Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury
Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury
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DOI：
10.1111/j.1440-1746.2010.06323.x
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Davidson, Brian R.
中科院分区：
文献类型：
--
作者：
Sheth, Hemant;Hafez, Tariq;Davidson, Brian R.
背景与目的：实验研究表明非必需氨基酸甘氨酸对肝脏缺血再灌注（I/R）损伤具有保护作用，但其作用机制尚不清楚。方法：采用兔肝大叶I/R模型。研究三组动物（n = 6）：假手术组（单独开腹）、缺血再灌注（I/R）组（肝叶缺血1 h再灌注6 h）和甘氨酸I/R组（I/R方案前静脉注射甘氨酸5 mg/kg）。实验期间测量了全身和肝脏血流动力学、肝损伤程度（胆汁流量、转氨酶）、肝脏微循环、线粒体活性（细胞色素氧化酶氧化还原状态）、胆汁成分和细胞因子（肿瘤坏死因子- α和白细胞介素-8）。结果：与I/R组相比，甘氨酸增加了再灌注时的门静脉血流、胆汁生成、肝脏微循环和维持细胞色素氧化酶活性。与I/R组相比，甘氨酸还减少了再灌注时胆汁中乳酸激增和刺激乙酰乙酸释放。细胞因子水平（肿瘤坏死因子- α、白细胞介素-8）和肝细胞损伤（天冬氨酸转氨酶和丙氨酸转氨酶）均显著降低。结论：静脉给药甘氨酸通过降低全身炎症反应和维持细胞能量生成来减轻肝脏热I/R损伤。
Background and Aim:Experimental studies have shown protective effect by the non-essential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the mechanism of action is unknown.Methods:A rabbit model of hepatic lobar I/R was used. Three groups of animals (n = 6) were studied: Sham group (laparotomy alone), ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile flow, transaminases), hepatic microcirculation, mitochondrial activity (redox state of cytochrome oxidase), bile composition and cytokines (tumor necrosis factor-alpha and interleukin-8) were measured during the experiment.Results:Glycine administration increased portal blood flow, bile production, hepatic microcirculation and maintained cytochrome oxidase activity as compared with the I/R group during reperfusion. Glycine also reduced bile lactate surge and stimulated acetoacetate release in bile during reperfusion versus the I/R group. Cytokine levels (tumor necrosis factor-alpha, interleukin-8) and hepatocellular injury (aspartate aminotransferase and alanine aminotransferase) were significantly reduced by glycine administration.Conclusion:Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.