Saracatinib是一种Src激酶抑制剂，可增强二甲双胍和氯沙坦对糖尿病肾病的肾保护作用。

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2025-01-07 DOI:10.1080/13813455.2024.2449404

Suzan A Khodir, Eman M Sweed, Mona A Kora, Nader G Zaki, Ghada S Amer, Omnia Ameen

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引用次数: 0

摘要

目的：本研究评估saracatinib （Src）在糖尿病肾病（DN）中的肾保护作用及其潜在的潜在过程。材料与方法：将大鼠分为：对照组、DN、DN + Met + Los、DN + Met + Src和DN + Met + Los + Src。测定大鼠ABP、尿白蛋白、尿肾素和肌酐清除率。采集血样，测定血糖状态参数、肾功能、氧化应激标志物、炎症介质、醛固酮和血脂。取肾进行KIM-1和nephrin基因表达、H&E、Masson三色染色和免疫组化评估。结果：ABP、尿白蛋白、尿肾素、血糖、尿素、肌酐、醛固酮、炎症因子、MDA、脂质、肾纤维化、VEGF、TGF-β H评分、肾脏KIM-1表达均与DN相关。然而，与对照组相比，DN组肌酐清除率、GSH和nephrin表达明显降低。讨论与结论：二甲双胍（Met）、氯沙坦（Los）和Src联合治疗可修复DN改变。将Src添加到Met和Los中要优于单独使用它们。

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Saracatinib, a Src kinase inhibitor, enhances the renoprotective effect of metformin and losartan in diabetic nephropathy.

Objective: This research assesses renoprotective effects of saracatinib (Src) in diabetic nephropathy (DN) and the potential underlying processes.

Materials and methods: Rats were divided into: control, DN, DN + Met + Los, DN + Met + Src, and DN + Met + Los + Src. Rats' ABP, urinary albumin, urinary nephrin, and creatinine clearance were assessed. Blood samples were collected for measuring glycaemic state parameters, renal functions, oxidative stress markers, inflammatory mediators, aldosterone, and lipid profile. Kidneys were extracted for KIM-1 and nephrin gene expression, H&E, Masson's trichrome staining, and immunohistochemical assessment.

Results: Significant increases in ABP, urinary albumin and nephrin, glycaemic measurements, urea, creatinine, aldosterone, inflammatory cytokines, MDA, lipids, renal fibrosis, H scores of VEGF and TGF-β, and renal KIM-1 expression were related to DN. However, there was a significant decrease in creatinine clearance, GSH, and nephrin expression in DN group compared with control group.

Discussion and conclusion: The combination of metformin (Met), losartan (Los), and Src repaired DN alterations. Adding Src to Met and Los is superior to using them alone.

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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.