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醋酸视黄醇对肝纤维化的影响取决于病理发展的时间特征。

The Effect of Retinol Acetate on Liver Fibrosis Depends on the Temporal Features of the Development of Pathology.

作者信息

Bozhkov Anatoly I, Akzhyhitov Rustam A, Bilovetska Svitlana G, Ivanov Evgeny G, Dobrianska Nataliia I, Bondar Anastasiia Yu

机构信息

Biology Research Institute V. N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv, 61022, Ukraine.

出版信息

J Clin Exp Hepatol. 2024 May-Jun;14(3):101338. doi: 10.1016/j.jceh.2023.101338. Epub 2023 Dec 21.

DOI:10.1016/j.jceh.2023.101338
PMID:38264572
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10801314/
Abstract

BACKGROUND

The effect of vitamin A on the manifestations of liver fibrosis is controversial and establishing the causes of its multidirectional influence is an urgent problem. In the work, the functional characteristics of the liver with Cu-induced fibrosis were determined after the restoration of vitamin A to the control level at the F0/F1 stage.

METHODS

In animals with liver fibrosis, classical indicators of physiology, functional activity of the liver, histological, and hematological characteristics were determined; the content of calcium and ROS was determined in bone marrow cells.

RESULTS

It was shown that in the liver with Cu-induced fibrosis, the restoration of vitamin A content to control values after injections of a retinol acetate solution at a dose of 0.10 mg (300 IU)/100 g of body weight in the early stages of this pathology development (Fо/F1) was accompanied by: a decrease in the number of immunocompetent cells in the bloodstream to control values; normalization of the amount of calcium ions and ROS in bone marrow cells; restoration to the control level of activity of alkaline phosphatase; an increase in the number of binuclear hepatocytes; and restoration of the dynamics of body weight growth in experimental animals, even against the background of the ongoing action of the hepatotoxic factor.

CONCLUSION

We came to the conclusion that the multidirectional action of vitamin A, which occurs in liver fibrosis, depends not only on the concentration of vitamin A in the liver but also on temporal characteristics of cellular and metabolic links involved in the adaptive response formation. It was suggested that knowledge of the initial temporal metabolic characteristics and the amount of vitamin A in the liver, taking into account the stages of fibrosis development, can be an effective way to restore the altered homeostatic parameters of the body.

摘要

背景

维生素A对肝纤维化表现的影响存在争议,确定其多向性影响的原因是一个紧迫的问题。在本研究中,在F0/F1阶段将维生素A恢复到对照水平后,测定了铜诱导纤维化肝脏的功能特性。

方法

测定肝纤维化动物的生理学经典指标、肝脏功能活性、组织学和血液学特征;测定骨髓细胞中的钙含量和活性氧水平。

结果

结果表明,在铜诱导纤维化的肝脏中,在该病理发展早期(Fо/F1)以0.10 mg(300 IU)/100 g体重的剂量注射醋酸视黄醇溶液后,将维生素A含量恢复到对照值,伴随着以下变化:血液中免疫活性细胞数量减少至对照值;骨髓细胞中钙离子和活性氧含量正常化;碱性磷酸酶活性恢复到对照水平;双核肝细胞数量增加;实验动物体重增长动态恢复,即使在肝毒性因子持续作用的背景下也是如此。

结论

我们得出结论,维生素A在肝纤维化中发生的多向作用不仅取决于肝脏中维生素A的浓度,还取决于参与适应性反应形成的细胞和代谢联系的时间特征。有人提出,考虑到纤维化发展阶段,了解肝脏中维生素A的初始时间代谢特征和含量,可能是恢复机体改变的稳态参数的有效方法。