Influence of constant lighting on the morphofunctional state and rhythmostasis of the liver of rats

S. Grabeklis, L. Mikhaleva, M. A. Kozlova, D. Areshidze, A. Dygai
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Abstract

BACKGROUND: There are evidences that light pollution, which causes melatonin deficiency and disruption of circadian rhythm, is associated with the development of malignant neoplasms of the liver, non-alcoholic fatty liver disease, biliary cirrhosis, and a number of other pathologies of this organ. AIM: The aim of research was to study the features of chronic influence of constant lighting on lability of morphofunctional state of liver of mature Wistar rats and the structure of circadian rhythms of its parameters. MATERIALS AND METHODS: The study was conducted on 80 rats divided into 2 groups: a control group kept under a fixed light regime (light/dark 12/12 h, lights on at 8:00 and off at 20:00), and an experimental group kept under constant lighting 24 h a day. The duration of the experiment was 3 weeks. RESULTS: Its established that influence of constant light led to an increase in the size of hepatocytes and a decrease in nuclear-cytoplasmic ratio, average ploidy and proportion of binuclear hepatocytes, and also to development of fatty degeneration, a decrease in the expression of Bmal1 and Clock, and an increase in the expression of per2 and p53 in hepatocytes. At the same time, there was a decrease in glycogen content in hepatocytes. Dark deprivation also caused an increase in glucose levels, AST activity, and a decrease in blood levels of total protein and albumin. Constant lighting caused a rearrangement of the circadian rhythms of the area of nuclei, the area of the hepatocyte and nuclear-cytoplasmic ratio, Bmal1, per2, Clock expression, and led to destruction of Ki67 and p53 circadian rhythms in hepatocytes. Under conditions of constant lighting, the circadian rhythms of the content of lipids and glycogen in hepatocytes, ALT activity in the blood, and the content of total and direct bilirubin were also destroyed. CONCLUSIONS: It has been established that constant illumination causes a restructuring of the circadian rhythms of a number of studied parameters against the background of morphological and functional changes, indicating a decrease in the adaptive capacity of the liver.
恒定光照对大鼠肝脏形态功能状态及节律稳定的影响
背景:有证据表明,光污染导致褪黑激素缺乏和昼夜节律紊乱,与肝脏恶性肿瘤、非酒精性脂肪肝、胆汁性肝硬化和许多其他肝脏病理的发展有关。目的:研究持续光照对成年Wistar大鼠肝脏形态功能状态不稳定性及其参数昼夜节律结构的慢性影响特点。材料与方法:将80只大鼠分为2组,对照组为固定光照(12/12小时亮/暗,8:00开灯,20:00关灯),实验组为24小时恒定光照。试验期为3周。结果:确定恒定光的影响导致肝细胞体积增大,核质比、平均倍性和双核肝细胞比例降低,脂肪变性发生,Bmal1和Clock表达降低,per2和p53表达升高。同时,肝细胞糖原含量降低。黑暗剥夺还会导致葡萄糖水平、谷草转氨酶活性升高,以及血液中总蛋白和白蛋白水平下降。持续光照导致核区、肝细胞区、核质比、Bmal1、per2、Clock表达的昼夜节律重排,并导致肝细胞中Ki67和p53昼夜节律的破坏。在持续光照条件下,肝细胞中脂质和糖原含量、血液中ALT活性、总胆红素和直接胆红素含量的昼夜节律也被破坏。结论:已经确定,在形态学和功能改变的背景下,持续的光照会导致肝脏的生理节律发生重构,表明肝脏的适应能力下降。
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