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China Pharmacy ; (12): 407-412, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1011319

RESUMO

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis (SF) in rats with knee osteoarthritis (KOA). METHODS Male SD rats were randomly divided into sham operation group, KOA group and Layers adjusting external application group, with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling, the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder (8 g for every 100 cm2), Compound sanhuang ointment (5 g for every 100 cm2)] on the knee joint, 8 h every day, for 28 d in total. After the last administration, the degree of synovitis and fibrosis in rats was observed, and Krenn scoring was performed in each group. The expressions of collagen Ⅰ, high mobility group protein B1 (HMGB1) and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) were detected in the synovial membrane; the contents of interleukin-1β (IL- 1β), IL-6 and tumor necrosis factor-α (TNF-α) in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group, the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement, the inflammatory cell infiltration and collagen fiber deposition were obvious; the positive expressing cells of collagen Ⅰ, HMGB1 and p-NF-κB p65 were increased significantly; the contents of IL-1β, IL-6 and TNF-α in serum, the expressions of fibrosis-related protein (transforming growth factor-β, collagen Ⅰ, tissue inhibitor of metalloproteinase 1, α-smooth muscle actin) and their mRNA as well as theexpressions of HMGB1, TLR4 protein and their mRNA, the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats (P<0.01). Compared with the KOA group, the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved, and the above quantitative indicators were significantly reversed (P<0.05 or P<0.01). CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats, the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

2.
China Pharmacy ; (12): 23-28, 2023.
Artigo em Chinês | WPRIM | ID: wpr-953712

RESUMO

OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription (XBN) on knee osteoarthritis (KOA) model rats based on AMP-activated protein kinase(AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS Totally 36 rats were randomly divided into blank group, model group, XBN group (12.56 g/kg), XBN+metformin (AMPK agonist) group (12.56 g/kg XBN+100 mg/kg metformin), with 9 rats in each group. Except for blank group, KOA model was induced by anterior cruciate ligament transection in other groups. After modeling, each group was given relevant medicine/normal saline, XBN and normal saline intragastrically, once a day, and metformin intraperitoneally, every other day, for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage, mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), ADAMTS-5, matrix metalloproteinase 3 (MMP-3) and MMP- 13, and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group, the structure of cartilage tissue in the model group was disordered, the matrix of cartilage layer was lightly stained,the tide line was distorted or interrupted, and Mankin score was significantly increased (P<0.05). The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly (P<0.05); mRNA and protein expressions of ADAMTS-4, ADAMTS-5, MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues (P<0.05). Compared with model group, the pathological morphology of cartilage was improved significantly in each administration group, and above score or indexes were reversed significantly (P<0.05). Compared with XBN group, the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group, and the levels of above score or indicators were further improved (P<0.05). CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats, promote cartilage synthesis and reduce cartilage degradation, the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.

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