orthopedic Surgery The First Affiliated Hospital of Xinjiang Medical University 830054 Urumqi Xinjiang Uygur Autonomous Region China Department of Orthopedic Surgery The First Affiliated Hospital of Zhejiang Chinese Medical University 310006 Hangzhou Zhejiang Province China

Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.

关键词： pathogenesis rheumatoid arthritis transgenic

补肾活血汤含药血清干预体外培养大鼠骨髓间充质干细胞成软骨分化及补肾活血汤联合骨髓间充质干细胞治疗大鼠膝骨关节炎的实验研究

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中医正骨 2018年第1期30卷 6-11页

作者：吴刚童培建浙江中医药大学浙江杭州310053 浙江省中医院浙江杭州310006

目的:观察补肾活血汤含药血清对大鼠骨髓间充质干细胞(bone marrow stem cell,BMSC)成软骨分化的作用,及补肾活血汤联合BMSC治疗大鼠膝骨关节炎(knee osteoarthritis,KOA)的作用。方法:从4周龄SD大鼠股骨中分离培养BMSC,以8周龄SD大鼠... 详细信息

目的:观察补肾活血汤含药血清对大鼠骨髓间充质干细胞(bone marrow stem cell,BMSC)成软骨分化的作用,及补肾活血汤联合BMSC治疗大鼠膝骨关节炎(knee osteoarthritis,KOA)的作用。方法:从4周龄SD大鼠股骨中分离培养BMSC,以8周龄SD大鼠制备补肾活血汤含药血清和空白血清。选择体外培养的第3代BMSC,分为3组,分别加入含10%空白血清的DMEM培养液(空白组)、含10%空白血清的DMEM培养液及基础诱导液(诱导组)、含10%补肾活血汤含药血清的DMEM培养液及基础诱导液(含药血清组),干预后分别进行甲苯胺蓝染色、Ⅱ型胶原免疫组化染色,并以Real-time PCR法检测各组细胞中Ⅱ型胶原mRNA、聚集蛋白聚糖mRNA的水平。取18只8周龄SD大鼠,随机分为模型组、BMSC组及联合组,每组6只。通过切断右前交叉韧带对各组大鼠进行KOA造模。造模术后1周,向BMSC组与联合组大鼠右侧膝关节腔内注射5×10~6个·m L^(-1)BMSC-PBS溶液(每次0.1 m L,每周1次),向模型组大鼠右侧膝关节腔注射等量PBS溶液;联合组在关节腔注射的基础上每天以补肾活血汤灌胃(每次4 m L,每天1次)。干预8周后处死大鼠,取右侧膝关节软骨及软骨下骨组织,HE染色后在光学显微镜下观察。结果:干预7 d后,含药血清组细胞甲苯胺蓝染色呈阳性,细胞质呈蓝紫色;空白组和诱导组染色均为阴性。干预14 d后,含药血清组染色进一步加深,染色面积增大,呈明显的紫蓝色;空白组染色为阴性,诱导组可见少量蓝紫色染色。干预7 d、14 d后,Ⅱ型胶原免疫组化染色结果显示,空白组细胞均未见明显阳性染色,诱导组及含药血清组细胞胞浆和细胞间质内呈棕黄色或棕褐色染色,其中干预14 d后含药血清组细胞内染色深于诱导组。干预7 d后,3组大鼠BMSC中Ⅱ型胶原mRNA水平、聚集蛋白聚糖mRNA水平比较,组间差异均有统计学意义(1.02±0.23,1.33±0.11,2.11±0.23,F=47.181,P=0.000;1.03±0.32,1.36±0.16,1.93±0.10,F=26.508,P=0.000)。含药血清组的Ⅱ型胶原mRNA水平、聚集蛋白聚糖mRNA水平均高于空白组和诱导组(P=0.000,P=0.000;P=0.000,P=0.000),诱导组的Ⅱ型胶原mRNA水平、聚集蛋白聚糖mRNA水平均高于空白组(P=0.017;P=0.029)。药物干预8周后,模型组大鼠膝关节软骨表面粗糙,破坏严重,可见明显纤维增生;BMSC组软骨可见部分修复,表面仍较粗糙,细胞纤维化不明显;联合组关节软骨面光滑,软骨表面磨损不明显,无软骨表面纤维化。结论:补肾活血汤含药血清能有效促进体外培养的大鼠BMSC向软骨细胞分化;补肾活血汤灌胃联合BMSC膝关节腔内注射能有效防治KOA大鼠膝关节软骨破坏。

关键词：骨关节炎骨髓间质干细胞软骨,关节补肾活血汤大鼠动物实验