青藤碱对兔膝骨关节炎模型组织形态学及关节液炎性细胞和聚集蛋白聚糖酶含量的影响
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摘要
目的观察不同剂量青藤碱对兔膝骨关节炎(OA)模型关节软骨和滑膜组织形态学及关节液白细胞介素(IL)-6、IL-17及聚集蛋白聚糖酶(ADAMTS)-4、ADAMTS-5含量的影响。方法采用Hulth法建立OA模型。将50只新西兰大白兔随机分为空白组、模型组和青藤碱低、中、高剂量组。空白组不予任何处理,模型组给予生理盐水、给药组给予盐酸青藤碱注射液膝关节腔注射,共干预10次,青藤碱给药量分别为0.2 mL(5 mg)、0.35 mL(8.75 mg)和0.5 mL(12.5 mg)。干预结束后取关节软骨行番红O染色,取滑膜组织行HE染色,进行组织学评分;ELISA检测关节液IL-6、IL-17、ADAMTS-4和ADAMTS-5含量。结果模型组软骨Mankin’s评分和滑膜组织病理学评分显著高于空白组(P<0.01),青藤碱中、高剂量组软骨Mankin’s评分和滑膜评分显著低于模型组(P<0.05,P<0.01);模型组关节液IL-6、IL-17、ADAMTS-4和ADAMTS-5含量较空白组显著升高(P<0.01),青藤碱中、高剂量组关节液IL-6、IL-17、ADAMTS-4和ADAMTS-5含量较模型组显著降低(P<0.05,P<0.01)。结论中、高剂量青藤碱对OA模型病变软骨具有保护作用。
Objective To observe the effects of different concentrations of sinomenine(SIN) on morphology of synovium and cartilage and contents of IL-6, IL-17, ADAMT-4 and ADAMT-5 in synovial fluid of rabbit knee osteoarthritis model. Methods After establishing the knee osteoarthritis model by Hulth method, the New Zealand white rabbits were randomly divided into control group, model group, SIN low-, medium-and high-dosage groups.Control group did not receive any treatment. Model group and other administration group received saline and SIN knee joint injection, for 10 times. The dosages of SIN were 0.2 mL(5 mg), 0.35 mL(8.75 mg), and 0.5 mL(12.5 mg),respectively. After intervention, the articular cartilage was stained with Safranin O, and the synovium was taken for HE staining and histological scoring. The levels of IL-6, IL-17, ADAMTS-4 and ADAMTS-5 in joint fluid were detected by ELISA. Results Mankin's scores of articular cartilage and histological scores of synovium in model group were significantly higher than control group(P<0.01), and the Mankin's score and synovial score in SIN medium-and high-dosage groups were significantly lower than those in the model group(P<0.05, P<0.01). The levels of IL-6,IL-17, ADAMTS-4 and ADAMTS-5 in the model group were significantly higher than those in the control group(P<0.01). The levels of IL-6, IL-17, ADAMTS-4 and ADAMTS-5 in SIN medium-and high-dosage groups were significantly lower than those in the model group(P<0.05, P<0.01). Conclusion SIN medium and high dosage can delay the degradation of articular cartilage of osteoarthritis model.
Objective To observe the effects of different concentrations of sinomenine(SIN) on morphology of synovium and cartilage and contents of IL-6, IL-17, ADAMT-4 and ADAMT-5 in synovial fluid of rabbit knee osteoarthritis model. Methods After establishing the knee osteoarthritis model by Hulth method, the New Zealand white rabbits were randomly divided into control group, model group, SIN low-, medium-and high-dosage groups.Control group did not receive any treatment. Model group and other administration group received saline and SIN knee joint injection, for 10 times. The dosages of SIN were 0.2 mL(5 mg), 0.35 mL(8.75 mg), and 0.5 mL(12.5 mg),respectively. After intervention, the articular cartilage was stained with Safranin O, and the synovium was taken for HE staining and histological scoring. The levels of IL-6, IL-17, ADAMTS-4 and ADAMTS-5 in joint fluid were detected by ELISA. Results Mankin's scores of articular cartilage and histological scores of synovium in model group were significantly higher than control group(P<0.01), and the Mankin's score and synovial score in SIN medium-and high-dosage groups were significantly lower than those in the model group(P<0.05, P<0.01). The levels of IL-6,IL-17, ADAMTS-4 and ADAMTS-5 in the model group were significantly higher than those in the control group(P<0.01). The levels of IL-6, IL-17, ADAMTS-4 and ADAMTS-5 in SIN medium-and high-dosage groups were significantly lower than those in the model group(P<0.05, P<0.01). Conclusion SIN medium and high dosage can delay the degradation of articular cartilage of osteoarthritis model.
引文
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[5]郑洁,王瑞辉,寇久社.青藤碱关节腔注射对膝骨关节炎兔软骨和滑膜组织形态学及基质金属蛋白酶-13和软骨寡聚基质蛋白的影响[J].中国中医药信息杂志,2016,23(1):74-77.
[6]熊元,赵振国,李传郡,等.兔膝骨关节炎模型的制备及鉴定[J].实验动物科学,2013,30(3):31-34,63.
