中药药理与临床2025,Vol.41Issue(3):9-14,6.
独活寄生汤通过调控外泌体miRNA表达谱改善大鼠骨关节炎的作用机制
Duhuo Jisheng(独活寄生)Decoction Ameliorates Osteoarthritis in Rats by Regulating the Expression Profile of Exosomal miRNAs
摘要
Abstract
Objective:To observe the effect of Duhuo Jisheng(独活寄生)Decoction on the miRNA expression profile in the rat model of osteoar-thritis(OA)and explore the anti-OA mechanism of the decoction.Methods:Twenty-four SD rats were randomly assigned into normal con-trol,model control,and Duhuo Jisheng Decoction(8.37 g/kg)groups.Sodium iodoacetate solution was injected into the knee joint cavity for the modeling of OA in the rats of other groups except the normal control group.After 4 weeks of drug administration by gavage,hematoxylin-eosin and safranin O-fast green staining was employed to observe the pathological changes in the cartilage tissue and synovial tissue of knee joints.ELISA was employed to determine the serum levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.Western blotting was employed to determine the expression levels of collagen II(COL-II)and matrix metalloproteinase-13(MMP-13)in the cartilage tissue.After isolation and identification of serum exosomes,miRNA sequencing was conducted to screen differentially expressed miRNAs,and their target genes were predicted.Results:Compared with the normal control group,the model control group exhibited cartilage damage and synovial in-flammation,with elevated serum levels of IL-1β and TNF-α(P<0.01),down-regulated expression of COL-II(P<0.01),and up-regulated expression of MMP-13(P<0.01).In comparison with the model control group,Duhuo Jisheng Decoction(8.37 g/kg)alleviated cartilage damage and synovial inflammation in the rat model of OA,lowered the serum levels of IL-1β and TNF-α(P<0.01),up-regulated the expres-sion of COL-II(P<0.01),and down-regulated the expression of MMP-13(P<0.05).A total of 6 differentially expressed exosomal miRNAs(effector miRNAs)were screened by sequencing after OA rats were treated by Duhuo Jisheng Decoction.Bioinformatics analysis showed that the effector miRNAs may exert the therapeutic effects via FoxO,MAPK,and mTOR signaling pathways.Conclusion:Duhuo Jisheng Decoction may alleviate cartilage damage and synovial inflammation by regulating the expression profile of exosomal miRNAs in the serum of OA rats,thus exerting its anti-OA effect.关键词
独活寄生汤/骨关节炎/外泌体/微小核糖核酸/Ⅱ型胶原蛋白/金属蛋白酶-13Key words
Duhuo Jisheng(独活寄生)Decoction/Osteoarthritis/Exosome/MicroRNA/COL-II/MMP-13引用本文复制引用
伍搏宇,杨雷,段建辉,杨卓,简功辉,卢国樑,王海彬,熊辉,齐新宇..独活寄生汤通过调控外泌体miRNA表达谱改善大鼠骨关节炎的作用机制[J].中药药理与临床,2025,41(3):9-14,6.基金项目
湖南省教育厅科学研究项目(编号:21A0248、21B0377、23B0343) (编号:21A0248、21B0377、23B0343)
湖南省中医药科研计划项目(编号:2021002、D2022033、C2023031) (编号:2021002、D2022033、C2023031)
湖南省自然科学基金面上项目(编号:2022JJ30087、2024JJ6342) (编号:2022JJ30087、2024JJ6342)
常德市科技局科研创新引导项目(编号:CDKJJ20220357). (编号:CDKJJ20220357)