Liver graft pretreated in vivo or ex vivo by γ-aminobutyric acid receptor regulation.
Liver graft pretreated in vivo or ex vivo by γ-aminobutyric acid receptor regulation.
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DOI：
10.1016/j.jss.2012.08.055
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发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Nguyen JH
中科院分区：
文献类型：
--
作者：
Hori T;Gardner LB;Chen F;Baine AM;Hata T;Uemoto S;Nguyen JH
γ-氨基丁酸存在于全身，脑γ-氨基丁酸受体（GABAR）调节降低氧化应激（OS）。肝脏中GABAR调节的影响尚不清楚。原位肝移植（奥尔特）后的缺血或再灌注损伤或小尺寸移植物劈裂奥尔特（SOLT）后的切应力导致OS诱导的移植物损伤。在这里，研究了通过GABAR调节在体内和离体移植物预处理的战略潜力。根据移植物预处理和移植物类型，将Wistar大鼠分为7组：（1）剖腹手术组，（2）奥尔特组，（3）GABAR调节体内和奥尔特组，（4）GABAR调节离体和奥尔特组，（5）SOLT组，（6）GABAR调节体内和SOLT组，（7）GABAR调节离体和SOLT组。在奥尔特或SOLT后6 h进行生存研究、生化测定、组织病理学或免疫组织学评估和Western印迹。体内移植预处理延长SOLT后的存活。组织学和生物化学资料证实，移植物预处理在体内减少奥尔特或SOLT后的移植物损伤。在免疫组织学上，移植物预处理在体内阻止了奥尔特或SOLT后的凋亡诱导。4-羟基壬烯醛证实了奥尔特或SOLT后的OS，体内移植物预处理改善了OS。体内移植物预处理降低了奥尔特或SOLT后共济失调毛细血管扩张突变激酶和H2 AX。移植物预处理增加了SOLT后的磷脂酰肌醇3激酶和Akt。相反，GABAR调节离体不起作用。移植物预处理在体内，而不是离体，防止缺血或再灌注损伤介导的OS后OLT或SOLT通过共济失调毛细血管扩张突变激酶/H2 AX途径和剪切应力介导的OS后SOLT与小尺寸移植物通过磷脂酰肌醇3激酶/Akt途径。
γ-Aminobutyric acid exists throughout the body, and the brain γ-aminobutyric acid receptor (GABAR) regulation reduces oxidative stress (OS). Effects of GABAR regulation in the liver are unknown. Ischemia or reperfusion injury after orthotopic liver transplantation (OLT) or shear stress after split OLT (SOLT) with a small-for-size graft causes OS-induced graft damage. Here, the strategic potential of graft pretreatment in vivo and ex vivo by GABAR regulation was investigated. Recipient rats were divided into seven groups according to the graft pretreatments and graft types: (1) laparotomy, (2) OLT, (3) GABAR regulation in vivo and OLT, (4) GABAR regulation ex vivo and OLT, (5) SOLT, (6) GABAR regulation in vivo and SOLT, and (7) GABAR regulation ex vivo and SOLT. Survival study, biochemical assays, histopathologic or immunohistologic assessments, and Western blotting were performed at 6 h after OLT or SOLT. Graft pretreatment in vivo prolonged survival after SOLT. Histopathologic and biochemical profiles verified that graft pretreatment in vivo reduced graft damage after OLT or SOLT. Immunohistologically, graft pretreatment in vivo prevented apoptotic inductions after OLT or SOLT. The 4-hydroxynonenal confirmed the OS after OLT or SOLT, and graft pretreatment in vivo improved the OS. Graft pretreatment in vivo decreased ataxia-telangiectasia–mutated kinase and H2AX after OLT or SOLT. Graft pretreatment in vivo increased phosphatidylinositol 3 kinase and Akt after SOLT. In contrast, GABAR regulation ex vivo did not work. Graft pretreatment in vivo, not ex vivo, prevented the ischemia or reperfusion injury–mediated OS after OLT or SOLT via the ataxia-telangiectasia–mutated kinase/H2AX pathway and the shear stress–mediated OS after SOLT with small-for-size graft via the phosphatidylinositol 3 kinase/Akt pathway.
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