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白杨素和骨髓间充质干细胞通过减轻炎症和氧化应激抑制弗氏完全佐剂诱导的Wistar大鼠关节炎。

Chrysin and Bone Marrow-derived Mesenchymal Stem Cells Restrain Complete Freund's Adjuvant-induced Arthritis in Wistar Rats via Subsiding Inflammation and Oxidative Stress.

作者信息

Mohamed Nermin A, Mazher Khalid M, Sayed Hesham M, Abdelaziz Mohamed A, Samhan Mohamed A, Abdel Rahman Fatma El-Zahraa S, Mahdi Emad A, Halfaya Fatma Mohamed, Ahmed Osama M

机构信息

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, 62521, Egypt.

Histology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.

出版信息

Curr Stem Cell Res Ther. 2025 Jul 15. doi: 10.2174/011574888X367150250701071144.

DOI:10.2174/011574888X367150250701071144
PMID:40671228
Abstract

INTRODUCTION

Rheumatoid arthritis (RA) is an inflammatory disease that causes significant disability and persistent inflammation. Currently, there are no appropriate treatments for RA other than systemic immunosuppressants, which have a variety of undesirable effects after long-term use. Thus, this study aims to determine the anti-arthritis effect of chrysin (5,7-dihydroxyflavone) and/or bone marrow-derived mesenchymal stem cells (BM-MSCs), separately and combined, on CFA (complete Freund's adjuvant)-induced arthritis in rats as an animal model of RA.

METHODS

Male Wistar rats were injected with 100 μL of CFA/rat/day in the paw of the right hind limb for two consecutive days to induce RA. Arthritic rats received chrysin in an oral dose of 100 mg/kg bw each day, BM-MSCs at 1 × 106 cells/rat once per week in complete culture medium into the lateral tail vein, and a combination for 21 days.

RESULTS

The oral administration of chrysin and intravenous injection of BM-MSCs significantly reduced the increased anteroposterior thickness, volume, and circumference of the right hind paw, as well as serum levels of RF, IL-1β, TNF-α, and IL-17, as well as serum MDA level, besides augmenting serum levels of GPx, GST, GSH, and SOD. The arthritic rats treated with chrysin and/or BMMSCs exhibited a significant improvement in the elevated expression levels of IκBα, NF-κB p50, and NF-κB p65 proteins in ankle joint articular tissue. Similarly, the histopathological score and histological sections provided additional evidence of the improvement in arthritic lesions.

DISCUSSION

The treatment with chrysin and BM-MSCs has potential anti-arthritic effects, which may be attributed to their abilities to suppress the inflammation and oxidative stress and enhance the antioxidant defense system. The combinatory effect of chrysin and BM-MSCs was found to be the most effective. However, further clinical studies are required to assess their safety and efficacy in patients with arthritis.

CONCLUSION

Due to their strong antioxidant and anti-inflammatory properties, the combined administration of chrysin and BM-MSCs was found to be more effective in treating arthritis than either treatment alone in Wistar rats.

摘要

引言

类风湿性关节炎(RA)是一种炎症性疾病,会导致严重残疾和持续性炎症。目前,除了全身免疫抑制剂外,尚无针对RA的合适治疗方法,而长期使用这些免疫抑制剂会产生各种不良影响。因此,本研究旨在确定白杨素(5,7-二羟基黄酮)和/或骨髓间充质干细胞(BM-MSCs)单独及联合使用对CFA(完全弗氏佐剂)诱导的大鼠关节炎(作为RA的动物模型)的抗关节炎作用。

方法

雄性Wistar大鼠连续两天在右后肢爪部注射100μL/只/天的CFA以诱导RA。患关节炎的大鼠每天口服100mg/kg体重的白杨素,每周一次将1×10⁶个细胞/只的BM-MSCs在完全培养基中经侧尾静脉注射,联合治疗21天。

结果

口服白杨素和静脉注射BM-MSCs显著降低了右后爪增加的前后厚度、体积和周长,以及血清中RF、IL-1β、TNF-α和IL-17水平以及血清MDA水平,同时提高了血清中GPx、GST、GSH和SOD水平。用白杨素和/或BM-MSCs治疗的患关节炎大鼠踝关节关节组织中IκBα、NF-κB p50和NF-κB p65蛋白的表达水平显著改善。同样,组织病理学评分和组织学切片为关节炎病变的改善提供了额外证据。

讨论

白杨素和BM-MSCs治疗具有潜在的抗关节炎作用,这可能归因于它们抑制炎症和氧化应激以及增强抗氧化防御系统的能力。发现白杨素和BM-MSCs的联合作用最有效。然而,需要进一步的临床研究来评估它们在关节炎患者中的安全性和有效性。

结论

由于其强大的抗氧化和抗炎特性,发现白杨素和BM-MSCs联合给药在治疗Wistar大鼠关节炎方面比单独使用任何一种治疗方法更有效。

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