Increased brain lactate is central to the development of brain edema in rats with chronic liver disease
Increased brain lactate is central to the development of brain edema in rats with chronic liver disease
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DOI：
10.1016/j.jhep.2013.10.011
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发表时间：
2014-03-01
影响因子：
25.7
通讯作者：
Rose, Christopher F.
中科院分区：
文献类型：
--
作者：
Bosoi, Cristina R.;Zwingmann, Claudia;Rose, Christopher F.
背景和目标：慢性肝病（CLD）和轻微肝性脑病（HE）患者脑水肿的发病机制尚未明确。本研究评估的作用，脑乳酸，谷氨酰胺和有机渗透，包括肌醇和牛磺酸，在脑水肿的发展中的大鼠模型cirrhosis.Methods：6周胆管结扎（BDL）大鼠注射C-13-葡萄糖和从头合成的乳酸，谷氨酰胺在脑中的定量使用C-13核磁共振波谱（NMR）。使用H-1 NMR或高效液相色谱法测定脑总乳酸、谷氨酰胺和渗透压。为了进一步明确乳酸、谷氨酰胺和脑水肿之间的相互作用，用AST-120（工程活性炭微球）和二氯乙酸（DCA：乳酸合成抑制剂）治疗BDL大鼠。
Background & Aims: The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis.Methods: Six-week bile-duct ligated (BDL) rats were injected with C-13-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using C-13 nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using H-1 NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor).Results: Significant increases in de nova synthesis of lactate (1.6-fold, p