Effect of Sanguinarine on Cartilage Injury in Osteoarthritis Rats through the SIRT1/AMPK/PGC-1α Signaling Pathway

Author：ZHANG Huawei, WANG Wenge, WU Jianlin, YANG Hui

Unit：Linfen Central Hospital, Linfen Shanxi 041000, China

Quote：引用：张华伟，王文革，吴建临，杨辉.血根碱通过SIRT1/AMPK/PGC-1α信号通路对骨关节炎大鼠软骨损伤影响的研究[J].中医药导报,2026,32(4):13-17.

DOI：10.13862/j.cn43-1446/r.2026.04.003

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Abstract：

Objective: To investigate the effect of sanguinarine (SAG) on cartilage injury in osteoarthritis (OA) rats by regulating the silent information regulator 1 (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferation-activated receptor-γ-coactivator 1α (PGC-1α) signaling pathway. Methods: An OA rat model was constructed using monosodium iodoacetate (MIA), and rats were randomly divided into OA group, low-dose SAG group, high-dose SAG group, and high-dose SAG + SIRT1 inhibitor group, with 12 rats in each group. Additionally, another 12 healthy rats were used as the control group. After 4 weeks of intervention, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the cartilage tissue of rats in each group were measured. Enzyme linked immunosorbent assay (ELISA) was used to detect interleukin-6 (IL-1), CXCL10, and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. HE staining was used to observe the pathological changes of cartilage tissue in each group. TUNEL staining was used to detect cell apoptosis in cartilage tissues of rats in each group. Western blotting was used to detect the expression of SIRT1/AMPK/PGC-1α pathway related proteins in the cartilage tissues of rats in each group. Results: After OA modeling and processing, the SOD activity, and the expression levels of SIRT1, p-AMPK/AMPK, and PGC-1α proteins in the cartilage tissue decreased significantly, while the MDA content, IL-6, CXCL10, TNF-α levels, and the apoptosis rate increased significantly. After intervention with low-dose and high-dose SAG, the SOD activity, and the expression levels of SIRT1, p-AMPK/AMPK, and PGC-1α proteins in the cartilage tissue increased significantly, while the MDA content, IL-6, CXCL10, TNF-αlevels, and the apoptosis rate decreased significantly. Moreover, the high-dose SAG intervention showed a stronger improvement effect on all indicators compared to the low-dose intervention. However, when SAG high-dose intervention was combined with SIRT1 inhibitor treatment, the SOD activity, and the expression levels of SIRT1, p-AMPK/AMPK, and PGC-1α proteins in the cartilage tissue were lower compared to the high-dose SAG treatment alone, while the MDA content, IL-6, CXCL10, TNF-α levels, and the apoptosis rate were higher. Conclusion: SAG may improve cartilage injury in OA rats by activating the SIRT1/AMPK/PGC-1α signaling pathway.

Key words：osteoarthritis; cartilage injury; Sanguinarine; SIRT1/AMPK/PGC-1α pathway; rat

摘要：

目的：探究血根碱（SAG）调节沉默信息调节因子1（SIRT1）/5′-磷酸腺苷激活的蛋白激酶（AMPK）/氧化物酶体增殖物激活受体γ共激活剂-1α（PGC-1α）信号通路对骨关节炎（OA）大鼠软骨损伤的影响。方法：利用碘乙酸钠（MIA）构建OA大鼠模型，随机将大鼠分为OA组、SAG低剂量组、SAG高剂量组、SAG高+SIRT1抑制剂组，每组各12只，另取12只健康大鼠为对照组。干预4周后，检测各组大鼠软骨组织中SOD、MDA水平；ELISA检测各组大鼠血清中IL-6、CXCL10、TNF-α水平；HE染色观察各组大鼠软骨组织的病理变化；TUNEL染色检测各组大鼠软骨组织中细胞凋亡情况；Western blotting检测各组大鼠软骨组织中SIRT1/AMPK/PGC-1α通路相关蛋白表达。结果：在OA建模处理后，软骨组织中SOD活性及SIRT1、p-AMPK/AMPK、PGC-1α蛋白表达水平均显著降低，而MDA含量、IL-6、CXCL10、TNF-α水平及细胞凋亡率均显著升高；经SAG低剂量和高剂量干预后，SOD活性及SIRT1、p-AMPK/AMPK、PGC-1α蛋白表达水平均显著回升，同时MDA含量、IL-6、CXCL10、TNF-α水平及细胞凋亡率均下降，且SAG高剂量干预在各项指标上较低剂量干预表现出更强的改善效应；而在SAG高剂量干预基础上联合SIRT1抑制剂处理后，SOD活性及SIRT1、p-AMPK/AMPK、PGC-1α蛋白表达水平较SAG单独高剂量处理下降，MDA含量、IL-6、CXCL10、TNF-α水平及细胞凋亡率则回升。结论：SAG可能通过能激活SIRT1/AMPK/PGC-1α信号通路改善OA大鼠软骨损伤。

关键词：骨关节炎；软骨损伤；血根碱；SIRT1/AMPK/PGC-1α通路；大鼠

Release time：2026-04-26

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