加减指迷茯苓方对胶原诱导性关节炎大鼠关节病变及滑膜VEGF/FLK-1 mRNA表达的影响

Effect of Modified Zhimi Fuling Formula(指迷茯苓方)on Arthropathy and Synovial VEGF/FLK-1 mRNA

目的:观察加减指迷茯苓方对胶原诱导性关节炎(CIA)大鼠关节病变及滑膜组织血管内皮生长因子(VEGF)和血管内皮生长因子受体(FLK-1)mRNA表达的影响,探讨加减指迷茯苓方对CIA的作用及其机制。方法:选用SPF级Wistar大鼠32只,随机选取8只作为空白对照组,其余24只采用尾根部及脊背部皮内注射牛Ⅱ型胶原乳化剂,7 d后加强免疫。造模成功后,将CIA大鼠随机分为模型对照组、雷公藤多苷组(7.81 mg·kg^(-1)灌胃)、加减指迷茯苓方组(31.68 g·kg^(-1)灌胃),每组8只。空白对照组和模型对照组大鼠灌服等体积的生理盐水。4组均连续灌胃30 d,每日1次。饲养期间测量大鼠体质量、踝关节肿胀度,治疗30 d后进行关节彩超评价,实时定量聚合酶链式反应法检测关节滑膜VEGF、FLI-1 mRNA水平。结果:与模型对照组比较,雷公藤多苷组和加减指迷茯苓方组大鼠关节炎指数评分、彩超超声表现分级(Szkudlarek)评分(关节积液、多普勒血流、滑膜增生、骨质侵蚀4个方面),以及关节滑膜的VEGF、FLK-1 mRNA表达水平均明显降低(P<0.01或P<0.05)。结论:加减指迷茯苓方可抑制CIA大鼠关节炎症,抑制滑膜VEGF和FLK-1表达。

Objective:To observe the effect of modified Zhimi Fuling Formula(指迷茯苓方)on arthropathy and synovial VEGF/FLK-1mRNA expression in collagen induced arthritis rats(CIA rats),and to explore the effect and mechanism of the formula on CIA.Methods:Thirty-two SPF Wistar rats were selected.Eight rats were randomly selected as the blank control group,and the other twenty-four were injected with bovine typeⅡcollagen emulsifier intradermally at the tail root and back of the spine.After 7 days of intensive immunization,CIA rats were randomly divided into a model control group,a tripterygium wilfordii polyglycosides group(TWP group with 7.81 mg·kg^(-1)gavage),and a modified Zhimi Fuling Formula group(MZFF group with 31.68 g·kg^(-1)gavage),with eight rats in each.The rats in the blank control group and the model control group were perfused with the same volume of normal saline.All the four groups were given gastric perfusion for 30 days,once a day.The body mass and ankle swelling of rats were measured during the feeding period.After 30 days of treatment,the joints were evaluated by color ultrasound,and the level of VEGF/FLI-1 mRNA in synovium of joints was detected by real-time quantitative PCR.Results:Compared with the model control group,the arthritis index score,Color Doppler Ultrasound Szkudlarek score(joint effusion,Doppler blood flow,synovial hyperplasia,bone erosion),and the expression level of VEGF/FLK-1 mRNA in the synovium of the rats in the TWP group and the MZFF group were significantly reduced(P<0.01 or P<0.05).Conclusion:Modified Zhimi Fuling Formula can inhibit joint inflammation and the expression of VEGF and FLK-1 in synovium of CIA rats.