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通过一种腺嘌呤衍生物化合物来预防炎症,减少肝纤维化的发展。

Liver fibrotic development is reduced through inflammation prevention by an adenosine derivative compound.

机构信息

Instituto de Fisiología Celular, UNAM, Departamento de Biología Celular y Desarrollo, Laboratorio, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, 04510 México City, Mexico.

Instituto de Fisiología Celular, UNAM, Departamento de Biología Celular y Desarrollo, Laboratorio, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, 04510 México City, Mexico; Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud and The Institute for Obesity Research, Monterrey C.P 64710, Mexico.

出版信息

Biomed Pharmacother. 2023 Sep;165:115216. doi: 10.1016/j.biopha.2023.115216. Epub 2023 Aug 4.

Abstract

BACKGROUND

Liver fibrosis is a global health problem, and studying its development provides important information to address its treatment. Here, we characterized the effects of an adenosine compound (IFC-305) on preventing fibrosis and liver inflammation.

METHODS

We studied the impact of IFC-305 on a carbon tetrachloride-induced liver fibrosis model in Wistar male rats at 4, 6, and 8 weeks. The effects were characterized by liver tissue histology, macrophages identification by flow cytometry with CD163+/CD11b/c+ antibodies, hepatic and plasmatic cytokine levels employing MILLIPLEX MAP and ELISA, Col1a1 and Il6 gene expression by RTqPCR, lipoperoxidation by TBARS reaction, and reactive oxygen species using 2'-7'dichlorofluorescin diacetate.

RESULTS

CCl-induced liver fibrosis and inflammation were significantly reduced in rats treated with IFC-305 at 6 and 8 weeks. In addition, we observed diminished expression of Col1a1; a decrease in the inflammatory cytokines IL-1β, IL-6, MCP-1, TNF-α, and IL-4 a; reduction in inflammatory macrophages; inhibition of lipoperoxidation; and ROS production in Kupffer cells.

CONCLUSION

This study showed that IFC-305 can inhibit liver fibrosis establishment by regulating the immune response during CCl-induced damage. The immunomodulatory action of IFC-305 supports its use as a potential therapeutic strategy for preventing liver fibrosis.

摘要

背景

肝纤维化是一个全球性的健康问题,研究其发展为解决其治疗问题提供了重要信息。在这里,我们描述了一种腺苷化合物(IFC-305)在预防纤维化和肝脏炎症中的作用。

方法

我们研究了 IFC-305 对四氯化碳诱导的 Wistar 雄性大鼠肝纤维化模型在 4、6 和 8 周时的影响。通过肝组织学、流式细胞术检测 CD163+/CD11b/c+抗体鉴定巨噬细胞、MILLIPLEX MAP 和 ELISA 检测肝和血浆细胞因子水平、RTqPCR 检测 Col1a1 和 Il6 基因表达、TBARS 反应检测脂质过氧化、2'-7'-二氯荧光素二乙酸酯检测活性氧来表征作用。

结果

IFC-305 治疗的大鼠在 6 周和 8 周时,CCl 诱导的肝纤维化和炎症明显减轻。此外,我们观察到 Col1a1 表达减少;促炎细胞因子 IL-1β、IL-6、MCP-1、TNF-α和 IL-4α减少;炎症性巨噬细胞减少;脂过氧化抑制;Kupffer 细胞中 ROS 产生减少。

结论

本研究表明,IFC-305 可以通过调节 CCl 诱导损伤过程中的免疫反应来抑制肝纤维化的建立。IFC-305 的免疫调节作用支持其作为预防肝纤维化的潜在治疗策略的使用。

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