Effect of rifampicin on TLR4-signaling pathways in the nucleus accumbens of the rat brain during abstinence of long-term alcohol treatment.

IF 2.1 4区医学 Q3 SUBSTANCE ABUSE

Alcohol and alcoholism Pub Date : 2024-03-16 DOI:10.1093/alcalc/agae016

Marat Airapetov, Sergei Eresko, Polina Ignatova, Andrei Lebedev, Evgenii Bychkov, Petr Shabanov

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引用次数: 0

Abstract

Aims: The treatment with the antibiotic rifampicin (Rif) led to a decrease in the frequency of neurodegenerative pathologies. There are suggestions that the mechanism of action of Rif may be mediated by its effect on toll-like receptor (TLR)4-dependent pathways. We evaluated the expression status of TLR4-dependent genes during abstinence from long-term alcohol treatments in the nucleus accumbens (NAc) of the rat brain, and also studied the effects of Rif to correct these changes.

Methods: The long-term alcohol treatment was performed by intragastric delivery of ethanol solution. At the end of alcohol treatment intraperitoneal injections of Rif (100 mg/kg) or saline were made. Extraction of the brain structures was performed on the 10th day of abstinence from alcohol. We used the SYBR Green qPCR method to quantitatively analyze the relative expression levels of the studied genes.

Results: The long-term alcohol treatment promotes an increase in the level of TLR4 mRNA and mRNA of its endogenous ligand high-mobility group protein B1 during abstinence drop alcohol in NAc of rats. The use of Rif in our study led to a decrease in the increased expression of high-mobility group protein B1, Tlr4, and proinflammatory cytokine genes (Il1β, Il6) in the NAc of the rat brain during abstinence of long-term alcohol treatment. In addition, Rif administration increased the decreased mRNA levels of anti-inflammatory cytokines (Il10, Il11).

Conclusion: The data obtained indicate the ability of Rif to correct the mechanisms of the TLR4 system genes in the NAc of the rat brain during alcohol abstinence.

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利福平对长期戒酒大鼠脑内伏隔核 TLR4 信号通路的影响

目的：使用抗生素利福平（Rif）治疗可降低神经退行性病变的发生率。有观点认为，利福平的作用机制可能是通过其对依赖于收费样受体（TLR）4的途径的影响而介导的。我们评估了大鼠大脑中长期戒酒后核（NAc）内TLR4依赖基因的表达状况，并研究了Rif对纠正这些变化的作用：方法：通过胃内注射乙醇溶液对大鼠进行长期酒精治疗。方法：通过胃内注射乙醇溶液对大鼠进行长期酒精治疗，在酒精治疗结束后腹腔注射利福君（100 毫克/千克）或生理盐水。在戒酒第 10 天提取大脑结构。我们使用 SYBR Green qPCR 方法定量分析了所研究基因的相对表达水平：结果：长期酒精治疗会促进大鼠NAc中TLR4 mRNA及其内源配体高迁移率基团蛋白B1 mRNA水平的升高。在我们的研究中，使用 Rif 可降低长期戒酒大鼠大脑 NAc 中高迁移率组蛋白 B1、Tlr4 和促炎细胞因子基因（Il1β、Il6）的表达。此外，利福君还能增加抗炎细胞因子（Il10、Il11）mRNA水平的下降：结论：所获得的数据表明，利福能够在戒酒期间纠正大鼠大脑NAc中TLR4系统基因的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcohol and alcoholism 医学-药物滥用

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

4-8 weeks

期刊介绍： About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.