膝关节骨性关节炎血清炎性因子与血管生成因子的关系
|
摘要
[目的]探讨膝关节骨性关节炎(KOA)患者血清炎性因子与碱性成纤维细胞生长因子(bFGF)、血管生成素-1 (Ang-1)、血管生成素-2 (Ang-2)的关系。[方法]选择2013年10月～2017年10月本科收治的70例KOA患者为KOA组,并选择同期年龄、性别相匹配的60例健康体检人群为健康组。采用酶联免疫吸附试验(ELISA)检测两组患者血清白介素-2 (IL-2)、白介素-6 (IL-6)、白介素-18 (IL-18)及bFGF、Ang-1、Ang-2水平的差异,Pearson相关分析之间的相关性。[结果]KOA组患者血清IL-2、IL-6、IL-18、bFGF、Ang-1、Ang-2水平显著高于健康组,差异有统计学意义(P<0.05)。70例膝关节骨性关节炎患者中,随K-L分级等级增加,血清IL-2、IL-6、IL-18、bFGF、Ang-1、Ang-2水平均有显著增加,不同等组K-L分级间差异有统计学意义(P<0.05),依次为Ⅲ级>Ⅱ级>Ⅰ级(P<0.05)。70例膝关节骨性关节炎患者的血清IL-2、IL-6、IL-18均与bFGF、Ang-1、Ang-2呈显著正相关(P<0.05); bFGF与Ang-1、Ang-2呈显著正相关(P<0.05); Ang-1与Ang-2呈显著正相关(P<0.05)。[结论]膝关节骨性关节炎患者血清炎性因子与血管生成相关因子水平高于正常健康组,且二者呈正相关,血清炎性因子可能参与了膝关节骨性关节炎新血管形成过程。
[Objective] To investigate the relationship between serum inflammatory factors and angiogenesis-factors, such as basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1) and angiopoietin-2(Ang-2) in knee osteoarthritis(KOA). [Methods] From October 2013 to October2017, 70 patients with KOA admitted to our hospital were included into this study as the KOA group, whereas 60 healthy persons with matching age and gender in the same period were selected as the healthy group. After blood sample harvested venously, the serum interleukin-2(IL-2), interleukin-6(IL-6), interleukin-18(IL-18), bFGF, Ang-1 and Ang-2 were measured by enzyme-linked immunosorbent assay(ELISA) in both groups. The Pearson correlation analysis was conducted among IL-2, IL-6, IL-18, bFGF, Ang-1 and Ang-2 in the KOA patients. [Results] The serum IL-2, IL-6, IL-18,, bFGF, Ang-1 and Ang-2 in the KOA group were significantly higher than those in the healthy group, which all proved statistically significant(P<0.05). Among the 70 patients with KOA, the serum IL-2, IL-6, IL-18, bFGF, Ang-1 and Ang-2 significantly increased as upgrading of Kellgren-Lawrence(K-L) scale, with significant differences among different K-L grades(P<0.05). Among the patients, the serum IL-2, IL-6, IL-18 were significantly positively correlated with the bFGF, Ang-1 and Ang-2(P<0.05), while the bFGF was significantly positively correlated to the Ang-1 and Ang-2(P<0.05) and.the Ang-1 was positively correlated to the Ang-2(P<0.05). [Conclusions] The levels of serum inflammatory factors and angiogenesis factors in the patients with knee osteoarthritis were higher than the healthy persons. The inflammatory factors are considerably positively correlated to the angiogenesis factors in KOA, which suggests that serum inflammatory factors might be involved in the new blood vessels formation in pathogenesis of knee osteoarthritis.
[Objective] To investigate the relationship between serum inflammatory factors and angiogenesis-factors, such as basic fibroblast growth factor(bFGF), angiopoietin-1(Ang-1) and angiopoietin-2(Ang-2) in knee osteoarthritis(KOA). [Methods] From October 2013 to October2017, 70 patients with KOA admitted to our hospital were included into this study as the KOA group, whereas 60 healthy persons with matching age and gender in the same period were selected as the healthy group. After blood sample harvested venously, the serum interleukin-2(IL-2), interleukin-6(IL-6), interleukin-18(IL-18), bFGF, Ang-1 and Ang-2 were measured by enzyme-linked immunosorbent assay(ELISA) in both groups. The Pearson correlation analysis was conducted among IL-2, IL-6, IL-18, bFGF, Ang-1 and Ang-2 in the KOA patients. [Results] The serum IL-2, IL-6, IL-18,, bFGF, Ang-1 and Ang-2 in the KOA group were significantly higher than those in the healthy group, which all proved statistically significant(P<0.05). Among the 70 patients with KOA, the serum IL-2, IL-6, IL-18, bFGF, Ang-1 and Ang-2 significantly increased as upgrading of Kellgren-Lawrence(K-L) scale, with significant differences among different K-L grades(P<0.05). Among the patients, the serum IL-2, IL-6, IL-18 were significantly positively correlated with the bFGF, Ang-1 and Ang-2(P<0.05), while the bFGF was significantly positively correlated to the Ang-1 and Ang-2(P<0.05) and.the Ang-1 was positively correlated to the Ang-2(P<0.05). [Conclusions] The levels of serum inflammatory factors and angiogenesis factors in the patients with knee osteoarthritis were higher than the healthy persons. The inflammatory factors are considerably positively correlated to the angiogenesis factors in KOA, which suggests that serum inflammatory factors might be involved in the new blood vessels formation in pathogenesis of knee osteoarthritis.
