Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats
Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats
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牛磺熊去氧胆酸和4-苯基丁酸减轻大鼠心死亡肝移植后内质网应激并改善捐献预后
DOI：
10.1016/s1499-3872(14)60269-1
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发表时间：
2014-12-15
影响因子：
3.3
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Lu, Hao;Lu, Ling;Zhang, Feng
背景：器官切取前不可避免的热缺血时间加重了移植后缺血再灌注损伤。内质网应激（endoplasmic reticulum，ER）参与了缺血再灌注损伤，但其在心脏死亡（cardiac death，DCD）肝移植供者中的作用尚不清楚，ER应激抑制剂牛磺熊去氧胆酸（tauroursodeoxycholic acid，TUDCA）和4-苯基丁酸（4-phenyl butyric acid，PBA）对DCD肝移植受者预后的影响尚不清楚。雄性Sprague-Dawley大鼠将8-10周的大鼠随机分为对照组、DCD组、TUDCA组和PBA组，每组10只。在DCD组的基础上，于器官切取前30 min腹腔注射TUDCA或PBA。评价血清转氨酶水平、氧化应激活化和ER应激信号分子的表达。进行病理学检查。结果：术后6 h、1d、3d，DCD组大鼠血清转氨酶水平明显高于对照组（P
BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia-reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear.METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P