Xibining Ⅱ attenuates cartilage damage in knee osteoarthritis rats by regulating glycolysis through AMPK/PGC1α signaling pathway
10.3969/j.issn.1000-4718.2025.08.013
- VernacularTitle:膝痹宁Ⅱ通过AMPK/PGC1α信号通路调控糖酵解而减轻膝骨关节炎大鼠软骨损伤
- Author:
Yibao WEI
1
;
Zhenyuan MA
;
Deren LIU
;
Enrui HU
;
Xiaochen LI
;
Peimin WANG
;
Taiyang LIAO
;
Wei MEI
Author Information
1. 南京中医药大学附属医院(江苏省中医院)骨伤科,江苏 南京 210029
- Publication Type:Journal Article
- Keywords:
Xibining Ⅱ;
knee osteoarthritis;
cartilage damage;
glycolysis;
AMPK/PGC1α signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(8):1569-1577
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether Xibining Ⅱ(XBN Ⅱ)attenuates cartilage damage in rats with knee osteoarthritis(KOA)by modulating glycolysis via the AMP-activated protein kinase(AMPK)/peroxisome proliferator-acti-vated receptor γ coactivator 1α(PGC1α)signaling pathway.METHODS:Thirty-two SD rats were randomly divided into sham group,KOA group,XBN Ⅱ group and metformin(AMPK activator)group,with 8 rats in each group.The rats in KOA group were subjected to the anterior cruciate ligament transection procedure to establish the KOA model.Starting from the 14th day after modeling,the rats in XBN Ⅱ group received a daily dose of XBN Ⅱ via gavage once a day,and those in metformin group were administered metformin via intraperitoneal injection once a day for 4 weeks.Subsequently,the histopathological changes of the cartilage were examined by HE and safranin O-fast green staining with matching Mankin and OARSI scores.The protein levels of phosphorylated AMPK(p-AMPK)and PGC1α in cartilage were quanti-fied through immunohistochemistry.In addition,RT-qPCR and Western blot were conducted to measure the mRNA and protein expression levels of glycolysis-related factors,including glucose transporter 1,hexokinase 2 and lactate dehydroge-nase A,biomarkers related to cartilage synthesis and catabolism,such as collagen type Ⅱ,aggrecan,matrix metallopro-teinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5,and AMPK/PGC1α signaling pathway-re-lated indicators.RESULTS:Lactate levels in cartilage and serum were higher in KOA group compared with sham group(P<0.05).Similarly,the cartilage in KOA group exhibited significant surface abrasion and structural damage,with faint-stained matrix and significantly higher Mankin and OARSI scores compared with sham group(P<0.05).Further analysis revealed significant decreases in the mRNA and protein expression levels of factors related to cartilage anabolism and AMPK/PGC1α signaling pathway in KOA group compared with sham group(P<0.05).In contrast,there were marked in-creases in the mRNA and protein expression levels of factors related to cartilage catabolism and glycolysis(P<0.05).No-tably,XBN Ⅱ and metformin treatments significantly improved the cartilage morphology,reduced Mankin and OARSI scores,and reversed the changes in mRNA and protein levels of the aforementioned indexes(P<0.05).CONCLU-SION:Treatment with XBN Ⅱ can alleviate cartilage damage in KOA rats by inhibiting glycolysis,through a mechanism involving activation of the AMPK/PGC1α signaling pathway.
