Liver graft exposure to carbon monoxide during cold storage protects sinusoidal endothelial cells and ameliorates reperfusion injury in rats.
Liver graft exposure to carbon monoxide during cold storage protects sinusoidal endothelial cells and ameliorates reperfusion injury in rats.
复制标题
DOI：
10.1002/lt.21918
复制
发表时间：
2009-11
影响因子：
4.6
通讯作者：
Murase, Noriko
中科院分区：
文献类型：
--
作者：
Ikeda, Atsushi;Ueki, Shinya;Nakao, Atsunori;Tomiyama, Koji;Ross, Mark A.;Stolz, Donna B.;Geller, David A.;Murase, Noriko
肝脏缺血/再灌注（I/R）损伤显著影响肝移植（LTx）后的短期和长期结局。在冷保存期间，引起损伤的关键步骤包括窦状内皮细胞（SEC）的改变。由于一氧化碳（CO）对血管内皮细胞具有强有力的细胞保护作用，本研究探讨了CO处理离体肝移植在冷藏期间是否可以保护SEC并改善肝I/R损伤。将大鼠肝移植于含5%CO的UW液（CO-UW）中保存18-24小时，移植于同系刘易斯大鼠体内。冷保存18小时后，SEC损伤明显，碘化丙啶（PI）核染色SEC，PI+ SEC的频率在CO-UW中存储的移植物比对照UW中显着降低。冷保存过程中CO的SEC保护作用与ICAM易位减少和MMP释放减少有关。冷保存18 h后，CO-UW组血清ALT水平和肝组织坏死明显低于对照组。冷藏24小时，对照组存活率为35%（7/20），CO-UW组存活率为80%（8/10）。CO-UW的这些有益作用与显著减少中性粒细胞外渗、下调肝脏TNF-α和ICAM-1 mRNA以及减少肝脏ERK激活有关。来自枯否细胞耗尽供体或无假菌供体的肝移植物在冷保存期间显示较少的SEC死亡，并且CO-UW进一步减少SEC死亡。在冷保存过程中向切除的肝移植物输送CO有效地改善了SEC损伤和肝I/R损伤。
Hepatic ischemia/reperfusion (I/R) injury significantly influences short and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examines if CO treatment of excised liver grafts during cold storage could protect SEC and ameliorate hepatic I/R injury. Rat liver grafts were preserved in UW solution containing 5% CO (CO-UW) for 18–24 hrs and transplanted into syngenic Lewis rats. After 18 hrs cold preservation, SEC damage was evident with Propidium Iodide (PI) nuclear stain on SEC, and the frequency of PI+ SEC was significantly lower in grafts stored in CO-UW than in control UW. SEC protection with CO associated with decreased ICAM translocation and less MMP release during cold preservation. After LTx with 18 hrs cold preservation, serum ALT levels and hepatic necrosis were significantly less in CO-UW than in control UW group. With 24 hrs cold storage, 35% (7/20) survived with control UW, while the survival with CO-UW improved to 80% (8/10). These beneficial effects of CO-UW associated with significant reduction of neutrophil extravasation, down-regulation of hepatic mRNA for TNF-α and ICAM-1, and less hepatic ERK activation. Liver grafts from Kupffer cell depleted donors or pseudogerm-free donors showed less SEC death during cold preservation, and CO-UW further reduced SEC death. CO delivery to excised liver grafts during cold preservation efficiently ameliorates SEC damage and hepatic I/R injury.
登录
查看更多内容
影响因子：
6.2
作者：
Katori, M;Tamaki, T;Kakita, A
通讯作者：
Kakita, A
DOI：
10.1152/ajpgi.2001.281.4.g957
发表时间：
2001-10-01
影响因子：
4.5
作者：
Rozenfeld, RA;Liu, XL;Hsueh, W
通讯作者：
Hsueh, W
DOI：
10.1152/ajpgi.00144.2007
发表时间：
2008-01-01
影响因子：
4.5
作者：
Kaizu, Takashi;Ikeda, Atsushi;Murase, Noriko
通讯作者：
Murase, Noriko
影响因子：
13.5
作者：
IKEDA, T;YANAGA, K;SUGIMACHI, K
通讯作者：
SUGIMACHI, K
影响因子：
6.2
作者：
ARII, S;MONDEN, K;IMAMURA, M
通讯作者：
IMAMURA, M