Effect of Guizhi Shaoyao Zhimutang on Cartilage Destruction and JAK2/STAT3 Signaling Pathway in Mice with Collagen-induced Arthritis
10.13422/j.cnki.syfjx.20221403
- VernacularTitle:桂枝芍药知母汤对胶原诱导性关节炎小鼠软骨破坏及JAK2/STAT3信号通路的影响
- Author:
Nan LI
1
;
Haixin YANG
1
;
Shan ZENG
2
;
Qingyu MA
1
;
Jiaxu CHEN
1
Author Information
1. School of Traditional Chinese Medicine,Jinan University,Guangzhou 510632,China
2. The First Affiliated Hospital of Jinan University,Guangzhou 510632,China
- Publication Type:Journal Article
- Keywords:
Guizhi Shaoyao Zhimutang;
rheumatoid arthritis;
cartilage destruction;
collagen-induced arthritis (CIA);
Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(2):52-58
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the effect of Guizhi Shaoyao Zhimutang (GSZMD) on cartilage destruction in mice with collagen-induced arthritis (CIA) and its mechanism. MethodThirty-six DBA/1 mice in SPF grades were randomly divided into 6 groups, namely, the normal group, the model group, the methotrexate (MTX) group, the low-dose GSZMD group, the medium-dose GSZMD group, and the high-dose GSZMD group. Except the normal group, mice in the other 5 groups were used to establish the model of CIA by secondary immunization. The mice were given normal saline, MTX (1.5 mg·kg-1, 2 times a week), and low, medium, and high-doses GSZMD (6.3, 12.6, 25.2 g·kg-1·d-1) by intragastric administration on the day of the onset of hind limb swelling for 4 weeks. The changes in the degree of foot swelling of mice in each group were observed and recorded. The content of matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, and MMP-13 in serum was determined by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the ankle joint were observed by hematoxylin-eosin (HE) staining, and the cartilage destruction was observed by red fast green staining. The protein expression of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in ankle joints were detected by Western blot. ResultAs compared with the normal group, the degree of foot swelling, the content of MMP-1, MMP-3, MMP-9, and MMP-13 in serum and the expression levels of phosphorylation (p)-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints of the model group were increased (P<0.01), and the joint damage was aggravated. As compared with the model group, the degrees of foot swelling of the mice in the MTX group and the low, medium, and high-dose GSZMD group were reduced (P<0.05, P<0.01), and the content of MMP-1, MMP-3, MMP-9, and MMP-13 in serum was decreased (P<0.05, P<0.01). The pathological joint damage was alleviated, and the expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints were decreased in the MTX group and GSZMD groups (P<0.05, P<0.01). ConclusionGSZMD can reduce the degree of joint swelling in mice with CIA, inhibit the expressions of MMP-1, MMP-3, MMP-9, and MMP-13, and alleviate the destruction of articular cartilage. Its mechanism is related to the JAK2/STAT3 signaling pathway.