引文
[1]孙先润,吕龙宝,唐涛,等.大黄酸对猕猴骨关节炎IL-1β、NO/iNOS表达的影响[J].中国矫形外科杂志,2018,26(15):1413-1417.
[2]Bar ORD,Rael LT,Thomas GW,et al.Inflammatory pathways in knee osteoarthritis:potential targets for treatment[J].Curr Rheumatol Rev,2015,154(3):476-483.
[3]聂华翎,郑毅.类风湿关节炎患者血清血管生成素样蛋白3血管生成素样蛋白4水平及临床意义[J].中华风湿病学杂志,2016,20(2):112-115.
[4]黄娴倩,陈勇,陈立斌,等.类风湿关节炎患者血清血管内皮生长因子血管生成素-1和2的检测及其与关节滑膜病变的相关性研究[J].中华风湿病学杂志,2012,16(10):679-683.
[5]LC Barroso,GS Magalhaes,I Galv?o,et al.Angiotensin-(1-7)promotes resolution of neutrophilic inflammation in a model of antigen-induced arthritis in mice[J].Frontiers Immunol,2017,8:1596.
[6]Zhao M,Yu Z,Li Z,et al.Expression of angiogenic growth factors VEGF,bFGF and ANG1 in colon cancer after bevacizumab treatment in vitro:a potential self-regulating mechanism[J].Oncology Reports,2017,37(1):601.
[7]Rufaihah AJ,Johari NA,Vaibavi SR,et al.Dual delivery of VEGFand ANG-1 in ischemic hearts using an injectable hydrogel[J].Acta Biomaterialia,2017,48(1):58-67.
[8]马胜利.膝骨关节炎患者血清炎性因子与血管生成相关因子的关系[J].新乡医学院学报,2016,33(7):626-628.
[9]Wang F,Luo Y,Li C,et al.Correlation between deregulated expression of PER2 gene and degree of glioma malignancy[J].Tumori,2014,1 00(6):e266-e272.
[10]刘贵艳,边森,李芳,等.骨髓间充质干细胞移植对胶原诱导关节炎大鼠血清及关节滑膜中白细胞介素-22及基质金属蛋白酶-3表达的影响[J].中华医学杂志,2017,97(9):698-702.
[11]Ahmed AS,Gedin P,Hugo A,et al.Activation of NF-κB in synovium versus cartilage from patients with advanced knee osteoarthritis:a potential contributor to inflammatory aspects of disease progression[J].J Immunol,2018,201(7):1918-1927.
[12]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):38602-38617.
[13]Fu Z,Liu P,Yanq D,et al.Interleukin-18-induced inflammatory responses in synoviocytes and chondrocytes from osteoarthritic patients[J].Int J Mol Med,2012,30(4):805-810.
[14]Ishikawa Y,Qi A,Nakagawa J,et al.Gait analysis of patients with knee osteoarthritis by using elevation angle:confirmation of the planar law and analysis of angular difference in the approximate plane[J].Advanced Robotics,2016,31(1-2):68-79.
[15]El-Fetiany AE,Kassem EM,El-Barbary AM,et al.Evaluation of plasma basic fibroblast growth factor(bFGF)in primary knee osteoarthritis patients[J].Egyptian Rheumatol,2017,39(1):33-37.
[16]Heijink A,Gomoll AH,Madry H,et al.Biomechanical considerations in the pathogenesis of osteoarthritis of the knee[J].Knee Surg Sports Traumatol Arthros,2016,24(7):2313-2318.
[17]Tasaki Y,Shimizu M,Inoue N,et al.Disruption of vascular endothelial homeostasis in systemic juvenile idiopathic arthritis-associated macrophage activation syndrome:The dynamic roles of angiopoietin-1 and-2[J].Cytokine,2016,80(1):1.
[18]A?ikalin?,B?lükba?i Hatip FF,Tan RF,et al.Effect of Angiotensin-(1-7)on Aortic Response,TNF-α,IL-1βand Receptor for Advanced Glycation Endproduct in Rat's Adjuvant-Induced Arthritis[J].Pharmacology,2016,97(5-6):207.
[19]Tan AW,Liau LL,Chua KH,et al.Enhanced in vitro angiogenic behaviour of human umbilical vein endothelial cells on thermally oxidized TiO2 nanofibrous surfaces[J].Sci Rep,2016,6:21828.
[20]Wan J,Wan H,Yang R,et al.Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats[J].J Ethnopharmacol,2018,211:348-357.
[21]Li Y,Zhang P,Liu Y,et al.Helium preconditioning protects the brain against hypoxia/ischemia injury via improving the neurovascular niche in a neonatal rat model[J].Behavioural Brain Res,2016,314:165-172.
