Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pathobiology. 2010;77(3):136-46. doi: 10.1159/000292647. Epub 2010 May 28.
Ischemic preconditioning (IPC) has been gradually introduced into clinical liver surgery and transplantation in recent years. However, the protective effects of IPC on hepatic warm ischemia/reperfusion (I/R) injury and the potential mechanisms involved are not fully understood. We aimed to evaluate whether the reduction of apoptotic sinusoidal endothelial cells (SECs), induced by IPC, contributes to its protective effect.
Male Wistar rats were randomized into three experimental groups: the continuous clamping group underwent 60 min of 70% hepatic ischemia; the IPC group received 10 min ischemia followed by 10 min reperfusion prior to ischemia, and the sham control (sham) underwent a sham operation without ischemia. Hepatocyte and SEC apoptosis, liver necrotic areas and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid, tumor necrosis factor, myeloperoxidase (MPO) and malondialdehyde were determined. Expression of cysteine-aspartic acid protease-3 (caspase-3) in hepatocytes and SECs was also investigated. Furthermore, the hepatic leukocyte infiltration was assessed by intravital fluorescence microscopy.
IPC exhibited a significant alleviation of their postischemic liver function. Serum AST, ALT and tissue MPO were significantly decreased by IPC, and the degree of hepatocyte and SEC apoptosis was significantly inhibited, as shown by the decreased numbers of adherent leukocytes.
IPC attenuates hepatic I/R injury by the reduction of leukocyte infiltration, the reduction hepatic enzymatic leakage and the depression of apoptotic cells. SECs are more sensitive to apoptosis induced by warm I/R injury compared to hepatocytes.
缺血预处理（IPC）近年来逐渐被引入临床肝外科和肝移植领域。然而，IPC 对肝热缺血/再灌注（I/R）损伤的保护作用及其潜在机制尚不完全清楚。我们旨在评估 IPC 诱导的凋亡性窦内皮细胞（SEC）减少是否有助于其保护作用。
雄性 Wistar 大鼠随机分为三组实验：连续夹闭组进行 60 分钟 70%肝缺血；IPC 组在缺血前进行 10 分钟缺血和 10 分钟再灌注；假手术（sham）组进行假手术而不进行缺血。检测肝细胞和 SEC 凋亡、肝坏死面积以及丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、透明质酸、肿瘤坏死因子、髓过氧化物酶（MPO）和丙二醛水平。还研究了肝细胞和 SEC 中半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的表达。此外，通过活体荧光显微镜评估肝白细胞浸润。
IPC 显著减轻了缺血后肝脏的功能障碍。IPC 显著降低了血清 AST、ALT 和组织 MPO，显著抑制了肝细胞和 SEC 凋亡，附着的白细胞数量减少。
IPC 通过减少白细胞浸润、降低肝酶漏出和抑制凋亡细胞来减轻肝 I/R 损伤。与肝细胞相比，SEC 对热 I/R 损伤诱导的凋亡更为敏感。
