Carbon monoxide induces hypothermia tolerance in Kupffer cells and attenuates liver ischemia/reperfusion injury in rats.
Carbon monoxide induces hypothermia tolerance in Kupffer cells and attenuates liver ischemia/reperfusion injury in rats.
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DOI：
10.1002/lt.22415
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发表时间：
2011-12
影响因子：
4.6
通讯作者：
Murase, Noriko
中科院分区：
文献类型：
--
作者：
Lee, Lung-Yi;Kaizu, Takashi;Toyokawa, Hideyoshi;Zhang, Matthew;Ross, Mark;Stolz, Donna B.;Huang, Chao;Gandhi, Chandrashekhar;Geller, David A.;Murase, Noriko
供肝缺血/再灌注(I/R)损伤是影响供肝质量、术后护理和肝移植(LTX)预后的主要问题。枯否细胞(Kupffer cell，KC)在I/R损伤中起重要作用，但对其在冷保存过程中的变化知之甚少。我们检测了血红素降解的细胞保护产物一氧化碳(CO)的预处理是否会影响冷藏期间KC的活性，并保护肝移植免受LTX诱导的I/R损伤。在体外，原代培养的大鼠KC分别用低温(4℃，20%O2)、内毒素或低氧(37℃，5%O2)刺激24小时。大鼠KC在低温条件下可产生ROS，但不产生肿瘤坏死因子-α或NO。KC与CO预先孵育可上调HSP70并抑制ROS的产生。大鼠供肝经250 ppm CO处理24 h后，移植肝在UW液中冷保存18 h后，HSP70表达增加，血清AST/ALT水平降低，肝组织坏死区和炎性细胞浸润明显减少。联合处理组大鼠移植肝组织中肿瘤坏死因子-α、细胞间黏附分子-1和诱导型一氧化氮合酶的表达减少，促凋亡的Bax基因表达减少，caspase-3和PARP表达降低。因此，供体用CO预处理可改善与LTX相关的I/R损伤，肝脏HSP70表达增加，尤其是在KC人群中。
Ischemia/reperfusion (I/R) injury in liver grafts, initiated by cold preservation and augmented by reperfusion, is a major problem complicating graft quality, post-transplant patient care, and outcomes of liver transplantation (LTx). Kupffer cells (KC) play important roles in I/R injury; however, little is known about their changes during cold preservation. We examined whether pretreatment with carbon monoxide (CO), a cytoprotective product of heme degradation, would influence KC activity during cold storage and protect the liver graft against LTx-induced I/R injury. In vitro, primary rat KC were stimulated for 24 hrs with hypothermia (4°C, 20% O2), LPS, or hypoxia (37°C, 5% O2) with and without CO pretreatment. When exposed to hypothermia, rat KC produced ROS, but not TNF-α or NO. Preincubation of KC with CO upregulated HSP70 and inhibited ROS generation. When liver grafts obtained from donor rats exposed to CO (250 ppm) for 24 hrs were transplanted after 18 hrs cold preservation in UW solution, HSP70 expression in the grafts increased, and serum AST/ALT levels as well as necrotic area and inflammatory infiltrates were significantly reduced after LTx, when compared to control grafts. CO-pretreated liver grafts showed less TNF-α, ICAM-1 and iNOS mRNA upregulation, as well as reduced pro-apoptotic Bax mRNA, cleaved caspase-3 and PARP expressions. Thus, donor pretreatment with CO ameliorates I/R injury associated with LTx, with an increased hepatic HSP70 expression, particularly in KC population.
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影响因子：
4.6
作者：
Ikeda, Atsushi;Ueki, Shinya;Nakao, Atsunori;Tomiyama, Koji;Ross, Mark A.;Stolz, Donna B.;Geller, David A.;Murase, Noriko
通讯作者：
Murase, Noriko
影响因子：
13.5
作者：
Huet, PM;Nagaoka, MR;Bilodeau, M
通讯作者：
Bilodeau, M
影响因子：
9.6
作者：
Kume, M;Yamamoto, Y;Yamaoka, Y
通讯作者：
Yamaoka, Y
影响因子：
6.2
作者：
Mueller, THJ;Kienle, K;Rentsch, M
通讯作者：
Rentsch, M
影响因子：
13.5
作者：
Kiemer, AK;Gerbes, AL;Vollmar, AM
通讯作者：
Vollmar, AM