[7]MANKIN H J,DORFMAN H,LIPPIELLO L,et al.Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hipsⅡ.Correlation of morphology with biochemical and metabolic data[J].Bone Joint Surg,1971,53(3):523-531.
[8]PRITZKER K P,GAY S,JIMENEZ S A,et al.Osteoarthritis cartilage histopathology:grading and staging[J].Osteoarthritis Cartilage,2006,14(1):13-29.
[9]GOLDRING M B.Articular cartilage degradation in osteoarthritis[J].HSS Journal,2012,8(1):7-9.
[10]KLEIN T,BISCHOFF R.Active metalloproteases of the ADisintegrin and Metalloprotease(ADAM)family:biological function and structure[J].J Proteome Res,2011,10(1):17-33.
[11]AKESON G,MALEMUD C J.A role for soluble IL-6 receptor in osteoarthritis[J].J Funct Morphol Kinesiol,2017,2(3):27.
[12]KOSHY P J,HENDERSON N,LOGAN C,et al.Interleukin17 induces cartilage collagen breakdown:novel synergistic effects incombination with proinflammatory cytokines[J].Annals of the Rheumatic Diseases,2002,61(8):704-713.
[13]LIU Y S,PENG H,MENG Z,et al.Correlation of IL-17 level in synovia and severity of knee osteoarthritis[J].Med Sci Monit,2015,21:1732-1736.
[14]KIM Y G,PARK J W,LEE J M,et al.IL-17 inhibits osteoblast differentiation and bone regeneration in rat[J].Archives of oral biology,2014,59(9):897-905.
[15]KOTAKE S,UDAGAWA N,TAKAHASHI N,et al.IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis[J].The Journal of Clinical Investigation,1999,103(9):1345-1352.
[16]MORT J S,GENG Y Q,FISHER W D,et al.Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis[J].BMCMusculoskeletal Disorders,2016,17:89.
[17]曹吉慧,赵桂森,冯延江.青风藤的化学成分与药理作用[J].国外医药:植物药分册,2008,23(2):62-66.
[2]KRASNOKUTSKY S,BELISKAYA-LEVY I,BENCARDINO J,et al.Quantitative magnetic resonance imaging evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis[J].Arthritis Rheum,2011,63(10):2983-2991.
[3]SCANZELLO C,PLAAS A,CROW M.Innate immune system activation in osteoarthritis:is osteoarthritis a chronic wound[J].Curr Opin Rheumatol,2008,20(5):565-572.
[4]ROEMER F,GUERMAZI A,FELSON D,et al.Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up:the MOSTstudy[J].Ann Rheum Dis,2011,70(10):1804-1809.
[5]郑洁,王瑞辉,寇久社.青藤碱关节腔注射对膝骨关节炎兔软骨和滑膜组织形态学及基质金属蛋白酶-13和软骨寡聚基质蛋白的影响[J].中国中医药信息杂志,2016,23(1):74-77.
[6]熊元,赵振国,李传郡,等.兔膝骨关节炎模型的制备及鉴定[J].实验动物科学,2013,30(3):31-34,63.
[7]MANKIN H J,DORFMAN H,LIPPIELLO L,et al.Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hipsⅡ.Correlation of morphology with biochemical and metabolic data[J].Bone Joint Surg,1971,53(3):523-531.
[8]PRITZKER K P,GAY S,JIMENEZ S A,et al.Osteoarthritis cartilage histopathology:grading and staging[J].Osteoarthritis Cartilage,2006,14(1):13-29.
[9]GOLDRING M B.Articular cartilage degradation in osteoarthritis[J].HSS Journal,2012,8(1):7-9.
[10]KLEIN T,BISCHOFF R.Active metalloproteases of the ADisintegrin and Metalloprotease(ADAM)family:biological function and structure[J].J Proteome Res,2011,10(1):17-33.
[11]AKESON G,MALEMUD C J.A role for soluble IL-6 receptor in osteoarthritis[J].J Funct Morphol Kinesiol,2017,2(3):27.
[12]KOSHY P J,HENDERSON N,LOGAN C,et al.Interleukin17 induces cartilage collagen breakdown:novel synergistic effects incombination with proinflammatory cytokines[J].Annals of the Rheumatic Diseases,2002,61(8):704-713.
[13]LIU Y S,PENG H,MENG Z,et al.Correlation of IL-17 level in synovia and severity of knee osteoarthritis[J].Med Sci Monit,2015,21:1732-1736.
[14]KIM Y G,PARK J W,LEE J M,et al.IL-17 inhibits osteoblast differentiation and bone regeneration in rat[J].Archives of oral biology,2014,59(9):897-905.
[15]KOTAKE S,UDAGAWA N,TAKAHASHI N,et al.IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis[J].The Journal of Clinical Investigation,1999,103(9):1345-1352.
[16]MORT J S,GENG Y Q,FISHER W D,et al.Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis[J].BMCMusculoskeletal Disorders,2016,17:89.
[17]曹吉慧,赵桂森,冯延江.青风藤的化学成分与药理作用[J].国外医药:植物药分册,2008,23(2):62-66.