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首页> 外文期刊>Journal of applied toxicology >Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury
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Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury

机译:肝γ-氨基丁酸信号传导在急性乙醇暴露诱导的肝损伤中的保护作用

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摘要

Abstract Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxyl-ase and type A GABA receptor (GABA_AR) subunits was upregulated in ethanol-treated mice compared with saline-treated controls. Remarkably, pretreatment of mice with GABA (1.5 mg kg"1 body weight, intraperitoneal injection [i.p.]) or with the GABA_AR agonist muscimol (1.2 mg kg"1 body weight, i.p.) protected the liver against ethanol toxicity and improved liver function, whereas pretreatment of mice with the GABA_AR antagonist bicuculline (2.0 mg kg"1 body weight, i.p.) worsened the liver function. Further analyses suggest that GABA_AR-mediated signaling protects the liver from ethanol injury by, at least partially, inhibiting the IRElalpha-ASKl-JNK pro-apoptotic pathway in hepatocytes in the process of ethanol-induced endoplasmic reticulum stress response.
机译:摘要含酒精肝病(ALD)是重度和延长的酒精消耗的结果。我们之前证明了一种肝脏γ-氨基丁酸(GABA)信号传导系统,可保护肝脏免受毒性损伤。本研究旨在探讨肝GABA信号系统在急性乙醇暴露诱导的肝损伤过程中的作用。我们的研究结果表明,与盐水处理的对照相比,在乙醇处理的小鼠中升高了GABA合成酶谷氨酸脱羧和型GABA受体(GABA_AR)亚基的表达。值得注意的是,用GABA的预处理(1.5mg kg“1体重,腹膜内注射[IP])或与GABA_AR激动剂uscimol(1.2mg kg”1体重,IP)保护肝脏毒性和改善肝功能,然而,用GABA_AR拮抗剂Biculline的预处理(2.0mg Kg“1体重,IP)恶化了肝功能。进一步分析表明GABA_AR介导的信号传导至少部分地保护肝脏免受乙醇损伤,抑制IRELPHA-ASKL -JNK肝细胞中的肝细胞凋亡途径在乙醇诱导的内质网应激应激响应过程中。

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