摘要
目的:探讨萆薢分清饮对急性痛风性关节炎(acute gouty arthritis,AGA)模型大鼠的影响及作用机制。方法:雄性SD大鼠随机分为空白组、模型组、萆薢分清饮组(23.33 g/kg)、秋水仙碱组(0.3 mg/kg),每组10只,预防性给药,每日1次,连续7 d。灌胃给药第5天,空白组除外,踝关节注射单钠尿酸盐混悬液制备AGA模型。造模后测定踝关节肿胀度、步态评分及炎症指数评分;H&E染色观察踝关节滑膜组织病理学变化,ELISA法测定血清炎性因子及ROS水平;生化法测定血清MDA、GSH水平,SOD、CAT活性;实时荧光定量PCR测定踝关节滑膜组织NLRP3、ASC mRNA表达水平;Western blot检测NF‑κB/NLRP3通路相关蛋白表达。结果:与空白组比较,模型组大鼠踝关节明显肿胀(P<0.01),步态评分和炎症指数评分显著增加(P<0.01),H&E染色滑膜组织增生,大量炎性细胞浸润,组织病理评分升高(P<0.01),血清IL‑6、IL‑1β、TNF‑α、ROS及MDA水平升高(P<0.05),SOD、GSH、CAT水平降低(P<0.01),滑膜组织NLRP3、ASC mRNA表达及p‑NF‑κB p65/NF‑κB p65、NLRP3、ASC、cleaved Caspase‑1蛋白表达显著升高(P<0.01);与模型组比较,萆薢分清饮组踝关节肿胀度、步态评分及炎症指数评分显著降低(P<0.05),滑膜组织增生与炎性细胞浸润减轻,组织病理评分降低(P<0.01),血清IL‑1β、IL‑6、TNF‑α及ROS、MDA水平显著降低(P<0.05),SOD、GSH水平升高(P<0.01),滑膜组织NLRP3、ASC mRNA表达及p‑NF‑κB p65/NF‑κB p65、NLRP3、ASC、cleaved Caspase‑1蛋白表达水平降低(P<0.05)。结论:萆薢分清饮可能通过抑制AGA大鼠NF‑κB/NLRP3信号通路改善炎症状态。
Objective:To explore the therapeutic impact and mechanism of Bixie Fenqing Decoction on acute gouty arthritis(AGA)model rats.Methods:Male SD rats were randomly assigned to the blank group,model group,Bixie Fenqing Decoction group(23.33 g/kg)and colchicine group(0.3 mg/kg),10 rats per group.The rats received preventive treatment daily for a period of 7 days.On the 5th day of gavage,the AGA model was induced by injecting monosodium urate suspension into ankle except the blank group.The swelling degree,gait and inflammatory index score of ankle joint were measured after modeling.The histopathological changes of ankle synovium were examined using H&E staining,the levels of serum inflammatory factors and ROS were detected by ELISA.Serum MDA and GSH levels,SOD and CAT activities were detected by biochemical method.Real‑time fluorescence quantitative PCR was used to detect NLRP3 and ASC mRNA expression levels within the ankle synovial tissue.The expression of related proteins in the NF‑κB/NLRP3 pathway was detected by Western blot.Results:In contrast to the blank group,ankle joint of rats in the model group exhibited markedly increased swelling(P<0.01),demonstrated notably higher scores in both gait assessment and inflammatory indices(P<0.01).After H&E staining,synovial tissue hyperplasia was prominently observed,a large amount of inflammatory cell infiltrated,and histopathological scoring indicated an increase(P<0.01).The levels of IL‑6,IL‑1β,TNF‑α,ROS,and MDA in serum were increased(P<0.05),SOD,GSH,and CAT were decreased(P<0.01).In the synovial tissue,there was a upregulation of NLRP3 and ASC mRNA,and increased expression of p‑NF‑κB p65/NF‑κB p65,NLRP3,ASC and cleaved Caspase‑1 protein(P<0.01).Compared to the model group,ankle swelling,gait score and inflammatory index score in the Bixie Fenqing Decoction group were significantly decreased(P<0.05),synovial tissue hyperplasia and inflammatory cell infiltration were decreased,and histopathologic score were decreased(P<0.01).Serum IL‑1β,IL‑6,TNF‑α,ROS and MDA were significantly decreased(P<0.05),SOD and GSH levels were increased(P<0.01).mRNA expressions of NLRP3 and ASC and protein expression levels of p‑NF‑κB p65/NF‑κB p65,NLRP3,ASC,and cleaved Caspase‑1 were decreased in synovial tissues(P<0.05).Conclusion:The Bixie Fenqing Decoction may exert its anti‑inflammatory effects in AGA rats through inhibiting the NF‑κB/NLRP3 signaling pathway.
作者
张靖
韩真真
王思宇
苏培培
邵灿灿
李晓冰
何小鹃
郭洪涛
ZHANG Jing;HAN Zhenzhen;WANG Siyu;SU Peipei;SHAO Cancan;LI Xiaobing;HE Xiaojuan;GUO Hongtao(Department of Rheumatology,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;The First Clinical Medical College,Henan University of Chinese Medicine,Zhengzhou 450046,China;Traditional Chinese Medicine(Zhongjing)School,Henan University of Chinese Medicine,Zhengzhou 450046,China;Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《海南医科大学学报》
北大核心
2025年第22期1696-1704,共9页
Journal of Hainan Medical University
基金
国家自然科学基金(82274342)
河南省中医药传承与创新人才工程(仲景工程)中医药学科拔尖人才项目(CZ0325‑13)
河南省中医药科学研究专项项目(2023ZXZX1145)
河南省卫生健康委国家中医临床研究基地科研专项(2022JDZX091)
河南省科技攻关项目(252102311259)。
