沙利度胺对类风湿关节炎模型大鼠炎症及血管新生相关因子的影响

Effect of Thalidomide on Inflammation and Angiogenesis Related Factors in Rheumatoid Arthritis Rats

目的探讨沙利度胺(thalidomide,Thd)对Ⅱ型胶原诱导的关节炎(CIA)模型大鼠的治疗作用,并探讨其可能的作用机制。方法将雌性Sprague-Dawley大鼠30只随机分为空白组、模型组和Thd治疗组各10只。模型组和Thd治疗组采用Ⅱ型胶原制备CIA模型。造模次日开始,Thd治疗组灌胃给予Thd150mg.kg-1.d-1,空白组及模型组灌胃给予0.9%氯化钠溶液15mL.kg-1,均给药6周。治疗过程中对大鼠的关节炎症程度进行评分,治疗后对大鼠右后足进行放射学评分,免疫组化方法检测3组大鼠滑膜组织微血管密度(MVD),WesternBlot法检测大鼠血清血管内皮生长因子(VEGF)、基质金属蛋白酶(MMP)-1,2,3,9活性。结果与空白组比较,模型组大鼠血清VEGF、MMP-1,2,3,9活性表达均明显升高。与模型组比较,Thd治疗组大鼠关节炎症指数、放射学和滑膜组织MVD均明显下降(P<0.05或P<0.01)。结论Thd能改善CIA大鼠关节炎症症状和放射学改变,并可能通过降低大鼠血清VEGF、MMP-1,2,3,9表达而发挥抑制关节滑膜血管新生作用。

Objective To investigate the therapeutic effect and mechanism of thalidomide （Thd） on type Ⅱ collagen induced arthritis of rats. Methods 30 female SD rats were randomly divided into control, model and Thd treatment groups. CIA model was induced by type Ⅱ collagen. Thd group was treated with Thd 150 mg · kg^-1 the day after model establishment, and the control and model groups were administered with normal saline 15 mL · kg^-1 ,for 6 weeks. Severity of joint inflammation was scored during the treatment and right metapedes were scored by radiology technique post-treatment. The microvessel density （MVD） of synovium was detected by immunohistochemistry method, the active expression of VEGF and matrix metalloproteinase-1,2, 3, 9 in serum were tested by Western Blot assy. Results The active expression of VEGF and MMP-1,2, 3, 9 in blood vessels of model group obviously increased compared with the normal control group; meanwhile, the inflammatory arthropathy index, radiological and synovium histopathology changes in thalidomide-treated rats were all conspicuously decreased compared with those in the model group （P 〈 0.05 or P 〈 0.01 ）. Conclusion Thalidomide can remarkably improve arthritis symptoms and radiographic changes of CIA rats. It could inhibit synovium angiogenesis by down-regulating expression of VEGF and MMP-1, 2, 3, 9.