Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation.

Prednisolone has a positive effect on the kidney but not on the liver of brain dead rats: a potencial role in complement activation.
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DOI:
10.1186/1479-5876-12-111
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发表时间:
2014-05-02
影响因子:
7.4
通讯作者:
Leuvenink HG
Leuvenink HG
中科院分区:
医学2区
文献类型:
--
作者:
Rebolledo R;Liu B;Akhtar MZ;Ottens PJ;Zhang JN;Ploeg RJ;Leuvenink HG

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关于类固醇治疗对脑死亡(BD)供者肾和肝移植结果的影响,已经发表了相互矛盾的证据。我们的研究旨在通过研究泼尼松龙给药对BD大鼠的影响来评估这种差异。通过将Fogarty导管充气置于硬膜外腔,对通气大鼠进行BD诱导。强的松龙(22.5 mg/kg)在BD诱导前30分钟给予。BD测定4小时后,采集血清、肾、肝组织标本保存。进行RT-qPCR、常规生化及免疫组织化学检测。泼尼松龙治疗可降低循环IL-6和血浆肌酐水平,但不能降低血清AST、ALT或LDH水平。组织学评估的多形核内流和肾脏和肝脏的炎症基因表达减少。补体成分3(补体成分3,C3)在肾脏中表达降低,而在肝脏中表达不降低。治疗后肝脏细胞保护蛋白HSP-70基因表达下调。本研究表明,强的松龙可减轻炎症,改善肾功能,但不能减轻肝损伤。补体激活的持续性和对肝脏保护细胞机制的负面影响可能解释了强的松龙对BD大鼠肾脏和肝脏的作用差异。强的松龙给药在分子和细胞反应上的差异可能解释了强的松龙对来自脑死亡器官供体的不同器官类型影响的相互矛盾的证据。
Contradictory evidence has been published on the effects of steroid treatments on the outcomes of kidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate this disparity by investigating the effect of prednisolone administration on BD rats. BD induction was performed in ventilated rats by inflating a Fogarty catheter placed in the epidural space. Prednisolone (22.5 mg/kg) was administered 30 min prior to BD induction. After four hours of determination of BD: serum, kidney and liver tissues samples were collected and stored. RT-qPCR, routine biochemistry and immunohistochemistry were performed. Prednisolone treatment reduced circulating IL-6 and creatinine plasma levels but not serum AST, ALT or LDH. Polymorphonuclear influx assessed by histology, and inflammatory gene expression were reduced in the kidney and liver. However, complement component 3 (C3) expression was decreased in kidney but not in liver. Gene expression of HSP-70, a cytoprotective protein, was down-regulated in the liver after treatment. This study shows that prednisolone decreases inflammation and improves renal function, whilst not reducing liver injury. The persistence of complement activation and the negative effect on protective cellular mechanisms in the liver may explain the disparity between the effects of prednisolone on the kidney and liver of BD rats. The difference in the molecular and cellular responses to prednisolone administration may explain the contradictory evidence of the effects of prednisolone on different organ types from brain dead organ donors.
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