通痹颗粒对胶原性关节炎大鼠RANKL/RANK/OPG系统及MMP-3、TIMP-1表达的影响  

Effects of Tongbi Granules(通痹颗粒)on RANKL/RANK/OPG System,MMP-3 and TIMP-1 in Collagen-Induced Arthritis Rats

作　　者：柳玉佳[1] 欧慧萍 吴伊莹[1] 王莘智[1] 范伏元[1] LIU Yu-jia;OU Hui-ping;WU Yi-ying;WANG Shen-zhi;FAN Fu-yuan(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Hunan 410007,China;Hunan Traditional Chinese Medical College,Zhuzhou Hunan 412012,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药高等专科学校,湖南株洲412012

出　　处：《中医药导报》2021年第10期22-26,48,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省自然科学基金项目(2020JJ5434);湖南省教育厅科研项目(19C1446);湖南省卫生健康委科研项目(202103101094);湖南中医药大学校级科研基金项目(2018XJJJ41)。

摘　　要：目的:探究通痹颗粒对胶原性关节炎(CIA)大鼠RANKL/RANK/OPG系统及MMP-3、TIMP-1表达的影响。方法:将60只健康雌性SD大鼠随机分成空白组、模型组、雷公藤多苷组、通痹颗粒低剂量组和通痹颗粒高剂量组,每组12只。除空白组外,其余各组用牛Ⅱ型胶原诱导CIA模型。造模成功后,空白组和模型组予等量生理盐水灌胃,其余各组分别以雷公藤多苷片、低剂量通痹颗粒和高剂量通痹颗粒灌胃,1次/d,连续给药2周。行关节炎指数评分和关节肿胀度测量,并检测各组滑膜病理学情况,RANKL、RANK、OPG的mRNA和蛋白表达情况,以及血清中MMP-3、TIMP-1水平。结果:时间与组别的交互效应对CIA大鼠关节炎指数评分和关节肿胀度的影响差异均有统计学意义(P<0.05),雷公藤多苷组、通痹颗粒低剂量组和通痹颗粒高剂量组大鼠关节炎指数评分和关节肿胀度均低于模型组(P<0.05),治疗第14天通痹颗粒高剂量组改善情况优于雷公藤多苷组(P<0.05);模型组大鼠滑膜重度增生,并可见缺损及血管翳形成,雷公藤多苷组、通痹颗粒低剂量组和通痹颗粒高剂量组大鼠滑膜病变有所改善,雷公藤多苷组和通痹颗粒高剂量组优于通痹颗粒低剂量组;与模型组比较,雷公藤多苷组、通痹颗粒低剂量组和通痹颗粒高剂量组大鼠滑膜组织中RANKL、RANK的mRNA和蛋白的表达均明显降低(P<0.05),OPG mRNA和蛋白的表达量均明显升高(P<0.05),且通痹颗粒高剂量组优于雷公藤多苷组(P<0.05);与模型组比较,雷公藤多苷组、通痹颗粒低剂量组和通痹颗粒高剂量组大鼠血清中MMP-3、TIMP-1水平明显降低(P<0.05),且通痹颗粒高剂量组优于雷公藤多苷组(P<0.05)。结论:通痹颗粒可减轻CIA大鼠的滑膜炎症,并对关节破坏具有一定的缓解作用,提示经由RANKL/RANK/OPG系统的调节作用并有效平衡血清中MMP-3、TIMP-1的异常表达,可能是通痹颗粒治疗CIA的机制之一。Objective:To observe the effect of Tongbi Granule on RANKL/RANK/OPG system and the expression of MMP-3 and TIMP-1 in rats of collagenic arthritis(CIA).Methods:Totally 60 healthy female SD rats were randomly divided into blank group,model group,tripterygium wilfordii polyglycoside group,Tongbi Granule low-dose group and Tongbi Granule high-dose group,12 rats in each group.Except the blank group,the rest group were induced into CIA rats model with bovine collagen typeⅡ.After successful modeling,the blank group and model group were given the same amount of normal saline by gavage,and the remaining groups were gavage with tripterygium polyglycoside tablets,low-dose Tongbi Granules and high-dose Tongbi Granules respectively,once a day for two consecutive weeks.The arthritis index score and joint swelling were measured,and the pathology of the synovium was observed in each group.The expression of RANKL,RANK,OPG genes and proteins,and the levels of MMP-3 and TIMP-1 were detected.Results:The interaction effect of time and group showed statistical significance on the arthritis index score and joint swelling of CIA rats(P<0.05).The tripterygium wilfordii polyglycoside group,Tongbi Granule low-dose group and Tongbi Granule high-dose group showed lower arthritis index score and joint swelling than model group(P<0.05),and the high-dose Tongbi Granules group showed better improvement than tripterygium wilfordii polyglycoside group on the 14th day of treatment(P<0.05).The model group showed severe synovial hyperplasia,synovial defect and pannus formation.Synovial lesions have been improved in tripterygium wilfordii polyglycoside group,Tongbi Granule low-dose group and Tongbi Granule high-dose group,and the tripterygium wilfordii polyglycoside group and Tongbi Granule high-dose group showed better improvement than Tongbi Granule low-dose group.Compared with model group,the mRNA and protein expressions of RANKL and RANK in synovial tissue of rats significantly decreased in tripterygium wilfordii polyglycoside group,Tongbi Granu

关 键 词：胶原性关节炎 通痹颗粒 RANKL/RANK/OPG系统 基质金属蛋白酶-3 基质金属蛋白酶抑制剂-1 大鼠 

分 类 号：R285.5[医药卫生—中药学]