褪黑素和体育锻炼对继发性胆汁性肝硬化的影响

IF 4.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Annals of hepatology Pub Date : 2025-09-01 DOI:10.1016/j.aohep.2025.101973

Marilda da Silva Brasil , Elizângela Gonçalves Schemitt , Sandielly Rebeca Benitez da Fonseca , Gabriela dos Santos Martins , Millena de Oliveira Engeroff , Giorgia Assoni , Lorenzo Cercal Britto , Cláudio Augusto Marroni , Norma Possa Marroni

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引用次数: 0

摘要

简介与目的肝硬化的特点是肝实质内形成间隔和纤维化结节，是一个相关的公共卫生问题。胆管结扎术（BDL）是诱导继发性胆汁性肝硬化的有效实验模型。褪黑素（MLT）具有抗氧化、抗纤维化和细胞保护特性。体育锻炼（EX）已显示出对不同疾病的有益作用。探讨MLT和EX对bdl诱导大鼠胆汁性肝硬化的影响。材料与方法本研究已通过CEUA/HCPA（2021-0642）批准。选用雄性Wistar大鼠26只（60 d，±350g），分为CO组、BDL组、BDL+MLT组和BDL+EX组。实验组于第1天进行BDL。从第15天开始，给予MLT （20 mg/kg/天），并开始游泳方案。第29天采集血液（用于分析AST、ALT和FA）和肝脏。数据采用Student-Newman-Keuls后验单因素方差分析（mean±SE; p<0.05）。结果LDB组ast、ALT、FA较CO组显著升高（p < 0.05）， LDB+MLT和LDB+EX组显著降低（p < 0.05）。小天狼星染色显示LDB组纤维化强烈，经治疗后纤维化减弱。GPx活性在LDB组降低（p<0.01），但随MLT和EX升高。CAT在LDB组升高，随处理降低（p<0.05）。LDB组一氧化氮水平升高，MLT组降低。结论smlt和EX对胆汁性肝硬化大鼠肝脏具有保护作用，可减轻肝脏生化、氧化和纤维化变化。

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EFFECTS OF MELATONIN AND PHYSICAL EXERCISE ON SECONDARY BILIARY CIRRHOSIS

Introduction and Objectives

Cirrhosis is characterized by the formation of septa and fibrotic nodules in the liver parenchyma, and it is a relevant public health problem. Bile duct ligation (BDL) is an effective experimental model for inducing secondary biliary cirrhosis. Melatonin (MLT) has antioxidant, antifibrotic, and cytoprotective properties. Physical exercise (EX) has shown beneficial effects in different diseases.

To investigate the effects of MLT and EX on BDL-induced biliary cirrhosis in rats.

Materials and Methods

The study, was approved by CEUA/HCPA (2021-0642). We used 26 male Wistar rats (60 days, ±350g), distributed into four groups: CO, BDL, BDL+MLT, and BDL+EX. BDL was performed on day 1 in the experimental groups. From the 15th day onwards, MLT (20 mg/kg/day) was administered and the swimming protocol was started. On the 29th day, blood (for analysis of AST, ALT and FA) and liver were collected. Data were analyzed by One-Way ANOVA with Student-Newman-Keuls post-test (mean±SE; p<0.05).

Results

AST, ALT and FA were increased significantly in the LDB group vs. CO (p<0.05), with reduction in the LDB+MLT and LDB+EX groups (p<0.05). The Picrosirius staining indicated intense fibrosis in the LDB group, this effect was attenuated by treatments. GPx activity was reduced in the LDB group (p<0.01), but increased with MLT and EX. CAT increased in the LDB group and decreased with treatments (p<0.05). Nitric oxide levels increased in the LDB group and decreased with MLT.

Conclusions

MLT and EX promoted protective effects in the liver of rats with biliary cirrhosis, attenuating biochemical, oxidative and fibrotic changes.

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来源期刊

Annals of hepatology 医学-胃肠肝病学

CiteScore

7.90

自引率

2.60%

发文量

183

审稿时长

4-8 weeks

期刊介绍： Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.