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5-甲氧基色氨酸通过抑制肠道上皮损伤和炎症反应缓解葡聚糖硫酸钠诱导的结肠炎。

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

机构信息

Department of Rheumatology and Immunology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Rheumatology and Immunology Shanghai Tenth People's Hospital Tongji University School of Medicine, Shanghai, China.

出版信息

Mediators Inflamm. 2024 Jul 17;2024:1484806. doi: 10.1155/2024/1484806. eCollection 2024.

Abstract

BACKGROUND

Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis.

MATERIALS AND METHODS

To verify the anti-inflammatory effect of 5-MTP , we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level.

RESULTS

This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis . Moreover, it inhibits inflammation and M1 polarization response .

CONCLUSION

5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

摘要

背景

结肠炎是一种难治性肠道炎症性疾病,严重影响患者的生活质量,并增加恶化的风险。导致结肠炎的主要因素包括感染、血流不足以及胶原蛋白和白细胞的堆积。在各种可用的治疗方法中,5-甲氧基色氨酸(5-MTP)已成为通过抑制炎症损伤的保护剂之一。然而,目前尚无关于 5-MTP 在结肠炎治疗中的作用的报道。

材料和方法

为了验证 5-MTP 的抗炎作用,我们首先构建了葡聚糖硫酸钠诱导的结肠炎小鼠模型。此外,通过western blot(WB)和苏木精-伊红染色分析检测巨噬细胞浸润和炎症因子的释放。通过 WB 分析、免疫荧光和末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色检测肠上皮细胞紧密连接损伤和细胞凋亡。最后,我们检测了细胞炎症的产生,并分析了 5-MTP 对 M1 极化的影响。

结果

本研究首次证实 5-MTP 对结肠炎具有良好的治疗效果。5-MTP 抑制巨噬细胞浸润和炎症因子的产生。除了对免疫细胞的作用外,5-MTP 还显著抑制肠上皮细胞紧密连接损伤和细胞凋亡。此外,它还抑制炎症和 M1 极化反应。

结论

5-MTP 对抗过度炎症,从而防止肠上皮紧密连接损伤。此外,抑制细胞凋亡表明 5-MTP 可能是结肠炎的潜在治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bca1/11390199/5612dc068ec5/MI2024-1484806.001.jpg

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