二表肽酶-4（DPP-4）抑制剂可在糖尿病大鼠非酒精性脂肪肝模型中下调 HMGB1/TLR4/NF-κB 信号通路。

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-02-01 Epub Date: 2021-09-20 DOI:10.1080/13813455.2021.1975758

Mona M Allam, Reham M Ibrahim, Walaa Bayoumie El Gazzar, Mona A Said

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引用次数: 0

摘要

背景：炎症和免疫途径在非酒精性脂肪肝（NAFLD）的病理生理学中起着至关重要的作用。西他列汀可阻断二肽基肽酶-4（DPP-4）酶，但改变炎症通路和先天性免疫系统的机制以及西他列汀通过何种途径影响非酒精性脂肪肝的发病机制尚未得到讨论：本研究旨在了解西他列汀与先天性免疫反应之间的相互作用，以改善非酒精性脂肪肝：方法：将32只雄性白化Wistar大鼠分为四组。方法：32 只雄性 Wistar 白化大鼠分为四组，每组接受标准饮食或高脂饮食（添加或不添加西格列汀）。对血清 HMGB1、肝脏 TLR4 和 NF-κB 蛋白和 mRNA 表达、炎症细胞因子以及组织病理学变化进行了分析：结果：西他列汀通过减少HMGB1介导的TLR4/NF-κB信号传导，抑制炎症反应，减轻胰岛素抵抗，从而改善非酒精性脂肪肝：结论：西他列汀实际上可能被证明是一种有益于非酒精性脂肪肝的治疗干预措施。

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Dipeptedyl peptidase-4 (DPP-4) inhibitor downregulates HMGB1/TLR4/NF-κB signaling pathway in a diabetic rat model of non-alcoholic fatty liver disease.

Context: Inflammatory and immune pathways play a crucial role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Sitagliptin blocks the dipeptidyl peptidase-4 (DPP-4) enzyme, mechanisms that alter inflammatory pathways and the innate immune system, and by which Sitagliptin affects the pathogenesis of NAFLD weren't previously discussed.

Objective: This study aims to understand the interaction between Sitagliptin and innate immune response in order to meliorate NAFLD.

Methods: Thirty- two Wistar male albino rats were categorised into four groups. Rats have received a standard diet or a high-fat diet either with or without Sitagliptin. Serum HMGB1, protein and mRNA expressions of hepatic TLR4 and NF-κB, inflammatory cytokines, and histopathological changes were analysed.

Results: An ameliorative action of Sitagliptin in NAFLD was demonstrated via decreasing HMGB1-mediated TLR4/NF-κB signalling in order to suppress inflammation and reduce insulin resistance.

Conclusion: Sitagliptin may in fact prove to be a beneficial therapeutic intervention in NAFLD.

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来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.