帕瑞昔布对膝骨关节炎大鼠关节软骨及软骨下骨的影响Effect of parecoxib on articular cartilage and subchondral bone in the rat model of knee osteoarthritis
钟培瑞;周君;廖源;孙光华;刘静;伍琦;周桂娟;廖瑛;
摘要(Abstract):
[目的]观察帕瑞昔布对膝骨关节炎大鼠关节软骨、软骨下骨及自噬标志物Beclin-1表达的影响。[方法] 30只雄性SD大鼠随机分为假手术组、模型组、治疗组。假手术组仅切开膝关节皮肤,模型组与治疗组应用Hulth法复制OA模型。治疗组自术后首天起腹腔注射帕瑞昔布[10 mg/(kg·d)],每周5次,连续12周。12周后处死大鼠,ELISA法检测血清IL-1、IL-6、CTX-Ⅰ、CTX-Ⅱ、TRACP-5b;关节软骨行HE、番红O染色及Mankin评分;Micro-CT扫描软骨下骨;RT-QPCR技术检测Beclin-1 mRNA表达量。[结果]模型组IL-1、IL-6、CTX-Ⅰ、CTX-Ⅱ、TRACP-5b水平高于假手术组(P<0.05);治疗组IL-1、IL-6、CTX-Ⅱ水平低于模型组(P<0.05)。治疗组Mankin评分低于模型组(P<0.05)。与假手术组比较,模型组骨体积分数(BV/TV)、骨小梁量(Tb.N)显著降低(P<0.05),而骨小梁分离度(Tb.Sp)显著增高(P<0.05)。与模型组比较,治疗组骨体积分数(BV/TV)、骨小梁量(Tb.N)降低(P<0.05),而骨小梁分离度Tb.Sp增高(P<0.05)。治疗组Beclin-1 mRNA表达量高于假手术组与模型组(P<0.05)。[结论]帕瑞昔布可改善OA大鼠关节软骨退变,其机制可能是通过增强细胞自噬来完成。并能促进大鼠软骨下骨骨量丢失,可能给OA治疗带来负面影响。
关键词(KeyWords): 骨关节炎;自噬;关节软骨;软骨下骨
基金项目(Foundation): 国家自然科学基金资助项目(编号:81674045);; 湖南省自然科学基金项目(编号:2017JJ3272);; 湖南省教育厅优秀青年项目(编号:17B232);; 湖南省卫计委课题(编号:B20180062)
作者(Author): 钟培瑞;周君;廖源;孙光华;刘静;伍琦;周桂娟;廖瑛;
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参考文献(References):
- [1]Giunta S, Castorina A, Marzagalli R, et al. Ameliorative effects of PACAP against cartilage degeneration. morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis[J]. Int J Molecular Sci, 2015, 16(3):5922-5944.
- [2]Lamark T, Johansen T. Aggrephagy:selective disposal of protein aggregates by macroautophagy[J]. Int J Cell Biol, 2012, 2012:736905.
- [3]Wong E, Cuervo AM. Integration of clearance mechanisms:the proteasome and autophagy[J]. Cold Spring Harbor Perspect in Biol, 2010, 2(12):a006734.
- [4]Caramés B, Taniguchi N, Otsuki S, et al. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis[J]. Arthritis Rheumatology,2010, 17(3):S109-S109.
- [5]Zhang G, Cao J, Yang E, et al. Curcumin improves age-related and surgically induced osteoarthritis by promoting autophagy in mice[J]. Biosci Rep, 2018, 38(4).
- [6]Benderdour M, Martel-Pelletier J, Pelletier JP, et al. Cellular aging, senescence and autophagy processes in osteoarthritis[J]. Curr Aging Sci, 2015, 8(2):1-10.
- [7]张晨,马骏,党晓谦,等.非甾体抗炎药治疗骨关节炎的研究进展[J].中华关节外科杂志(电子版), 2017, 11(2):66-69.
- [8]Wang Z, Zheng C, Zhong Y, et al. Interleukin-17 can induce osteoarthritis in rabbit knee joints similar to hulth'smethod[J]. Bio Med Res Int, 2017(12):2091325.
- [9]Mankin HJ, Dorfman H, Lippiello L, et al. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data[J]. J Bone Joint Surg Am, 1971, 53(3):523-537.
- [10]Lane N E, Shidara K, Wise B L. Osteoarthritis year in review 2016:clinical[J]. Osteoarthritis Cartilage, 2017, 25(2):209-215.
- [11]Aho O M, Finnil?M, Thevenot J, et al. Subchondral bone histology and grading in osteoarthritis[J]. Plos One, 2017, 12(3):e0173726.
- [12]Tang X, Wang S, Zhan S, et al. The prevalence of symptomatic knee osteoarthritis in china:results from the china health and retirement longitudinal study[J]. Arthritis Rheumatology, 2016, 68(3):648-653.
- [13]薛庆云,王坤正,裴福兴,等.中国40岁以上人群原发性骨关节炎患病状况调查[J].中华骨科杂志, 2015, 35(12):1206-1212.
- [14]中华医学会骨科学分会关节外科学组.骨关节炎诊疗指南(2018年版)[J].中华骨科杂志,2018,38(1):21-27.
- [15]Li Y S, Xiao W F, Luo W. Cellular aging towards osteoarthritis[J].Mechanisms Ageing Development, 2017, 162:80-84.
- [16]Jilka RL, O'Brien CA. The role of osteocytes in age-related bone loss[J]. Curr Osteoporos Rep, 2016, 14(1):16-25.
- [17]Blaney Davidson E N, van Caam A P, Pm V D K. Osteoarthritis year in review 2016:biology[J]. Osteoarthritis Cartilage, 2017,25(2):175.
- [18]Zhang Y, Vasheghani F, Li Y, et al. Cartilage-specific deletion of mTOR upregulates autophagy and protects mice from osteoarthritis.[J]. Ann Rheumatic Dis, 2015, 74(7):1432.
- [19]Chen CH, Chang LH, Kang L, et al. Parathyroid hormone(1-34)ameliorated knee osteoarthritis in rats via autophagy[J]. J Applied Physiol, 2018, 124(5):2017-2021.
- [20]Takahama M, Akira S, Saitoh T. Autophagy limits activation of the inflammasomes[J]. Immunol Rev, 2018, 281(1):62.
- [21]Hügle T, Geurts J. What drives osteoarthritis?-synovial versus subchondral bone pathology[J]. Rheumatology(Oxford), 2016,21:254-261.
- [22]李能,廖瑛,廖源,等.伊班膦酸钠对大鼠膝骨关节炎关节软骨及软骨下骨的影响[J].中国骨质疏松杂志, 2017, 23(1):78-83.
- [23]Barr AJ, Campbell TM, Hopkinson D, et al. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis[J]. Arthritis Res Ther, 2015, 17:228.
- [24]Borgeat A, Ofner C, Saporito A, et al. The effect of nonsteroidal anti-inflammatory drugs on bone healing in humans:a qualitative,systematic review[J]. J Clin Anesthesia, 2018, 49:92-100.