Subnormothermic Perfusion with H(2)S Donor AP39 Improves DCD Porcine Renal Graft Outcomes in an Ex Vivo Model of Kidney Preservation and Reperfusion.
Subnormothermic Perfusion with H(2)S Donor AP39 Improves DCD Porcine Renal Graft Outcomes in an Ex Vivo Model of Kidney Preservation and Reperfusion.
复制标题
DOI：
10.3390/biom11030446
复制
发表时间：
2021-03-17
期刊：
影响因子：
5.5
通讯作者：
Sener A
中科院分区：
文献类型：
--
作者：
Juriasingani S;Ruthirakanthan A;Richard-Mohamed M;Akbari M;Aquil S;Patel S;Al-Ogaili R;Whiteman M;Luke P;Sener A
冷保存是移植肾的标准护理。然而，对替代方案的研究，如更高温度的灌流和添加硫化氢(H2S)保存液，已经获得了势头。在这项研究中，我们调查了在21摄氏度的亚常温灌流过程中，将硫化氢供体AP39添加到猪血中是否可以改善移植肾的结果。夹闭肾蒂30min后切取肾脏，冰冻静态冷藏(SCS)4h或21℃低温体外灌流(SNT)或AP39(SNTAP)处理。用自体血在37℃下体外灌流肾脏4h，分别以尿量、组织病理学和RNAseq评价移植肾的功能、损伤和基因表达谱。在保存和再灌流期间，SNTAP组的尿量显著高于其他组，而与SCS组相比，SNTAP组的细胞凋亡损伤显著减少。与SCS(促凋亡基因下调)和SNT(缺氧反应基因下调)组相比，SNTAP组也表现出不同的促生存基因表达模式。21°C亚常温灌流补充硫化氢的血液可改善移植肾的预后。需要进一步的研究来促进这一方法的临床翻译。
Cold preservation is the standard of care for renal grafts. However, research on alternatives like perfusion at higher temperatures and supplementing preservation solutions with hydrogen sulfide (H2S) has gained momentum. In this study, we investigated whether adding H2S donor AP39 to porcine blood during subnormothermic perfusion at 21 °C improves renal graft outcomes. Porcine kidneys were nephrectomized after 30 min of clamping the renal pedicles and treated to 4 h of static cold storage (SCS) on ice or ex vivo subnormothermic perfusion at 21 °C with autologous blood alone (SNT) or with AP39 (SNTAP). All kidneys were reperfused ex vivo with autologous blood at 37 °C for 4 h. Urine output, histopathology and RNAseq were used to evaluate the renal graft function, injury and gene expression profiles, respectively. The SNTAP group exhibited significantly higher urine output than other groups during preservation and reperfusion, along with significantly lower apoptotic injury compared to the SCS group. The SNTAP group also exhibited differential pro-survival gene expression patterns compared to the SCS (downregulation of pro-apoptotic genes) and SNT (downregulation of hypoxia response genes) groups. Subnormothermic perfusion at 21 °C with H2S-supplemented blood improves renal graft outcomes. Further research is needed to facilitate the clinical translation of this approach.
登录
查看更多内容
影响因子：
4.5
作者：
Dion, Marie S.;McGregor, Thomas B.;Sener, Alp
通讯作者：
Sener, Alp
DOI：
10.1097/shk.0000000000000478
发表时间：
2016-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Ahmad A;Olah G;Szczesny B;Wood ME;Whiteman M;Szabo C
通讯作者：
Szabo C
影响因子：
--
作者：
Le Trionnaire, Sophie;Perry, Alexis;Whiteman, Matthew
通讯作者：
Whiteman, Matthew
影响因子：
6.2
作者：
Hosgood, Sarah A.;Nicholson, Michael L.
通讯作者：
Nicholson, Michael L.
影响因子：
6
作者：
Bhattacharjee, Rabindra N.;Ruthirakanthan, Aushanth;Luke, Patrick P. W.
通讯作者：
Luke, Patrick P. W.