仙鹿健骨汤对膝骨性关节炎大鼠关节软骨损伤的修复作用及机制研究Repairing Effect and Mechanism of Xianlu Jiangu Decoction on Articular Cartilage Injury in Rats with Knee Osteoarthritis
袁宝明,冯学会,李宇能
摘要(Abstract):
目的观察仙鹿健骨汤对膝骨性关节炎(KOA)大鼠关节软骨损伤的修复作用并探讨其机制。方法 SD大鼠100只,根据体质量随机分成5组:对照组、模型组、仙鹿健骨汤各剂量组;模型组、仙鹿健骨汤各剂量组构建KOA大鼠关节软骨损伤模型,并于造模成功第1天开始给予相应药物灌胃,持续给予3个月,对照组和模型组给予等体积0.9%氯化钠注射液。试验结束后,测定大鼠膝骨性骨关节炎软骨Mankin′s评分、p38m RNA、NF-κB mRNA、p38、NF-κB、MMP-9、MMP-13、IL-1β蛋白水平。结果与对照组比较,模型组、仙鹿健骨汤各剂量组KOA软骨Mankin′s评分、p38、NF-кB mRNA、蛋白表达水平、MMP-9、MMP-13、IL-1β蛋白表达水平明显升高(P <0.05);与模型组比较,仙鹿健骨汤各剂量组KOA软骨Mankin′s评分、p38、NF-κB mRNA、蛋白表达水平、MMP-9、MMP-13、IL-1β蛋白表达水平明显降低(P <0.05),且随着仙鹿健骨汤给药剂量的增加,KOA软骨Mankin′s评分、p384、NF-κB mRNA、蛋白表达水平、MMP-9、MMP-13、IL-1β蛋白表达水平逐渐降低,剂量-效应关系明显(P <0.05)。结论仙鹿健骨汤能明显减轻软骨细胞损伤程度,对KOA关节软骨损伤具有一定程度的修复作用,其机制与仙鹿健骨汤组能通过抑制炎症信号通路p38、NF-κB m RNA、蛋白表达水平的表达进而抑制细胞因子MMP-9、MMP-13、IL-1β的表达有关。
关键词(KeyWords): 膝骨性关节炎;关节软骨损伤;仙鹿健骨汤;p384;NF-κB;大鼠
基金项目(Foundation): 北京市科学技术委员会科研计划项目(D161100005913009)
作者(Author): 袁宝明,冯学会,李宇能
参考文献(References):
- [1] Niu J,Clancy M,Aliabadi P,et al. Metabolic Syndrome,Its components,and knee osteoarthritis:the framingham osteoarthritis study[J]. Arthritis&Rheumatology,2017,69(6):1194-1203.
- [2] Kraus VB,Collins JE,Hargrove D,et al. Predictive validity of biochemical biomarkers in knee osteoarthritis:data from the FNIH OA Biomarkers Consortium[J]. Annals of the Rheumatic Diseases,2017,76(1):186-187.
- [3] Duymus TM,Mutlu S,Dernek B,et al. Choice of intra-articular injection in treatment of knee osteoarthritis:platelet-rich plasma,hyaluronic acid or ozone options[J]. Knee Surgery Sports Traumatology Arthroscopy,2017,25(2):1-8.
- [4] Lin J,Wang S,Orthopedics DO. Clinical study of Jintiange capsules in the prevention and treatment of the knee osteoarthritis via P38-MAPK signal pathway[J]. Chinese Journal of Osteoporosis,2014,6(2):54-56.
- [5] Wei HE,Boning LI,Tongsheng LI,et al. Experimental study of the therapeutic mechanism of Jiangu recipe in the treatment of knee osteoarthritis[J]. Chinese Journal of Osteoporosis,2016,228(3):108-109.
- [6] Liu YX,Wang GD,Wang X,et al. Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis:an in vivo and in vitro study[J]. Oncotarget,2017,8(24):54-56.
- [7] Xinping SU,Zhu K,Tan X,et al. Expression of IKKαand NF-κB mRNA for zhitongjiangu recipe on cartilage of knee osteoarthritis[J]. Chinese Journal of Traditional Medical Traumatology&Orthopedics,2017,9(3):41-42.
- [8] Yu X,Zhao L,Yu Z,et al. Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model[J]. Experimental&Therapeutic Medicine,2017,14(2):1531-1537.
- [9] Lou F,Yuan S,Jia H,et al. Effect of gutong powder on the expression of IL-1β,TNF-αand MMP-3 in the patients with knee osteoarthritis[J]. Clinical Journal of Traditional Chinese Medicine,2017,9(2):89-91.
- [10] Zhang SN,Ouyang LZ,Wang XZ,et al. Effect of acupuncture plus thunder-fire moxibustion on MMP-3, TIMP-1 and TGF-β1 in rats with knee osteoarthritis[J].针灸推拿医学:英文版,2017,15(5):322-327.
- [11]吴剑静,康孟乐,王靖,等.仙鹿健骨汤含药血清对成骨细胞矿化结节及BMP-2表达影响的实验研究[J].浙江中医杂志,2010,45(2):103-105.
- [12]吴剑静,王靖,吴云刚,等.仙鹿健骨汤含药血清对成骨细胞增殖和ALP影响的实验研究[J].浙江中医药大学学报,2009,33(1):36-37.
- [13]吴剑静.仙鹿壮骨汤对去势大鼠骨质疏松症防治效果及机制探讨[D].上海:上海中医药大学,2007.
- [14] Lin J,Chen B,Long M,et al. Effect of serum containing tortoise shell glue and deer-horn glue on the expression of JNK and p38 MAPK Gene in osteoarthritis chondrocytes of guinea pigs[J]. Chinese Journal of Traditional Medical Traumatology&Orthopedics,2016,6(2):45-48.
- [15] Shi J,Zhang C,Yi Z,et al. Explore the variation of MMP3,JNK,p38 MAPKs,and autophagy at the early stage of osteoarthritis[J]. Iubmb Life,2016,68(4):293-302.
- [16] Guo Y,Min Z,Jiang C,et al. Downregulation of HS6ST2 by miR-23b-3p enhances matrix degradation through p38MAPK pathway in osteoarthritis[J]. Cell Death&Disease,2018,9(6):56-58.
- [17] Hai-Qun LI,Zhang ZS,Bo LI,et al. Effects of medical ozone water on the expression of p38MAPK、ERK and JNK in articular cartilage of rabbits with knee osteoarthritis[J]. Progress of Anatomical Sciences,2018,9(2):56-59.
- [18] Tan B,Liu J,Zhang P,et al. Xing Feng capsule alleviates hypercoagulable state in knee osteoarthritis patients by inhibiting NF-κB signaling pathway[J]. Immunological Journal,2016,6(2):54-55.
- [19] Bao H,Yiqun LI,Feng WU,et al. Effect of buyang huanwu decoction on WOMAC scores and TNF-α,PGE2 and MMP-3in joint fluid of knee osteoarthritis patients[J]. Journal of Guangzhou University of Traditional Chinese Medicine,2016,9(3):47-49.
- [20] Wei W,Yongli WU,Chun LI,et al. Effects of sini decoction cake moxibustion on serum IL-1,IL-6 and TNF-αlevels in knee osteoarthritis of rabbits[J]. Liaoning Journal of Traditional Chinese Medicine,2017,6(4):47-49.