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间歇性禁食和饮食限制对胆总管结扎模型中氧化还原状态、能量代谢及肝损伤的影响

Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.

作者信息

Semenovich Dmitry S, Zorova Ljubava D, Abramicheva Polina A, Andrianova Nadezda V, Elchaninov Andrey V, Petrukhina Aleksandra S, Pevzner Irina B, Manskikh Vasily N, Zorov Dmitry B, Plotnikov Egor Y

机构信息

A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia.

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117198 Moscow, Russia.

出版信息

Antioxidants (Basel). 2024 Jul 12;13(7):835. doi: 10.3390/antiox13070835.

Abstract

The aim of this work was to test whether we can treat cholestasis with dietary approaches applied after the onset of the disease. The effects of intermittent fasting and dietary restriction on liver damage caused by common bile duct ligation (BDL) in rats were studied, with particular attention paid to changes in the activity of enzymes of energy metabolism and antioxidant protection. Morphological changes in liver tissue and serum markers of liver damage were assessed in rats with BDL kept for one month on ad libitum diet, intermittent fasting, or 35% dietary restriction. We studied parameters of glucose metabolism (activity of glycolysis and gluconeogenesis enzymes), TCA cycle, and indicators of oxidative stress and redox status of the liver tissue. Dietary restriction resulted in an increase in gluconeogenesis activity, antioxidant capacity, and autophagy activation. When implemented after BDL, none of the dietary restriction protocols reduced the level of oxidative stress, detrimental morphological and biochemical alterations, or the fibrosis progression. Thus, under severe damage and oxidative stress developing in cholestasis, dietary restrictions are not hepatoprotective and can only be used in a pre-treatment mode.

摘要

这项工作的目的是测试在疾病发作后应用饮食方法是否能够治疗胆汁淤积症。研究了间歇性禁食和饮食限制对大鼠胆总管结扎(BDL)所致肝损伤的影响,特别关注能量代谢酶和抗氧化保护酶活性的变化。对自由采食、间歇性禁食或35%饮食限制的BDL大鼠饲养1个月后,评估其肝组织的形态学变化和肝损伤血清标志物。我们研究了葡萄糖代谢参数(糖酵解和糖异生酶的活性)、三羧酸循环以及肝组织氧化应激和氧化还原状态指标。饮食限制导致糖异生活性增加、抗氧化能力增强和自噬激活。在BDL后实施时,没有一种饮食限制方案能降低氧化应激水平、有害的形态学和生化改变或纤维化进展。因此,在胆汁淤积症中出现严重损伤和氧化应激时,饮食限制没有肝脏保护作用,只能在预处理模式下使用。

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