nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2026, 02, v.50 175-181
羌活-独活药对调节NF-κB信号通路减轻膝骨关节炎大鼠炎症因子表达的作用机制研究
基金项目(Foundation): 贵州中医药大学研究生教育创新计划项目(YCXKYS2023025);贵州中医药大学研究生教育创新计划项目(YCXKYS2023003)
邮箱(Email): xyk_2005@163.com;
DOI:
摘要:

目的 研究羌活-独活药对(QDHP)调节NF-κB信号通路缓解木瓜蛋白酶诱导的膝骨关节炎(KOA)大鼠膝关节炎症的作用与机制。方法 将25只SPF级SD大鼠随机分组,分为正常组、模型组和给药组(低剂量组QDHP浸膏剂量为2.1 mg/kg,中剂量组为4.2 mg/kg,高剂量组为8.4 mg/kg),5只/组。除正常组外均于第1、4、7天采用4%木瓜蛋白酶溶液与L-同型半胱氨酸混合液诱导造模,末次注射后驱赶14 d,每天15 min;第15天开始给药,2天1次,连续20天。采用游标卡尺记录治疗前后大鼠患侧膝关节横向直径,采用改良奎森行为学评分(Lequesne MG)评估各组实验大鼠行为学变化。取材收集大鼠血清和膝关节,使用番红O-固绿、HE染色分别检测各组大鼠软骨与滑膜组织病理形态,使用ELISA法检测各组大鼠血清促炎因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,使用Western Blot法检测大鼠关节软骨与滑膜组织NF-κB通路p-IκBα、IκBα及p-p65、p65相关蛋白表达。结果 与模型组比较,给药后除QDHP低剂量组外,QDHP中、高剂量组关节肿胀程度、关节炎指数均显著降低(P<0.05),QDHP各给药组大鼠血清及关节液中TNF-α、IL-1β水平均显著降低,p-IκBα/IκBα、p-p65/p65均明显降低(P<0.01)。结论 QDHP可以改善KOA大鼠关节疼痛、肿胀等症状,作用机制可能与抑制NF-κB信号通路激活进而降低炎症因子水平有关。

Abstract:

Objective To investigate the role and mechanism of Qianghuo-Duhuo Herb Pair(QDHP) in modulating the NF-κB signaling pathway to alleviate papain-induced inflammation in the knee osteoarthritis(KOA) rats. Methods 25 SPF-grade SD rats were randomly grouped into normal, model, QDHP-treated groups(low-dose group: extract dose of 2.1 mg/kg; medium-dose group: extract dose of 4.2 mg/kg; high-dose group: extract dose of 8.4 mg/kg), 5 rats per group. Modeling was induced by 4% papain solution mixed with L-homocysteine on days 1, 4, and 7, except for the normal group, which was allowed to move for 14 days after the last injection for 15 min daily. Dosing started on day 15, once every 2 days for 20 days. Vernier calipers were used to record the transverse diameters of the affected knee joints before and after treatment, and the behavioral changes of rats in each group were assessed by the modified Lequesne MG behavioral score. The serum and knee joints of rats were collected, and the histopathological morphology of cartilage and synovial membrane of rats in each group was examined by safranin O-fast green staining and HE staining; the levels of pro-inflammatory factors IL-1β and TNF-α in serum of rats in each group were examined by ELISA; and the expression of the NF-κB pathways p-IκBα, IκBα, p-p65, and p65-associated protein was examined by western blot in the cartilage and synovium of rats in each group. protein expression. Results Compared with the model group, the degree of joint swelling and arthritis index were significantly reduced in the QDHP middle and high dose groups except the QDHP low dose group(P<0.05), and the levels of TNF-α and IL-1β in the serum and joint fluids of the rats in each QDHP-treated group were significantly reduced, and the levels of p-IκBα/IκBα and p-p65/p65 were significantly reduced(P<0.01). Conclusion QDHP can improve the symptoms of joint pain and relieve swelling in KOA rats, and the mechanism of action may be related to the inhibition of NF-κB signaling pathway activation, thereby reducing the levels of inflammatory factors.

参考文献

[1] 王欢.中西医结合治疗膝骨关节炎(膝痹)专家共识[J].世界中医药,2023,18(17):2407-2412.

[2] Lv Z,Yang Y X,Li J,et al.Molecular classification of knee osteoarthritis[J].Front Cell Dev Biol,2021,9:725568.

[3] 崔龙慷,李学飞,沈高波,等.强骨饮联合西药治疗肾虚血瘀型膝骨关节炎合并骨质疏松症临床疗效观察[J].中华中医药杂志,2022,37(9):5512-5516.

[4] 杨永菊,任艳玲,郑曲,等.右归丸治疗膝骨性关节炎作用机制的研究进展[J].中华中医药学刊,2022,40(7):59-62.

[5] Zhang L,Li M,Li X,et al.Characteristics of sensory innervation in synovium of rats within different knee osteoarthritis models and the correlation between synovial fibrosis and hyperalgesia[J].J Adv Res,2021,35:141-151.

[6] 国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2020:275-276.

[7] 梁霄,李娅兰,张筠昊,等.基于TLR2/p38 MAPK/NF-κB信号通路探讨独活寄生汤对类风湿性关节炎大鼠的抗炎作用及机制[J].中国实验方剂学杂志,2023,29(11):43-52.

[8] 倪杰.羌活醇、黄芩素、当归多糖对LPS诱导RAW264.7细胞极化的影响[D].南京:南京中医药大学,2022.

