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热量和时间限制喂养改善链脲佐菌素诱导的1型糖尿病大鼠的肝脏和肾脏组织病理学。

Calorie and time-restricted feeding improves liver and kidney histopathology in streptozotocin-induced type 1 diabetic rats.

作者信息

Taufani Indra Putra, Laila Sri Rahmatul, Tasminatun Sri, Simaremare Sailent Rizki Sari, Mardiana Meity, Situmorang Jiro Hasegawa

机构信息

Department of Pharmacist Profession Education, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia.

Division of Anatomy, Histology, and Embryology, School of Veterinary Medicine and Biomedical Science, IPB University, Bogor, Indonesia.

出版信息

Front Physiol. 2025 Aug 21;16:1629751. doi: 10.3389/fphys.2025.1629751. eCollection 2025.

Abstract

Type 1 diabetes (T1D) is associated with severe metabolic dysregulation and organ complications such as hepatomegaly and nephropathy. While insulin therapy remains the cornerstone of treatment, there is growing interest in dietary interventions that modulate metabolic outcomes independently of insulin. This study aimed to investigate the effects of calorie restriction (CR) combined with time-restricted feeding (TRF) on metabolic and histological parameters in a high-fat diet-fed, streptozotocin-induced rat model of T1D. Male Sprague-Dawley rats were divided into control, diabetic, and two CR-TRF groups (day-fed and night-fed). CR-TRF groups received 70% of the diabetic group's caloric intake during either the light or dark phase. Body weight, fasting glucose, oral glucose tolerance test (OGTT), triglycerides, water intake, and calorie intake were measured. Liver and kidney tissues were evaluated using H&E and Cason's Trichrome staining. Although CR-TRF did not significantly improve body weight, both interventions markedly reduced water intake and improved hepatomegaly. OGTT results showed improved slight glycemic responses in CR-TRF groups, particularly in the day-fed group. Diabetic rats exhibited liver and renal damage, which were significantly attenuated by CR-TRF. Histological analysis revealed preserved tissue architecture and reduced vacuolation in both liver and kidney under CR-TRF conditions. These findings support the potential of calorie restriction, regardless of feeding time as adjunct therapies for T1D and warrant further exploration in translational models.

摘要

1型糖尿病(T1D)与严重的代谢失调及器官并发症相关,如肝肿大和肾病。虽然胰岛素治疗仍然是治疗的基石,但人们对独立于胰岛素调节代谢结果的饮食干预的兴趣日益浓厚。本研究旨在探讨热量限制(CR)联合限时进食(TRF)对高脂饮食喂养、链脲佐菌素诱导的T1D大鼠模型的代谢和组织学参数的影响。雄性Sprague-Dawley大鼠分为对照组、糖尿病组和两个CR-TRF组(白天进食组和夜间进食组)。CR-TRF组在光照或黑暗阶段接受糖尿病组热量摄入的70%。测量体重、空腹血糖、口服葡萄糖耐量试验(OGTT)、甘油三酯、水摄入量和热量摄入量。使用苏木精-伊红(H&E)染色和卡森三色染色评估肝脏和肾脏组织。虽然CR-TRF没有显著改善体重,但两种干预措施均显著降低了水摄入量并改善了肝肿大。OGTT结果显示CR-TRF组的轻微血糖反应有所改善,尤其是白天进食组。糖尿病大鼠表现出肝脏和肾脏损伤,CR-TRF显著减轻了这些损伤。组织学分析显示,在CR-TRF条件下,肝脏和肾脏的组织结构得以保留,空泡化减少。这些发现支持了热量限制作为T1D辅助治疗方法的潜力,无论进食时间如何,都值得在转化模型中进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/12408565/267d97df5a6a/fphys-16-1629751-g001.jpg

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