补肾活血方加减对膝骨关节炎大鼠模型疼痛及软骨损伤的影响In fluence of Bushen Huoxue Decoction on Pain and Cartilage Injury in Rat Models with Knee Osteoarthritis
李胜,刘魏,季卫锋,钟莹,童培建
摘要(Abstract):
目的探索补肾活血方加减对膝骨关节炎大鼠模型疼痛及软骨损伤的影响。方法取50只SD大鼠,随机分为空白组,模型组,补肾活血方加减低、中、高剂量组,每组10只。空白组不造模,余4组用碘乙酸向大鼠双侧膝关节注射进行KOA造模。造模后第2天,补肾活血方加减低、中、高剂量组SD大鼠分别予低、中、高剂量补肾活血方加减进行灌胃,空白组、模型组予0.9%生理盐水灌胃,连续灌胃4周。分别于造模后第2天和第4周测定各组大鼠的压痛值和热痛阈值。第4周痛阈值测定结束后处死大鼠,取双侧膝关节进行组织病理学观察并评定Mankin′s评分。结果灌胃4周后,与模型组比较,补肾活血方低、中、高剂量组大鼠压痛及热痛阈值较模型组均有提高,除补肾活血方低剂量组大鼠热痛阈值与模型组比较无差异性(P>0.05),余各组间比较皆有明显差异性(P<0.05),其中以高剂量组提高最为明显,中剂量次之,低剂量最末。大鼠膝关节软骨番红染色结果示,与空白组比较,模型组大鼠软骨表面缺损严重,软骨基质染色明显减轻、不均,而补肾活血方低、中、高剂量组的病理变化逐渐减轻,各组大鼠膝关节软骨Mankin′s评分结果显示,与模型组比较,各组大鼠Mankin′s评分均较低,补肾活血方低、中、高剂量组大鼠Mankin′s评分比较有明显差异性(P<0.05),且呈剂量依赖性。结论补肾活血方加减能提高KOA模型大鼠疼痛阈值,修复软骨损伤,并与剂量呈正相关。
关键词(KeyWords): 补肾活血方加减;膝骨关节炎;SD大鼠;动物实验
基金项目(Foundation): 全国中医药传承博士后培养-中管局(2A61603财【2016】063号-01);; 浙江省科技厅重大科技专项社会发展项目(2014C03035);; 浙江省自然科学基金(LQ18H270003)
作者(Author): 李胜,刘魏,季卫锋,钟莹,童培建
参考文献(References):
- [1]Brooks PM.The burden of musculoskeletal disease-a global perspective[J].Clin Rheumatol,2006,25(6):778-781.
- [2]Kongtharvonskul J,Anothaisintawee T,Mce-voy M,et al.Efficacy and safely of glucosamine,diacerein,and NSAIDs in osteoarthritis knee:a systematic review and network metaanalysia[J].Med Res,2015,20(1):24.
- [3]Pomonis JD,Boulet JM,Gottshall SL,et al.Development and pharmacological characterization of a rat model of osteoarthritis pain[J].Pain,2005,114:339-346.
- [4]魏伟,吴希美,李元建.药理实验方法学[M].北京:人民卫生出版社,2010.1721.
- [5]Krampla WW,Newrla SP,Kroener AH,et al.Changes on magnetic resonance tomography in the knee joints of marathon runner:a 10-year longitudinal study[J].Skeletal Radiol,2008,37(7):619-626.
- [6]Stoppiello L,Mapp P,Wilson D,et,al.Structural associaations of symptomatic knee asteoarthritis[J].Arthritis Rheumatol,2014,2066(2011):3018-2017.
- [7]Laslett L,Kingsbury S,Hensor E,et al.Effect of bisphosphonate use in patients with symptomaticand radiographic knee osteoarthritis:data from the osteoarthritis initiative[J].Ann Rheum Dis,2014,2073:824-830.
- [8]Clegg D,Reda D,Harris C,et al.Glucosamine,chondroitin sulfate,and the two in combination for painfu lknee osteoarthritis[J].N Engle J Med,2006,2354:795-808.
- [9]Fransen M,Agaliotis M,Nairn L,et al.Glucosamine and chondroitin for knee osteoarthritis:a double-blind randomized placebo-controlled clincal trial evaluating single and combination regimens[J].Ann Rheum Dis,2015,2074:851-888.
- [10]李兆福,狄朋桃.昆明市膝骨关节炎中医症候研究[J].中医正骨,2014,26(6):24-27.
- [11]郭跃,杨青梅,鲁超,等.膝骨关节炎的中医症候特点研究[J].中医临床研究,2015,7(4):1-4.
- [12]向珍蛹,茅建春.膝骨关节炎中医证候分布的流行病学研究[J].上海中医药杂志,2012,46(12):5-8.
- [13]Pelletier JP,Di Battista JA,Routhley P,et al.Cytokines and inflammation in carilage degradation[J].Rheum Dis Clin North Am,1993,19(3):545-568.
- [14]Man lukazewski.Osteoarthritis,current and future management options[J].Arthitis&rhaenatism,2002,24:151-154.
- [15]肖志锋,王德刚,许传勇,等.补肾活血方对Wnt/β-catenin信号通道介导的人滑膜细胞与正常软骨细胞共培养体系的调控作用[J].中国中医骨伤科杂志,2016,24(4):1-6.