迷走神经-α7nAChR-IL-22通路对急性肝损伤的保护作用。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-01 DOI:10.1016/j.cyto.2024.156840

Zhihao Song , Jing Wu , Tiemin Jiang , Rongdong He , Hao Wen

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引用次数: 0

摘要

背景：急性肝损伤是各种临床疾病的共同病理特征，肝损伤延长可导致肝纤维化甚至肝衰竭。有研究报道迷走神经可通过调节胆碱能抗炎通路修复肝损伤。然而，关于白细胞介素-22的调控及其在肝损伤中的作用的研究有限。本研究旨在探讨迷走神经受体α7nAChR对白细胞介素-22的调控作用，以及该调控轴是否对肝损伤具有保护作用。方法：采用四氯化碳对大鼠和人肝细胞L-02进行急性肝损伤模拟。实验组分为：对照组、模型组、模型+ PNU282987组、模型+ MLA组、MLA组。干预后，采用实时荧光定量PCR、Western blot、免疫组化和ELISA等方法，检测小鼠的肝功能（AST、ALT）、炎症（TNF-α、IL-6、）、α7nAChR和白细胞介素-22浓度、凋亡水平（Bax、BCL-2）和增殖标志物（Ki-67、PCNA）。结果：结果表明，四氯化碳干预导致白细胞介素-22代偿性升高，而α7nAChR抑制使白细胞介素-22浓度降低，并加重以高水平AST、ALT、TNF-α、IL-6为标志的损伤。外源性迷走神经激动剂可减轻肝损伤，并伴有白细胞介素-22水平升高。在救援实验中，同时抑制迷走神经受体和外源性白细胞介素-22可减轻肝损伤，显著增强肝再生。相反，在抑制白细胞介素-22的同时，迷走神经受体的激活加重了肝损伤。结论：本研究证实迷走神经受体α7nAChR通过调节白细胞介素-22促进肝脏再生，对四氯化碳诱导的肝损伤具有保护作用。

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The protective effect of the vagus nerve-α7nAChR-IL-22 pathway on acute liver injury

Background

Acute liver injury is a common pathological feature of various clinical diseases, and prolonged liver damage can lead to fibrosis and even liver failure. Studies have reported that the vagus nerve can repair liver injury through the regulation of the cholinergic anti-inflammatory pathway. However, there is limited research on the regulation of interleukin-22 and its role in liver injury. This study aimed to investigate the regulatory effect of vagus nerve receptor α7nAChR on interleukin-22 and whether this regulatory axis can protect against liver injury.

Methods

Rats and the human liver cell line L-02 were treated with carbon tetrachloride to simulate acute liver injury. The experimental groups were divided as follows: control group, model group, model + PNU282987 group, model + MLA group, and MLA group. After the intervention, blood samples, liver tissues, and cells were collected to assess liver function (AST, ALT), inflammation (TNF-α, IL-6,), α7nAChR and interleukin-22 concentrations, apoptosis levels (Bax, BCL-2), and proliferation markers (Ki-67, PCNA) using quantitative real time PCR, Western blot, immunohistochemistry and ELISA.

Results

The results indicated that carbon tetrachloride intervention led to compensatory increases in interleukin-22 while inhibition of α7nAChR decreased interleukin-22 concentrations and exacerbated the injury marked by high levels of AST, ALT and TNF-α,IL-6. Exogenous administration of a vagus nerve agonist alleviated liver injury and was accompanied by an increase in interleukin-22 levels. In rescue experiments, simultaneous inhibition of vagus nerve receptors and administration of exogenous interleukin-22 reduced liver injury and significantly enhanced liver regeneration. Conversely, activation of vagus nerve receptors while inhibiting interleukin-22 aggravated liver injury.

Conclusion

This study confirms that vagus nerve receptor α7nAChR can promote liver regeneration and protect against carbon tetrachloride-induced liver injury by regulating interleukin-22.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.