Khattab Basma Adel, Hammad Maha Osman, Eldken Zienab Helmy, Hellal Doaa, Mohamed Sherin Zohdy, Sakr Noha Hammad
Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Al-Daqhalia Governorate, P.O.No.35516, Mansoura, Egypt.
Mol Med. 2025 May 26;31(1):207. doi: 10.1186/s10020-025-01239-w.
The molecular basis of pancreatic steatosis is not entirely known. Aquaporins (AQPs) are integral membrane proteins involved in a variety of pancreatic functions. Given the little data regarding the potential role of aquaporins in the pathogenesis of pancreatic steatosis, this study was designed to assess the role of aquaporins and the NLRP3-inflammasome in the rat model of high-fat fructose diet (HFFD) and to investigate the impact of vitamin D supplementation and alternate day fasting (ADF) in ameliorating HFFD-induced pancreatic steatosis.
Twenty-four Sprague-Dawley male rats were divided equally into 4 groups. Group I (control group), Group II (HFFD group), Group III (HFFD + ADF group), and Group IV (HFFD + vitamin D group). By the end of the experiment, fasting blood samples were collected for determination of blood glucose, serum insulin, lipid profile, and insulin resistance. Oxidative stress biomarkers (malondialdehyde and reduced glutathione), inflammatory markers (interleukin-1β and TNF-α), and expression of aquaporins (AQP-1, AQP-3, and AQP-7) genes were evaluated in pancreatic tissues. Histopathological examination of the pancreas and immunohistochemistry of the NLRP3-infammasome and AQP-7 were performed.
The HFFD group exhibited pancreatic steatosis with a significant elevation in the levels of blood sugar, serum insulin, insulin resistance, lipid profile, oxidative stress, inflammatory markers, and AQP-3 and AQP-7 mRNA expressions. Regarding histopathology, there were pale vacuolated-stained cytoplasm in acinar pancreatic cells and increased immunoreactivity for AQP-7 and NLRP3-inflammasome. All these parameters improved with ADF and vitamin D supplementation, with more favorable effects for ADF.
ADF and vitamin D treatment ameliorated the effect of the high-fat fructose diet at both levels of the biochemical and histopathological examinations.
胰腺脂肪变性的分子基础尚不完全清楚。水通道蛋白（AQPs）是参与多种胰腺功能的整合膜蛋白。鉴于关于水通道蛋白在胰腺脂肪变性发病机制中潜在作用的数据较少，本研究旨在评估水通道蛋白和NLRP3炎性小体在高脂果糖饮食（HFFD）大鼠模型中的作用，并研究补充维生素D和隔日禁食（ADF）对改善HFFD诱导的胰腺脂肪变性的影响。
将24只雄性Sprague-Dawley大鼠平均分为4组。第一组（对照组），第二组（HFFD组），第三组（HFFD + ADF组）和第四组（HFFD + 维生素D组）。实验结束时，采集空腹血样以测定血糖、血清胰岛素、血脂谱和胰岛素抵抗。评估胰腺组织中的氧化应激生物标志物（丙二醛和还原型谷胱甘肽）、炎症标志物（白细胞介素-1β和肿瘤坏死因子-α）以及水通道蛋白（AQP-1、AQP-3和AQP-7）基因的表达。进行胰腺的组织病理学检查以及NLRP3炎性小体和AQP-7的免疫组织化学检查。
HFFD组出现胰腺脂肪变性，血糖、血清胰岛素、胰岛素抵抗、血脂谱、氧化应激、炎症标志物水平以及AQP-3和AQP-7 mRNA表达显著升高。在组织病理学方面，胰腺腺泡细胞的细胞质出现淡染空泡状染色，AQP-7和NLRP3炎性小体的免疫反应性增加。ADF和补充维生素D后所有这些参数均得到改善，ADF的效果更显著。
在生化和组织病理学检查两个层面上，ADF和维生素D治疗均改善了高脂果糖饮食的影响。
