沙利度胺及氨甲蝶呤抗CIA大鼠滑膜血管新生及其作用机制的研究

被引:11
作者
张育
周玮
顾健
梁虹
沈维干
薛永骥
马莉
机构
[1] 扬州大学临床医学院血液风湿科
关键词
沙利度胺; 氨甲喋呤; 大鼠; 关节炎; 胶原诱导型; 血管新生;
D O I
暂无
中图分类号
R96 [药理学];
学科分类号
100706 [药理学];
摘要
目的研究沙利度胺、氨甲蝶呤对大鼠Ⅱ型胶原诱导型关节炎血管新生的影响及相关的机制。方法建立类风湿性关节炎大鼠模型.自造模次日治疗组分别给予沙利度胺、甲氨蝶呤和沙利度胺联合甲氨蝶呤治疗,在第6周取膝关节应用免疫组化检测其滑膜的微血管密度(MVD),取血清进行Western Blot检测大鼠体内血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-1、2、3、9的表达并计算相对含量。结果①免疫组织化学染色显示沙利度胺、氨甲蝶呤和沙利度胺联合氨甲蝶呤治疗模型大鼠可使关节滑膜中新生血管数量明显减少.微血管密度(MVD)明显降低(P<0.05).以沙利度胺联合氨甲蝶呤组作用最强。②沙利度胺、氨甲蝶呤和沙利度胺联合氨甲蝶呤可抑制VEGF、MMP-1、2、3、9表达(P均<0.05)。结论沙利度胺和氨甲蝶呤可能通过抑制VEGF,MMP-1、2、3、9的表达而发挥抗滑膜血管新生的作用,且两者有协同作用。
引用
收藏
页码:23 / 27+32 +32
页数:6
相关论文
共 7 条
[1]
Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction [J].
Clavel, Gaeelle ;
Bessis, Natacha ;
Lemeiter, Delphine ;
Fardellone, Patrice ;
Mejjad, Othmane ;
Menard, Jean-Francois ;
Pouplin, Sophie ;
Boumier, Patrick ;
Vittecoq, Olivier ;
Le Loeet, Xavier ;
Boissier, Marie-Christophe .
CLINICAL IMMUNOLOGY, 2007, 124 (02) :158-164
[2]
VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: Results of an immunohistochemical study [J].
Simonetti, O. ;
Lucarini, G. ;
Goteri, G. ;
Zizzi, A. ;
Biagini, G. ;
Lo Muzio, L. ;
Offidani, A. .
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 2006, 19 (04) :751-760
[3]
The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis [J].
Litinsky, I ;
Paran, D ;
Levartovsky, D ;
Wigler, I ;
Kaufman, I ;
Yaron, I ;
Yaron, M ;
Caspi, D ;
Elkayam, O .
CYTOKINE, 2006, 33 (02) :106-110
[4]
Thalidomide as a novel therapeutic agent: new uses for an old product [J].
Teo, SK ;
Stirling, DI ;
Zeldis, JB .
DRUG DISCOVERY TODAY, 2005, 10 (02) :107-114
[5]
IL-17, IL-1β and TNF-α stimulate VEGF production by dedifferentiated chondrocytes [J].
Honorati, MC ;
Cattini, L ;
Facchini, A .
OSTEOARTHRITIS AND CARTILAGE, 2004, 12 (09) :683-691
[6]
Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction?: A clinical, radiological, and pathological study in 12 patients monitored for 10 years [J].
Latour, F ;
Zabraniecki, L ;
Dromer, C ;
Brouchet, A ;
Durroux, R ;
Fournié, B .
JOINT BONE SPINE, 2001, 68 (06) :493-498
[7]
Target molecules for anti-angiogenic therapy: from basic research to clinical trials [J].
Hagedorn, M ;
Bikfalvi, A .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2000, 34 (02) :89-110