[9] 张晓萍,白莉,冯思凡,等.基于数据挖掘的中药治疗类风湿性关节炎用药规律分析[J].中药药理与临床,2024,40(5):92-96.

[10] 丁芳芳,田丙坤.基于中医传承辅助平台探讨金元四大家治疗头痛的用药规律[J].广东药科大学学报,2023,39(2):139-144.

[11] 张茂,张文欣,宋安东,等.基于TLR4/NF-κB信号通路运用针灸治疗膝骨关节炎的进展[J].宁夏医学杂志,2024,46(7):637-640.

[12] Guan T,Ding L G,Lu B Y,et al.Combined administration of curcumin and chondroitin sulfate alleviates cartilage injury and inflammation via NF-κB pathway in knee osteoarthritis rats[J].Front Pharmacol,2022,13:882304.

[13] 陈奇.中药药理研究方法学[M].3版.北京:人民卫生出版社,2011:140-145.

[14] 蔡美玲.健康教育联合运动方案对KOA手法治疗后患者的随访研究[D].北京:北京中医药大学,2022.

[15] 吴鹏,时孝晴,廖太阳,等.羌活—独活治疗膝骨关节炎的作用机制[J].中国骨质疏松杂志,2022,28(2):262-268.

[16] 胡晓慧,胡蕖,陈兴华,等.雷火灸联合中药外敷治疗神经根型颈椎病28例[J].中国针灸,2019,39(12):1308-1310.

[17] 许霞,孙广瀚,李笑男,等.新安医籍中含药对“羌活—独活”治疗痹病方剂的探析[J].湖北民族大学学报(医学版),2022,39(3):39-43.

[18] 胡晓慧,胡蕖,陈兴华,等.雷火灸联合中药外敷治疗神经根型颈椎病28例[J].中国针灸,2019,39(12):1308-1310.

[19] 许霞,孙广瀚,李笑男,等.新安医籍中含药对“羌活—独活”治疗痹病方剂的探析[J].湖北民族大学学报(医学版),2022,39(3):39-43.

[20] 黑晓晶,吕耀中,李良,等.基于NLRP3/ASC/Caspase-1信号通路探讨独活醇提物对MSU诱导的痛风性关节炎的治疗作用[J].中国实验方剂学杂志,2023,29(13):79-87.

[21] 马丽梅,杨军丽.羌活药材的化学成分和药理活性研究进展[J].中草药,2021,52(19):6111-6120.

[22] 陈颖,杨飞燕,周喆,等.高效液相色谱法同时测定独活中8种香豆素类化合物的含量[J].中药新药与临床药理,2022,33(3):380-385.

[23] 段凯旋,李跃文,刘和波,等.基于网络药理学的羌活—独活药对抗炎作用机制研究[J].中国药房,2019,30(9):1241-1246.

[24] 何广铭,卢晓莹,夏天睿,等.UPLC指纹图谱结合化学计量学分析和多指标成分含量测定的羌活药材质量评价研究[J].中国中医药信息杂志,2024,31(8):126-132.

[25] 祁庆瑞,翟秉涛,岳宝森,等.羌活胜湿汤物质基准量值传递分析[J].中国药学杂志,2024,59(2):128-135.

[26] 杨爽,孙雨婷,张有为,等.基于网络药理学研究羌活—菊花药对治疗冠心病的作用机制[J].中国当代医药,2023,30(10):12-17,197.

[27] 汤露环,吴梦茹,陈妍妍,等.羌活抗类风湿性关节炎活性成分及作用机制的研究进展[J].中草药,2024,55(9):3137-3145.

[28] Tang Z,Zheng R,Chen P,et al.Phytochemistry and biological profile of the chinese endemic herb genus notopterygium[J].Molecules,2024,29(14):3252.

[29] 孙瑞,杨宇,赵彦宇,等.独活寄生汤治疗痹症研究进展[J].陕西中医,2024,45(3):420-423.

[30] 祁庆瑞,翟秉涛,岳宝森,等.羌活胜湿汤物质基准量值传递分析[J].中国药学杂志,2024,59(2):128-135.

[31] 吴厅.类风湿Ⅰ号对佐剂型关节炎大鼠血清TNF-α、IL-6及骨组织DKK1、β-catenin影响的研究[D].杭州:浙江中医药大学,2019.

[32] Liu J,Liu S,Pan W,et al.Wogonoside attenuates the articular cartilage injury and the infiltration of Th1/Th2-type cytokines in papain-induced osteoarthritis in rat model via inhibiting the NF-κB and ERK1/2 activation[J].Immunopharmacol Immunotoxicol,2021,43(3):343-352.

[33] Xu J,Sun Q,Qiu M,et al.Exploring the pharmacological mechanism of Glycyrrhiza uralensis against KOA through integrating network pharmacology and experimental assessment[J].J Cell Mol Med,2024,28(9):e18319.

[34] 张小琴,李情,薛平聚,等.不同刺灸法对膝关节骨关节炎大鼠关节软骨形态结构及NF-κB p65/NLRP3通路的影响[J].针刺研究,2023,48(2):185-191.

基本信息:

中图分类号:R285.5

引用信息:

[1]杨二坤,杜典河,谢斌,等.羌活-独活药对调节NF-κB信号通路减轻膝骨关节炎大鼠炎症因子表达的作用机制研究[J].贵州医药,2026,50(02):175-181.

基金信息:

贵州中医药大学研究生教育创新计划项目(YCXKYS2023025);贵州中医药大学研究生教育创新计划项目(YCXKYS2023003)

发布时间:

2026-02-27

出版时间:

2026-02-27

检 索 高级检索