Erol Zeki, Rugji Jerina, Aydoğan Ayşe, Özmen Özlem, Taşçı Fulya
Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Dokuz Eylül University, Kiraz, İzmir, Turkey.
Department of Food Science, University of Wisconsin-Madison, Madison, USA.
Vet Med Sci. 2025 Sep;11(5):e70535. doi: 10.1002/vms3.70535.
This study set out to investigate kidney damage by examining the levels of key proteins-HIF-2α, COX-2 and IFN-γ in rats with disrupted circadian rhythms. It also explored how fish oil and flaxseed oil might influence the intensity of inflammation and its effects on kidney health.
Circadian rhythm disorder model groups consisted of eight rats each. Except for the control group, other groups (circadian rhythm, flaxseed oil and fish oil groups) were exposed to an adjustable light/dark cycle for 19 days, while the control group was kept on a standard light/dark cycle. In addition to standard food and water ad libitum nutrition for 19 days in four groups, 1000 mg/kg/day flaxseed oil was given to the flaxseed oil group and 400 mg/kg/day fish oil was given to the fish oil group by gavage for 19 days. Histological lesions in tissues were evaluated by Haematoxylin-Eosin staining and using a sequential grading system. For immunohistochemical analysis, IFN-γ, COX-2 and HIF-2 antibodies were used to evaluate the degree of immunohistochemical reactivity of the cells.
Nutrition unequivocally plays a critical role in regulating circadian rhythms, as factors such as meal timing, nutrient composition and gut health directly influence the body's internal clock and overall rhythm stability. Omega-3 fatty acids are known to influence immune, inflammatory and neurological pathways-all of which are controlled by the circadian clock. When circadian rhythms are disrupted, key signalling proteins such as HIF-2α, COX-2 and IFN-γ become dysregulated, leading to potential kidney damage. Remarkably, treatments with fish oil and flaxseed oil have been shown to reduce inflammation markers, effectively mitigating kidney damage and offering significant anti-inflammatory benefits. These results emphasize the aptitude of incorporating fish oil and flaxseed oil into the diet as a powerful strategy to combat kidney damage and slow the pathological effects caused by circadian rhythm disruption.
Circadian rhythm disturbances are associated with various health problems, including kidney damage characterized by microhaemorrhage and inflammatory cell infiltration. In this study, fish oil and flaxseed oil demonstrated protective, anti-inflammatory effects by reducing levels of HIF-2α, COX-2 and IFN-γ and improving kidney pathology. These effects were evaluated within the scope of an animal model, and the findings provide valuable preliminary data for future human studies.
本研究旨在通过检测昼夜节律紊乱大鼠体内关键蛋白——低氧诱导因子-2α（HIF-2α）、环氧化酶-2（COX-2）和干扰素-γ（IFN-γ）的水平来研究肾脏损伤情况。同时，本研究还探讨了鱼油和亚麻籽油如何影响炎症强度及其对肾脏健康的影响。
昼夜节律紊乱模型组每组有8只大鼠。除对照组外，其他组（昼夜节律组、亚麻籽油组和鱼油组）暴露于可调节的光/暗循环环境中19天，而对照组维持标准的光/暗循环。四组大鼠均自由摄取标准食物和水19天，亚麻籽油组通过灌胃给予1000 mg/kg/天的亚麻籽油，鱼油组给予400 mg/kg/天的鱼油，持续19天。通过苏木精-伊红染色并使用连续分级系统评估组织中的组织学损伤。对于免疫组织化学分析，使用IFN-γ、COX-2和HIF-2抗体评估细胞的免疫组织化学反应程度。
营养在调节昼夜节律中无疑起着关键作用，因为进餐时间、营养成分和肠道健康等因素直接影响身体的生物钟和整体节律稳定性。已知ω-3脂肪酸会影响免疫、炎症和神经通路——所有这些都受昼夜节律时钟控制。当昼夜节律紊乱时，HIF-2α、COX-2和IFN-γ等关键信号蛋白会失调，导致潜在的肾脏损伤。值得注意的是，鱼油和亚麻籽油治疗已被证明可降低炎症标志物，有效减轻肾脏损伤并提供显著的抗炎益处。这些结果强调了将鱼油和亚麻籽油纳入饮食作为对抗肾脏损伤和减缓昼夜节律紊乱引起的病理影响的有力策略的适用性。
昼夜节律紊乱与各种健康问题相关，包括以微出血和炎症细胞浸润为特征的肾脏损伤。在本研究中，鱼油和亚麻籽油通过降低HIF-2α、COX-2和IFN-γ水平并改善肾脏病理表现出保护和抗炎作用。这些作用是在动物模型范围内评估的，研究结果为未来的人体研究提供了有价值的初步数据。