[22]Falcon BL,Chintharlapalli S,Uhlik MT,et al.Antagonist antibodies to vascular endothelial growth factor receptor 2(VEGFR-2)as anti-angiogenic agents[J].Pharmacol Therap,2016,164:204-225.
[2]Bar ORD,Rael LT,Thomas GW,et al.Inflammatory pathways in knee osteoarthritis:potential targets for treatment[J].Curr Rheumatol Rev,2015,154(3):476-483.
[3]聂华翎,郑毅.类风湿关节炎患者血清血管生成素样蛋白3血管生成素样蛋白4水平及临床意义[J].中华风湿病学杂志,2016,20(2):112-115.
[4]黄娴倩,陈勇,陈立斌,等.类风湿关节炎患者血清血管内皮生长因子血管生成素-1和2的检测及其与关节滑膜病变的相关性研究[J].中华风湿病学杂志,2012,16(10):679-683.
[5]LC Barroso,GS Magalhaes,I Galv?o,et al.Angiotensin-(1-7)promotes resolution of neutrophilic inflammation in a model of antigen-induced arthritis in mice[J].Frontiers Immunol,2017,8:1596.
[6]Zhao M,Yu Z,Li Z,et al.Expression of angiogenic growth factors VEGF,bFGF and ANG1 in colon cancer after bevacizumab treatment in vitro:a potential self-regulating mechanism[J].Oncology Reports,2017,37(1):601.
[7]Rufaihah AJ,Johari NA,Vaibavi SR,et al.Dual delivery of VEGFand ANG-1 in ischemic hearts using an injectable hydrogel[J].Acta Biomaterialia,2017,48(1):58-67.
[8]马胜利.膝骨关节炎患者血清炎性因子与血管生成相关因子的关系[J].新乡医学院学报,2016,33(7):626-628.
[9]Wang F,Luo Y,Li C,et al.Correlation between deregulated expression of PER2 gene and degree of glioma malignancy[J].Tumori,2014,1 00(6):e266-e272.
[10]刘贵艳,边森,李芳,等.骨髓间充质干细胞移植对胶原诱导关节炎大鼠血清及关节滑膜中白细胞介素-22及基质金属蛋白酶-3表达的影响[J].中华医学杂志,2017,97(9):698-702.
[11]Ahmed AS,Gedin P,Hugo A,et al.Activation of NF-κB in synovium versus cartilage from patients with advanced knee osteoarthritis:a potential contributor to inflammatory aspects of disease progression[J].J Immunol,2018,201(7):1918-1927.
[12]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):38602-38617.
[13]Fu Z,Liu P,Yanq D,et al.Interleukin-18-induced inflammatory responses in synoviocytes and chondrocytes from osteoarthritic patients[J].Int J Mol Med,2012,30(4):805-810.
[14]Ishikawa Y,Qi A,Nakagawa J,et al.Gait analysis of patients with knee osteoarthritis by using elevation angle:confirmation of the planar law and analysis of angular difference in the approximate plane[J].Advanced Robotics,2016,31(1-2):68-79.
[15]El-Fetiany AE,Kassem EM,El-Barbary AM,et al.Evaluation of plasma basic fibroblast growth factor(bFGF)in primary knee osteoarthritis patients[J].Egyptian Rheumatol,2017,39(1):33-37.
[16]Heijink A,Gomoll AH,Madry H,et al.Biomechanical considerations in the pathogenesis of osteoarthritis of the knee[J].Knee Surg Sports Traumatol Arthros,2016,24(7):2313-2318.
[17]Tasaki Y,Shimizu M,Inoue N,et al.Disruption of vascular endothelial homeostasis in systemic juvenile idiopathic arthritis-associated macrophage activation syndrome:The dynamic roles of angiopoietin-1 and-2[J].Cytokine,2016,80(1):1.
[18]A?ikalin?,B?lükba?i Hatip FF,Tan RF,et al.Effect of Angiotensin-(1-7)on Aortic Response,TNF-α,IL-1βand Receptor for Advanced Glycation Endproduct in Rat's Adjuvant-Induced Arthritis[J].Pharmacology,2016,97(5-6):207.
[19]Tan AW,Liau LL,Chua KH,et al.Enhanced in vitro angiogenic behaviour of human umbilical vein endothelial cells on thermally oxidized TiO2 nanofibrous surfaces[J].Sci Rep,2016,6:21828.
[20]Wan J,Wan H,Yang R,et al.Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats[J].J Ethnopharmacol,2018,211:348-357.
[21]Li Y,Zhang P,Liu Y,et al.Helium preconditioning protects the brain against hypoxia/ischemia injury via improving the neurovascular niche in a neonatal rat model[J].Behavioural Brain Res,2016,314:165-172.
[22]Falcon BL,Chintharlapalli S,Uhlik MT,et al.Antagonist antibodies to vascular endothelial growth factor receptor 2(VEGFR-2)as anti-angiogenic agents[J].Pharmacol Therap,2016,164:204-225.