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α-硫辛酸对成年雄性大鼠部分肝缺血再灌注损伤的保护作用及机制。

Protective effect and mechanism of alpha-lipoic acid on partial hepatic ischemia-reperfusion injury in adult male rats.

机构信息

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

出版信息

Physiol Res. 2019 Oct 25;68(5):739-745. doi: 10.33549/physiolres.934095. Epub 2019 Aug 19.

Abstract

In order to reduce tissue damage caused by ischemia-reperfusion injury, this study aims to investigate the protective effect and mechanism of ?-lipoic acid on hepatic ischemia-reperfusion injury in rats. The bloodstream of rats was blocked in the left middle and left lateral liver lobes of the liver. Forty rats were randomly divided into two groups: treatment group and injury group. Rats were injected with either 25 mg/1 ml of alpha-lipoic acid (treatment group) or 1 ml of saline (injury group) into the caudal vein 15 min before hepatic ischemia-reperfusion. Rat serum alanine aminotransferase (GPT), glutathione (GSH) and superoxide dismutase (SOD) levels were examined at various time points (1, 3, 6 and 12 h) in both groups. Changes in nuclear factor kappa B P65 (NF-kappaB P65) expression in ischemia-reperfusion liver at various time points after reperfusion (1, 3, 6 and 12 h) were evaluated through immunohistochemistry assay. Changes in macrophage inflammatory protein-2 (MIP-2) mRNA and inducible nitric oxide synthase (iNOS) mRNA expression in ischemic reperfused rat livers were detected by RT-PCR. Serum GPT level was significantly higher in the injury group than in the treatment group (P<0.01). NF-kappaB P65, MIP-2 mRNA and iNOS mRNA expression in ischemic reperfused rat livers were significantly higher in the injury group than in the treatment group (P<0.01). Serum GSH and SOD levels were higher in the treatment group than in the injury group (P<0.01). Alpha-lipoic acid significantly reduced ischemia-reperfusion injury in rat livers. This may be associated to the direct scavenging of oxygen-free radicals, increased GSH production, and the activation of downstream media due to decreased NF-kappaB and GSH consumption.

摘要

为了减少缺血再灌注损伤引起的组织损伤,本研究旨在探讨 α-硫辛酸对大鼠肝缺血再灌注损伤的保护作用及其机制。阻断大鼠肝左中叶和左外侧叶的血流。40 只大鼠随机分为两组:治疗组和损伤组。肝缺血再灌注前 15 分钟,治疗组大鼠尾静脉注射 25mg/1mlα-硫辛酸(治疗组),损伤组大鼠尾静脉注射 1ml 生理盐水。分别于再灌注后 1、3、6、12h 检测两组大鼠血清丙氨酸氨基转移酶(GPT)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平。通过免疫组织化学法检测再灌注后不同时间点(1、3、6、12h)缺血再灌注肝核因子-κB P65(NF-κB P65)表达的变化。用 RT-PCR 检测缺血再灌注大鼠肝巨噬细胞炎性蛋白-2(MIP-2)mRNA 和诱导型一氧化氮合酶(iNOS)mRNA 的表达变化。损伤组大鼠血清 GPT 水平明显高于治疗组(P<0.01)。损伤组大鼠肝缺血再灌注后 NF-κB P65、MIP-2mRNA 和 iNOSmRNA 的表达明显高于治疗组(P<0.01)。治疗组大鼠血清 GSH 和 SOD 水平明显高于损伤组(P<0.01)。α-硫辛酸可显著减轻大鼠肝缺血再灌注损伤。这可能与直接清除氧自由基、增加 GSH 生成以及 NF-κB 减少和 GSH 消耗激活下游介质有关。

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