Apoptosis and regeneration of sinusoidal endothelial cells after extended cold preservation and transplantation of rat liver
Apoptosis and regeneration of sinusoidal endothelial cells after extended cold preservation and transplantation of rat liver
复制标题
大鼠肝脏长期冷藏和移植后肝窦内皮细胞的凋亡与再生
DOI：
10.1097/01.tp.0000290188.38041.f1
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发表时间：
2007-12-15
期刊：
影响因子：
6.2
通讯作者：
Dong, Jiahong
中科院分区：
文献类型：
--
作者：
Zhu, Jin;Wang, Shuguang;Dong, Jiahong
背景窦状隙内皮细胞（SEC）对冷缺血再灌注（I/R）损伤特别敏感。我们研究了冷保存肝移植后移植物的损伤和恢复过程，特别关注SEC的增殖和相关的调节机制。方法。雄性SD大鼠按移植物在威斯康星州大学[UW]溶液中冷保存时间长短分为UW 1h组和UW 12 h组。观察原位肝移植术后移植物功能、细胞凋亡率、SECs增殖情况及相关调控因子的表达。与肝细胞相比，SEC对冷I/R损伤诱导的凋亡更敏感。用溴脱氧尿苷和大鼠内皮细胞抗原- I双标免疫组化法检测，与肝细胞相比，SEC的增殖延迟，分别在UW 1h组72 h和UW 12 h组96 h达到高峰。血管内皮生长因子在再灌注后24小时增加，在两组中在72小时达到峰值。Flt-1和flk-1的表达主要局限于SEC，表达高峰出现在72 ~ 96 h之间，这与UW 1h组SEC增殖的高峰相一致。与假手术组相比，UW 12 h组flt-1在实验过程中的任何时间点均显著降低。延长冷保存和移植后大鼠肝脏的延迟恢复与SEC的延迟再生相关，这是由于细胞凋亡增加和flt-1表达减少。这些结果表明，SECs在冷保存肝移植中起着重要作用。
Background. Sinusoidal endothelial cells (SECs) are particularly susceptible to cold ischemia-reperfusion (I/R) injury. We have examined the process of injury and recovery of graft after cold-preserved liver transplantation, with special focus on the proliferation of SECs and regulatory mechanisms involved.Methods. Male SD rats were divided into two groups according to length of cold preservation time in University of Wisconsin [UW] solution of graft: UW1h group and UW12h group. Graft function, incidence of apoptosis, proliferation of SECs and the expression of related regulatory factors were assessed after orthotopic liver transplantation (OLT).Results. SECs are more sensitive to apoptosis induced by cold I/R injury compared with hepatocytes. Using bromodeoxyuridine and rat endothelial cell antigen- I double immunostaining assay, SECs exhibited a delayed proliferation in comparison with hepatocytes, reaching a peak at 72 hr in UW1h group and 96 hr in UW12h group, respectively. Vascular endothelial growth factor increased at 24 hr after reperfusion, and peaked at 72 hr in both groups. Flt-1 and flk-1 expression was found to be mainly limited to SECs, with a peak in expression occurring between 72 and 96 hr, which coincided with the peak in SEC proliferation in UW1h group. However, flt-1 was found to be reduced significantly at any time throughout the experiments in UW12h group compared to sham.Conclusion. The delayed recovery of rat liver after extended cold preservation and transplantation correlates with a retarded regeneration of SECs due to increased apoptosis and reduced expression of flt-1. These results suggest that SECs play an important role in cold-preserved liver transplantation.