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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 study the effect of promoting blood circulation and removing blood stasis of clearing heat and promoting blood circulation and to explore the mechanism of this prescription inhibiting angiogenesis in synovial tissue. Methods The rat model of type Ⅱ collagen-induced arthritis (CIA) was used. The treatment group was treated with Qingre Huoxue Fang large and small dose intervention. Compared with normal group, model group and positive drug group, Degree, pathological section of the joint, synovial pathological section, microvessel density (MVD), serum inflammatory cytokines (INF) -γ and vascular diseases related indicators of tissue-type plasminogen activator (t PA) Effect of nitric oxide synthase (eNOS). Results Qingre Huoxue prescription can obviously relieve joint swelling in CIA rats. The pathological sections of arthritis showed that Qingre Huoxue prescription can inhibit synovial hyperplasia and delay the destruction of articular cartilage and bone. Synovial pathological sections showed that the infiltration of inflammatory cells in the synovial tissue of the large and small doses of Qingre Huoxue group decreased compared with the model group, and the microvessel density was lower than that of the model group. The serum INF-γ Compared with the model group, the content was significantly decreased (P <0.05). Compared with model group, Qingre Huoxue Fang high-dose group can reduce t PA generation (P <0.05); Compared with model group, Qingre Huoxue Fang low dose group can down-regulate e NOS expression (P <0.05) Significantly down-regulated the expression of eNOS (P <0.01), indicating that this prescription has an inhibitory effect on eNOS expression and is dose-dependent. Conclusion In addition to clearing heat and promoting blood circulation can effectively control the inflammation of the joints, delaying the destruction of cartilage and bone in the joints and reducing synovial hyperplasia in joints, it can also improve the blood stasis around the joints and inhibit the expression of pro-angiogenic factors, thus reducing The number of neovasculature, better control of active rheumatoid arthritis condition.