Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy.
Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy.
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DOI：
10.1111/j.1872-034x.2012.01030.x
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Nguyen JH
中科院分区：
文献类型：
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作者：
Gardner LB;Hori T;Chen F;Baine AM;Hata T;Uemoto S;Nguyen JH
γ-氨基丁酸（GABA）是一种多功能分子，在全身具有各种生理作用。GABA受体（GABAR）的调节在减轻氧化应激（OS）介导的损伤中起着关键作用。扩大的肝切除术导致致命的OS诱导的损伤，在肝脏残余。我们的目的是研究GABAR激动剂在扩大肝切除术中的作用。术前4 h静脉注射生理盐水或GABAR激动剂（蝇蕈醇43.56 nmol/g体重）。将C57 BL/6小鼠分为三组：仅剖腹手术、用盐水进行90%肝切除术和用GABAR激动剂进行90%肝切除术。在手术后6 h获得肝脏样品。GABAR激动剂延长了生存曲线。组织学结果和生化特征表明，GABAR激动剂减少肝损伤。免疫组织学评估表明，GABAR激动剂防止凋亡诱导。如反映OS诱导的损伤的4-羟基壬烯醛所示，90%肝切除导致OS，GABAR激动剂降低OS。我们测量了ATM、H2 AX、Akt和自由基清除酶，因为它们可能受到GABAR调节的影响，发现Akt在90%肝切除后大大降低，但GABAR激动剂使其恢复。GABAR在体内由肝脏中的特异性激动剂激活。这种激活减少了体内扩大肝切除术后OS介导的损伤，并且通过Akt依赖性途径的机制可能是关键。
Gamma-aminobutyric acid (GABA) is a multifunctional molecule with various physiological effects throughout the body. The regulation of GABA receptor (GABAR) plays a key role in reducing the damage mediated by oxidative stress (OS). Extended hepatectomy causes fatal OS-induced injury in the liver remnant. We aimed to investigate the effect of a GABAR agonist in extended hepatectomy. Saline or a GABAR agonist (43.56 nmol/g body weight of muscimol) was given intravenously at 4 h preoperatively. C57BL/6 mice were divided into three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy with a GABAR agonist. Liver samples were obtained at 6 h after surgery. Survival curves were prolonged by the GABAR agonist. Histopathological findings and biochemical profiles showed that the GABAR agonist reduced liver damage. Immunohistological assessment demonstrated that the GABAR agonist prevented apoptotic induction. As shown by 4-hydroxynonenal, which reflects OS-induced damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured ATM, H2AX, Akt and free radical scavenging enzymes since they may be affected by GABAR regulation, and found that Akt was greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist. GABAR is activated by a specific agonist in the liver in vivo. This activation reduces OS-madiated damage after extended hepatectomy in vivo, and the mechanism via an Akt-dependent pathway may be a key.