The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Physiol Res. 2019 Oct 25;68(5):739-745. doi: 10.33549/physiolres.934095. Epub 2019 Aug 19.
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.
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。