清热活血方抑制Ⅱ型胶原诱导型关节炎大鼠滑膜组织血管新生的研究  

Inhibition of Qingre Huoxue decoction on synovial angiogenesis in rat model of type Ⅱ collagen-induced arthritis

作　　者：刘鹏霄[1,2] 曹炜[1] 姜泉[1] 吴振宇[1] 吴广均[1] 杨卉[1] 王清林[2] 郜亚茹 智恺 

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学

出　　处：《北京中医药大学学报》2014年第10期686-690,I0002,共6页Journal of Beijing University of Traditional Chinese Medicine

基　　金：北京市自然科学基金资助项目(No.7132223)

摘　　要：目的研究清热活血方的活血化瘀作用,探讨该方药抑制滑膜组织内血管新生的机制。方法采用Ⅱ型胶原诱导型关节炎(CIA)大鼠模型,治疗组用清热活血方大、小剂量干预,同正常组、模型组、阳性药物组比较,观察清热活血方对CIA大鼠关节肿胀度、关节病理切片、滑膜病理切片、微血管密度(MVD)、血清中致炎因子干扰素(INF)-γ及血管疾病相关指标组织型纤溶酶原激活因子(t PA)、内皮型一氧化氮合酶(e NOS)的影响。结果清热活血方能明显缓解CIA大鼠关节肿胀;关节病理切片显示清热活血方可以抑制关节内滑膜的增生,延缓关节软骨与骨的破坏。滑膜病理切片显示,清热活血方大、小剂量组滑膜组织内炎症细胞的浸润较模型组减少,且微血管密度较模型组降低;清热活血方大、小剂量组大鼠血清中INF-γ含量较模型组明显减少(P<0.05)。与模型组比较,清热活血方大剂量组可以减少t PA的生成(P<0.05);与模型组比较,清热活血方小剂量组可以下调e NOS的表达(P<0.05),大剂量组能显著下调e NOS的表达(P<0.01),说明该方对于e NOS表达具有抑制作用,并且呈剂量相关性。结论清热活血除了可以有效地控制关节的炎症,延缓关节内软骨与骨的破坏,减少关节内滑膜的增生外,还可以改善关节周围血瘀的情况,抑制促血管生成因子的表达,从而减少新生血管的数量,较好地控制活动期类风湿关节炎的病情。Objective To investigate the underlying mechanism of Qingre Huoxue decoction （QRHXD） in inhibiting synovial angiogenesis through observing its effects of promoting blood circulation and removing blood stasis. Methods Rat model of type II collagen-induced arthritis （CIA） was taken as the study object. Overall 50 SD rats were divided into 5 groups： normal group, model group, positive drug （LY294002） group, QRHXD low-dose group （low-dose group） and QRHXD high-dose group（high-dose group）. Volume of paw swelling, pathological sections of the ankle joints and synovial tissue and microvessel density （MVD） were observed. In addition, the serum content of interferon （ INF）-γ, endothelial nitric oxide synthase （eNOS） and tissue plasminogen activator （tPA） were measured by EIJSA. Results QRHXD significantly alleviated paw swelling in CIA rats. Pathological sections showed that QRHXD alleviated synovial hyperplasia, articular cartilage and bone destruction in joint, as well as decreased inflammatory ceils infiltration and MVD in synovial tissue. Compared with model group, expression levels of INF-γ in both QRHXD groups were decreased significantly （P 〈 0.05 ） ; release of tPA in high-dose group was decreased significantly （P 〈 0.05 ） ; expression of eNOS was down-regulated both in low-dose group （ P 〈 0.05 ） and high-dose group （ P 〈 0.01 ）. Conclusion QRHXD has a satisfactory therapeutic effect on active rheumatoid arthritis through relieving the inflammation of arthritis, synovial proliferation and articular cartilage and bone destruction.

关 键 词：类风湿关节炎 清热活血方 血管新生 大鼠 

分 类 号：R285.5[医药卫生—中药学]