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黄连素在痛风性关节炎大鼠模型中的抗关节炎活性

Antiarthritic activities of berberine in a rat model of gouty arthritis.

作者信息

Ibrahim Fouad Ghadha, Aly Hanan F, Shalaby Mohamed B, Mabrouk Mohamed I, Khalil Wagdy K B, Rizk Maha Z

机构信息

Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.

Department of Toxicology Research, Research Institute of Medical Entomology (RIME), General Organization of Teaching Hospitals and Institutes (GOTHI), Ministry of Health and Population (MoHP), Dokki, Cairo, 12311, Egypt.

出版信息

Sci Rep. 2025 Sep 1;15(1):32153. doi: 10.1038/s41598-025-16622-0.

Abstract

Gouty arthritis (GA) is an inflammatory arthritic disorder that is characterized by intense, acute inflammatory responses, such as synovitis and arthritis that occur due to articular deposition of monosodium urate (MSU) crystals. This study has compared the therapeutic potentials of either Berberine (BERB) or Paracetamol (Para) on MSU-induced inflammation in rat model of Gouty arthritis (GA). GA was induced by "intra-articular" injection of MSU suspension (20 mg/ml) inside the knee joint of the rat's right limb. Circumference was measured at 48 h after MSU injection and 14 days post-treatment with BERB or Para. Gait assessment was conducted. Histopathological alterations of knee and paw (ankle) joint tissue were investigated. Serum levels of Malondialdehyde (MDA), monocyte chemotactic protein 1 (MCP-1), Vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) were estimated. Molecular analysis of Elastase, Cyclooxygenase-2 (COX-2), Matrix metalloproteinase-9 (MMP-9), and Myeloperoxidase (MPO) was evaluated. In addition, DNA fragmentation assay was performed. Our results revealed that deposition of MSU crystals in the articular joints provoked an inflammatory response, oxidative stress, and DNA fragmentation (apoptosis). However, the oral treatment of MSU-induced rats with either BERB (50 mg/kg/day) or Para (50 mg/kg/day) for 14 days mitigated MSU-stimulated inflammation and arthritis as represented by the behavioral, histopathological, biochemical, and molecular levels. Treatment of MSU-induced arthritic rats with BERB or Para attenuated oedema and alleviated histological signs of acute inflammation. In addition, treatment decreased chemokine levels and reduced MDA levels. These results indicated that BERB and Para exerted strong anti-inflammatory, anti-oxidative, and anti-apoptotic activities against GA.

摘要

痛风性关节炎(GA)是一种炎性关节疾病,其特征为强烈的急性炎症反应,如因尿酸单钠(MSU)晶体在关节沉积而引发的滑膜炎和关节炎。本研究比较了小檗碱(BERB)和对乙酰氨基酚(Para)对痛风性关节炎(GA)大鼠模型中MSU诱导炎症的治疗潜力。通过在大鼠右肢膝关节“关节内”注射MSU悬液(20mg/ml)诱导GA。在注射MSU后48小时以及用BERB或Para治疗14天后测量周长。进行步态评估。研究膝关节和爪(踝关节)关节组织的组织病理学改变。估计血清丙二醛(MDA)、单核细胞趋化蛋白1(MCP-1)、血管内皮生长因子(VEGF)和前列腺素E2(PGE2)水平。评估弹性蛋白酶、环氧化酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)和髓过氧化物酶(MPO)的分子分析。此外,进行DNA片段化分析。我们的结果显示,MSU晶体在关节中的沉积引发了炎症反应、氧化应激和DNA片段化(凋亡)。然而,用BERB(50mg/kg/天)或Para(50mg/kg/天)对MSU诱导的大鼠进行14天的口服治疗,在行为、组织病理学、生化和分子水平上减轻了MSU刺激的炎症和关节炎。用BERB或Para治疗MSU诱导的关节炎大鼠可减轻水肿并减轻急性炎症的组织学迹象。此外,治疗降低了趋化因子水平并降低了MDA水平。这些结果表明,BERB和Para对GA具有强大的抗炎、抗氧化和抗凋亡活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb63/12402284/da9d1ff43c86/41598_2025_16622_Fig1_HTML.jpg

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