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用硫氢化钠对骨髓间充质干细胞进行预处理可增强其在II型胶原诱导的关节炎大鼠模型中的治疗潜力。

Preconditioning of bone marrow mesenchymal stem cells with sodium hydrosulfide enhances their therapeutic potential in type II collagen-induced arthritis rat model.

作者信息

El-Sayed Sara M, Ahmed Hanaa H, Aglan Hadeer A, Naguib Mohamed M, Mohamed Mohamed R

机构信息

Biochemistry Department, Faculty of Science, Ain Shams University, P.O. 11566, Cairo, Egypt.

Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 May 14. doi: 10.1007/s00210-025-04222-8.

DOI:10.1007/s00210-025-04222-8
PMID:40366399
Abstract

This study was conducted to evaluate the impact of sodium hydrogen sulfide (NaHS) on the therapeutic efficacy of bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of collagen-induced arthritis (CIA) rats. MSCs were isolated and cultured from rat bone marrow, and their characteristics were determined. The CIA model was induced in rats by intradermal injections of type II collagen on days 0 and 21. A variety of treatments were administered, including naproxen, BM-MSCs, BM-MSC-conditioned media, NaHS, BM-MSCs preconditioned with NaHS, and BM-MSCs preconditioned with NaHS-conditioned media. The infused BM-MSCs homed to the bone trabeculae and cartilage of the knee joint, leading to significant improvements in gait scores and a reduction in paw withdrawal frequency (PWF). Treatment with BM-MSCs and NaHS also significantly suppressed serum levels of CRP, RF, and 14-3-3η, while downregulating TNF-α gene expression and MMP-1 protein levels in the synovial membrane. Histopathological analysis confirmed these biochemical and molecular genetic findings. Notably, CIA rats treated with BM-MSCs preconditioned with NaHS showed the most significant improvements, with outcomes closely resembling those of healthy controls. This study concludes that NaHS enhances the therapeutic efficacy of BM-MSC therapy for rheumatoid arthritis (RA) by augmenting their anti-inflammatory, immunomodulatory, and regenerative properties.

摘要

本研究旨在评估硫化氢钠(NaHS)对骨髓间充质干细胞(BM-MSCs)治疗胶原诱导性关节炎(CIA)大鼠疗效的影响。从大鼠骨髓中分离并培养MSCs,并对其特性进行测定。在第0天和第21天通过皮内注射II型胶原诱导大鼠建立CIA模型。给予多种治疗,包括萘普生、BM-MSCs、BM-MSC条件培养基、NaHS、用NaHS预处理的BM-MSCs以及用NaHS条件培养基预处理的BM-MSCs。注入的BM-MSCs归巢至膝关节的骨小梁和软骨,导致步态评分显著改善, paw withdrawal frequency(PWF)降低。BM-MSCs和NaHS治疗还显著抑制了血清中CRP、RF和14-3-3η的水平,同时下调了滑膜中TNF-α基因表达和MMP-1蛋白水平。组织病理学分析证实了这些生化和分子遗传学结果。值得注意的是,用NaHS预处理的BM-MSCs治疗的CIA大鼠显示出最显著的改善,其结果与健康对照组非常相似。本研究得出结论,NaHS通过增强BM-MSCs的抗炎、免疫调节和再生特性,提高了其对类风湿性关节炎(RA)的治疗效果。

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Fundam Clin Pharmacol. 2025 Feb;39(1):e13050. doi: 10.1111/fcp.13050.
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Pyrazole derivatives ameliorate synovial inflammation in collagen-induced arthritis mice model via targeting p38 MAPK and COX-2.
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Cell J. 2023 Dec 31;25(12):854-862. doi: 10.22074/cellj.2023.2004504.1326.
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