Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys
Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys
复制标题
保存液和自体血液灌流液中的环螺旋 B 肽可改善离体猪肾的缺血再灌注损伤
DOI：
10.1097/txd.0000000000000515
复制
发表时间：
2015-03-01
影响因子：
2.3
通讯作者：
Yang, Bin
中科院分区：
文献类型：
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作者：
Yang, Cheng;Hosgood, Sarah A.;Yang, Bin
背景在移植前，迫切需要更好地保存离体器官。我们开发了一种新的非红细胞生成的环螺旋B肽（CHBP）衍生的促红细胞生成素，它具有强大的组织保护和延长血清稳定性。在肾脏保存模型上评价CHBP的肾脏保护作用及其可能机制。材料与方法取热缺血20分钟的猪肾（n = 5），用高渗性柠檬酸盐冲洗以模拟死者捐献。将肾脏和自体血± 10.56 nmol/L CHBP置于冷藏（CS）18小时。然后使用离体器官灌注系统对这些肾脏进行常温血液再灌注3小时。检测肾功能、肾组织结构、细胞凋亡、炎症反应、caspase-3和热休克蛋白70（HSP 70）的表达。结果环螺旋B肽可明显增加再灌注时肾血流量、氧耗量和尿量，降低血钾和肾组织损伤。凋亡细胞显着减少，但在管腔和间质区后CS和后灌注肾，而髓过氧化物酶+细胞减少。此外，在再灌注肾脏中，CHBP下调caspase-3前体和活性亚基的表达。然而，HSP 70在CS后和用CHBP处理的灌注后的肾脏中上调。结论环螺旋B肽可减轻大鼠肾缺血再灌注损伤，其机制可能与减少细胞凋亡、炎症反应和caspase-3的表达，增加HSP 70的表达有关。这种使用CHBP的新保存方法可应用于猪肾移植模型和潜在的人类供体肾保存。
Background There is a critical need to better preserve isolated organs before transplantation. We developed a novel nonerythropoiesis cyclic helix B peptide (CHBP) derived from erythropoietin, which has potent tissue protection and prolonged serum stability. The renoprotection and potential mechanism of CHBP were evaluated in a kidney preservation model. Materials and Methods Porcine kidneys (n = 5) subjected to 20-minute warm ischemia were retrieved and flushed with hyperosmolar citrate to mimic deceased donation. The kidneys and autologous blood ± 10.56 nmol/L CHBP were placed in cold storage (CS) for 18 hours. These kidneys were then normothermically hemoreperfused for 3 hours using an isolated organ perfusion system. The renal function and structure, apoptosis, inflammation, and expression of caspase-3 and heat shock protein 70 (HSP70) were assessed. Results Cyclic helix B peptide significantly increased the renal blood flow, oxygen consumption, and urine output during reperfusion, but decreased serum potassium and renal tissue damage. Apoptotic cells were significantly decreased in the tubular areas, but increased in the lumens and interstitial areas in the post-CS and postreperfused kidneys, whereas myeloperoxidase+ cells were reduced. In addition, the expression of both caspase-3 precursor and active subunits was downregulated by CHBP in reperfused kidneys. However, HSP70 was upregulated in the post-CS and postreperfused kidneys treated with CHBP. Conclusions Cyclic helix B peptide administered into preservation and reperfusion solutions ameliorated renal ischemia-reperfusion injury, which might be associated with decreased apoptosis, inflammation and caspase-3, but increased HSP70. This novel preservation approach using CHBP may be applied in a porcine kidney transplant model and potential human donor kidney preservation.