桃红四物汤对类风湿关节炎模型大鼠关节肿胀改善效果及机制研究  

Study on Improvement Effect of Taohong Siwu Decoction on Joint Swelling in Rat Models with Rheumatoid Arthritis and Its Mechanism

作　　者：范卫闯 吕立桃 白登彦 马富海[3] FAN Weichuang;LYU Litao;BAI Dengyan;MA Fuhai

机构地区：[1]开封市人民医院骨一科,河南开封475002 [2]甘肃省第二人民医院骨科,甘肃兰州730015 [3]甘肃省中医院骨科,甘肃兰州730050

出　　处：《新中医》2023年第1期53-57,共5页New Chinese Medicine

基　　金：甘肃省自然科学基金项目(21CX1RA176);甘肃省中医药管理局课题(GZK-2016-53)。

摘　　要：目的:观察桃红四物汤改善类风湿关节炎(RA)模型大鼠关节肿胀的效果并探讨其作用机制。方法:从75只雌性SPF级Wistar大鼠中随机选取60只,建立RA大鼠模型,剩余15只纳入空白组。将造模成功的60只大鼠随机分为模型组及桃红四物汤低、中、高(6.53、13.06、26.13 g/kg)剂量组,每组15只。连续给药4周。采用关节炎指数(AI)评分法评定各组大鼠右肢的肿胀情况;酶联免疫吸附法测定各组大鼠血清基质金属蛋白酶-8 (MMP-8)和基质金属蛋白酶组织抑制剂-3 (TIMP-3)含量;苏木精-伊红染色法观察各组大鼠滑膜组织病理学变化情况;采用蛋白质印迹法检测各组大鼠关节滑膜中Toll样受体4 (TLR4)、核转录因子-κB (NF-κB)蛋白含量。结果:干预后,与空白组比较,模型组大鼠AI评分、血清MMP-8含量及关节滑膜TLR4、NF-κB蛋白含量均显著升高(P<0.05),血清TIMP-3含量降低(P<0.05);与模型组比较,桃红四物汤低、中、高剂量组大鼠AI评分、血清MMP-8含量及关节滑膜TLR4、NF-κB蛋白含量降低(P<0.05),血清TIMP-3含量升高(P<0.05)。与空白组比较,模型组大鼠关节滑膜组织出现炎性细胞浸润,滑膜细胞增生;干预后,桃红四物汤低、中、高剂量组大鼠关节滑膜组织病理变化得到明显改善。结论:桃红四物汤能有效缓解RA大鼠关节肿胀症状,减轻炎症反应,其机制与下调TLR4/NF-κB信号通路蛋白表达,降低MMP-8含量和提高TIMP-3含量有关。Objective:To observe the effect of Taohong Siwu Decoction on the improvement of joint swelling in rat models with rheumatoid arthritis(RA) and discuss its mechanism. Methods:With a total of75 female SPF Wistar rats,60 rats were selected as rat models with RA,and the rest of 15 rats were included into the blank group. After successful modeling,a total of 60 rats were randomly divided into the model group and the Taohong Siwu Decoction groups of low-dose,medium-dose and high-dose(6.53 g/kg,13.06 g/kg and 26.13 g/kg),with 15 rats in each group. All groups were administrated for four weeks. The swelling of right limbs of rats in each group was evaluated by Arthritis Index(AI) scoring;the contents of matrix metalloproteinase-8(MMP-8) and tissue inhibitor of metalloproteinase-3(TIMP-3) were measured by enzyme-linked immunosorbent assay;the pathological changes of synovial tissue of joints of rats in each group were observed by hematoxylin-eosin staining;the protein contents of Toll-like receptor 4(TLR4) and nuclear factor-κB(NF-κB) of the synovial tissue of joints of rats in each group were detected by Western blot. Results:After intervention,the scores of AI,MMP-8 content,and protein contents of TLR4 and NF-κB in the model group were significantly increased when compared with those in the blank group(P<0.05), and the TIMP-3 content was decreased(P<0.05);compared with those in the model group,the scores of AI,MMP-8 content and protein contents of TLR4 and NF-κB in the Taohong Siwu Decoction groups of low-dose,medium-dose and high-dose were decreased(P<0.05),and the TIMP-3content was increased(P<0.05). Compared with those in the blank group,the inflammatory cells infiltration and synovial cell proliferation were found in the synovial tissue of joints of rats in the model group;after intervention,the pathological changes of the synovial tissue of joints of rats in the Taohong Siwu Decoction groups of low-dose, medium-dose and high-dose were significantly improved. Conclusion: Taohong Siwu Decoction can effectively im

关 键 词：类风湿关节炎 桃红四物汤 Toll样受体4/核转录因子-κB 基质金属蛋白酶-8 基质金属蛋白酶组织抑制剂-3 

分 类 号：R684.3[医药卫生—骨科学]