沙格列扎抑制高脂饮食和低剂量链脲佐菌素诱导的 Wistar 大鼠糖尿病肾病中的 KIM-1 和 IV 型胶原蛋白。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/ijbms.2024.78221.16908
Rizwan Ahamad, Uma Bhandari, Sayima Nabi, Shweta Sharma
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引用次数: 0

摘要

目的:肾病是与 T2D 相关的最常见合并症。本研究旨在探讨高脂饮食和低剂量链脲佐菌素诱导的 Wistar 大鼠糖尿病肾病中 saroglitazar 的潜力:以沙格列扎尔和非诺贝特为研究对象,对IV型胶原蛋白和肾损伤分子-1(KIM-1)的配体结合区进行了分子对接模拟研究。研究人员给大鼠喂食常规啮齿类动物食物或高脂肪食物,为期两周。两周后,给予高脂饮食的大鼠低剂量 STZ(35 毫克/千克,IP)。实验诱导的糖尿病大鼠分为五组:正常对照组;糖尿病对照组;HFD+STZ+沙格列扎尔(2 毫克/千克)组;HFD+STZ+沙格列扎尔(4 毫克/千克)组;HFD+STZ+非诺贝特(100 毫克/千克)组。21 天后,大鼠禁食一夜,采集血液和尿液进行各种生化分析。动物被处死后,取出肾脏组织进行组织病理学研究:硅学研究表明,沙格列扎尔和非诺贝特与 KIM-1 和 IV 型胶原蛋白有很强的亲和力。结论:沙格列扎尔对肾功能有明显的抑制作用:Saroglitazar 通过改善肾功能减轻了 HFD+STZ 诱导的 Wistar 大鼠 DN 的肾损伤。
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Saroglitazar suppresses KIM-1 and type IV collagen in high fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.

Objectives: Nephropathy is the most common comorbidity linked to T2D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.

Materials and methods: Molecular docking simulation investigations were conducted on the ligand-binding region of type IV collagen and Kidney injury molecule-1 (KIM-1), using saroglitazar and fenofibrate as the subjects. The rats were fed either a conventional rodent diet or a high-fat diet ad libitum for two weeks. Following a two-week period, the rats given an HFD were administered with a low-dose of STZ (35 mg/kg, IP). Rats with experimentally induced diabetes were categorized into five groups: normal control; diabetic control; HFD+STZ+saroglitazar (2 mg/kg); HFD+STZ+saroglitazar (4 mg/kg); HFD+STZ+fenofibrate (100 mg/kg) treated orally for 21 days with continuation on HFD. After 21 days, rats were kept on fasting overnight, blood and urine was acquired for various biochemical analysis. Animals were sacrificed, and kidney tissues were removed for histopathological studies.

Results: In-silico investigation showed a substantial affinity between saroglitazar and fenofibrate with KIM-1 and type IV collagen. Saroglitazar produced a significant (P<0.01) reduction in weight of the body, serum blood sugar, albumin, creatinine, and BUN levels. Further, saroglitazar significantly (P<0.01) reduced the KIM-1 and type IV collagen levels in the urine of diabetic rats. Histopathological results showed improvement in tubular degeneration, necrosis, and dilatation of Bowman's space in kidney tissue.

Conclusion: Saroglitazar attenuated renal injury by improving renal function in HFD+STZ-induced DN in Wistar rats.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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