Upper limb arthromyodynia can be treated with Notopterygium by down-regulating P2X3 to mediate PKC-induced inflammatory response  

羌活通过调节P2X3抑制PKC诱导的炎症反应治疗“上肢痹痛”

作　　者：Yingzheng Wang Ce Yang Cuiping Zhu Qianqian Zhao Xuehua Lu Xiaoyu Su Yinghao Wang 王颖峥;杨策;朱翠萍;赵茜茜;卢雪花;苏晓宇;王英豪(福建中医药大学药学院,福建福州350122;重庆三峡医药高等专科学校,重庆404120;福建省医学科学研究院,福建福州350001)

机构地区：[1]College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China [2]Medical school,Chongqing Three Gorges Medical College,Chongqing 404120,China [3]Fujian Academy of Medical Sciences,Fuzhou 350001,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2022年第3期163-175,共13页中国药学（英文版）

基　　金：The Department of Science&Technology of Fujian Province(Grant No.2017J01539 and 2020J01729);the Education Department Of Fujian Province(Grant No.JAT190239).

摘　　要：Rheumatoid arthritis(RA)is one of the most common refractory diseases in the world,and traditional Chinese medicine Notopterygium(NE)has been used in the treatment of upper limb pain for a long time.NE can significantly reduce the expression of inflammatory pain target P2X3 receptor in rats with upper-limb arthritis.To verify the relationship between the mechanism of NE for“upper limb paralysis”and the P2X3 receptor-mediated PKC inflammatory response pathway,UPLC was taken to measure the exact medicinal substance of ethyl acetate from NE.Sprague Dawley rats were randomly divided into a blank group,a model group,a live-action group,and a positive group.The joint cavity was removed after 21 d.Moreover,a model group,a live group,and a positive group were also set up with RA-FLS cells in our in vitro study.The expressions of P2X3 and PKC inflammation pathway indicators were detected by Western blotting analysis.A P2X3 inhibitor(A-317491)acted on RA-FLS cells,and a model group and a positive group were set.Then the protein expression of PKC was detected.NE reduced the expressions of P2X3,Rab7,PKC,and NF-κB at the protein level in both systems.NE and P2X3 receptor antagonists reduced the expressions of key proteins in the PKC pathway in RA-FLS cells to similar extents,and their effects were not additive.NE could effectively improve the“forelimb pain”of RA rats,with a mechanism closely related to the P2X3/Rab7/PKC/NF-κB pathway.类风湿性关节炎(RA)是世界上最难以治愈的疾病之一。中药羌活(NE)常用于治疗上肢疼痛。NE可显著降低上肢关节炎大鼠炎性疼痛靶点P2X3受体的表达。为了验证NE治疗“上肢痹痛”的机制与P2X3受体介导的PKC炎症反应途径有关,本研究采用超高效液相色谱法测定NE乙酸乙酯部位的药效物质,将SD大鼠随机分为空白组、模型组、羌活组和阳性药组,21天后取关节组织。体外培养的RA-FLS细胞,分为模型组、羌活组和阳性药组。Western blot检测P2X3和PKC炎症途径指标的表达。P2X3抑制剂(A-317491)作用于RA-FLS细胞,并设模型组和阳性药组,检测PKC蛋白的表达。实验发现,NE降低大鼠和RA-FLS细胞中P2X3、Rab7、PKC、NF-κB的蛋白表达。NE和P2X3受体拮抗剂对RA-FLS细胞PKC通路的关键蛋白表达的降低程度相似,且作用没有叠加性。结果表明,NE能够有效改善RA大鼠“上肢痹痛”,其机制与P2X3/Rab7/PKC/NF-κB通路密切相关。

关 键 词：NOTOPTERYGIUM P2X3 receptor Protein kinase c Inflammatory response pathway 

分 类 号：R962[医药卫生—药理学]