Belon Alessandro Rodrigo, Tannuri Ana Cristina Aoun, de Albuquerque Rangel Moreira Daniel, Figueiredo Jose Luiz, da Silva Alessandra Matheus, Serafini Suellen, Guimarães Raimundo Renato, Faria Caroline Silverio, de Alexandre Alcione Sanches, Gonçalves Josiane Oliveira, Paes Vitor Ribeiro, Tannuri Uenis
aLaboratory of Experimental Surgery (LIM26), Department of Surgery, University of Sao Paulo Medical School, Sao Paulo, Brazil.
bPediatric Surgery Division, Pediatric Liver Transplantation Unit and Laboratory of Research in Pediatric Surgery (LIM 30), University of Sao Paulo Medical School, Sao Paulo, Brazil.
J Invest Surg. 2022 Apr;35(4):900-909. doi: 10.1080/08941939.2021.1933274. Epub 2021 Jun 28.
Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury.
To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model.
Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR).
There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group.
DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.
缺血预处理（IPC），无论是直接缺血预处理（DIPC）还是远程缺血预处理（RIPC），都是一种旨在减轻缺血再灌注（I/R）损伤有害影响的程序。
在猪肝移植模型中评估DIPC、RIPC以及两者联合应用的局部和全身效应。
24头猪接受原位肝移植，并分为4组：对照组、供体直接预处理组、受体间接预处理组以及供体直接与受体间接联合预处理组。记录的参数包括：供体和受体体重、移植物与受体体重比（GRWR）、手术时间、热缺血和冷缺血时间以及术中血流动力学值。在切除自体肝脏前（BL）以及再灌注后0小时、1小时、3小时、6小时、12小时、18小时和24小时采集血样进行生化检测：天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、γ-谷氨酰转移酶（GGT）、肌酐、血尿素氮（BUN）、乳酸、总胆红素和直接胆红素。对肝脏、肠道、肾脏和肺组织切片进行组织病理学检查，并使用实时聚合酶链反应（RT-PCR）对与凋亡相关的BAX（促凋亡）和Bcl-XL（抗凋亡）基因、内皮型一氧化氮合酶（eNOS）基因以及与炎症性缺血再灌注损伤相关的IL-6基因的表达进行分子分析。
各组之间在生化和组织病理学参数方面无差异。我们发现与对照组相比，接受IPC的动物肝脏中BAX基因与Bcl-XL的表达比值降低。
DIPC、RIPC或两者联合应用在分子水平产生有益作用，而无生化或组织学改变。
