Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes

被引：64

作者：

Degli Esposti D. ^{[1
,2
,3
]}

Sebagh M. ^{[4
]}

Pham P. ^{[1
,2
]}

Reffas M. ^{[1
,2
]}

Poüs C. ^{[3
,5
]}

Brenner C. ^{[6
]}

Azoulay D. ^{[1
,2
]}

Lemoine A. ^{[1
,2
,3
]}

机构：

[1] AP-HP, Hô Pital Paul Brousse, Centre Hé Patobiliaire, Villejuif Cedex 94804

[2] Inserm U1004, Université Paris 11, Institut André Lwoff, Villejuif 94800

[3] Faculté de Pharmacie, Châtenay-Malabry Cedex 92296

[4] Hô Pital Paul Brousse, Service D'Anatomie Pathologique, Université Paris 11, Villejuif Cedex 94804

[5] EA4530, Laboratoire de Biochimie et Biologie Cellulaire, Faculté de Pharmacie, Châ tenay-Malabry Cedex 92296

[6] UMR-S 769 Signalisation et Physiopathologie Cardiaque, Université Paris 11, PRES Universud-Paris, Châtenay-Malabry Cedex 92296

来源：

Cell Death & Disease | 2011年 / 2卷 / 1期

关键词：

Autophagy; Ischemia/reperfusion; Ischemic preconditioning; Liver; Liver transplantation; Steatosis;

D O I：

10.1038/cddis.2010.89

中图分类号：

学科分类号：

摘要：

Whether ischemic preconditioning (IP) reduces ischemia/reperfusion (I/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological and immunohistological characteristics of post-reperfusion biopsies were analyzed. Incidence of post-reperfusion necrosis was increased (10/10 versus 9/14, respectively; P<0.05) and the clinical outcome of recipients was worse for non-IP steatotic liver grafts compared with non-IP non-steatotic grafts. IP significantly lowered the transaminase values only in patients receiving a non-steatotic liver. An increased expression of beclin-1 and LC3, two pro-autophagic proteins, tended to decrease the incidence of necrosis (P=0.067) in IP steatotic livers compared with non-IP steatotic group. IP decreased the incidence of acute and chronic rejection episodes in steatotic livers (2/12 versus 6/10; P=0.07 and 2/12 versus 7/10; P<.05, respectively), but not in non-steatotic livers. Thus, IP may induce autophagy in human steatotic liver grafts and reduce rejection in their recipients. © 2011 Macmillan Publishers Limited.

引用

页码：e111 / e111

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