Department of Hepatobiliary & Pancreatic Surgery, The First Norman Bethune Hospital Affiliated to Jilin University, Changchun, 130021 Jilin Province, China.
Department of Hepatobiliary & Pancreatic Surgery, Third Hospital, China-Japan Union Hospital of Jilin University, Changchun, 130033 Jilin Province, China.
Life Sci. 2016 Apr 1;150:76-80. doi: 10.1016/j.lfs.2016.02.077. Epub 2016 Feb 24.
Our objective was to compare the protective efficacy of ischemic preconditioning (IPC) and remote ischemic preconditioning (RIPC) against liver ischemia/reperfusion injury (IRI) and to evaluate their combined protective effect in mouse liver transplantation (MLT).
Mice were randomly allocated to sham, IPC, RIPC, or IPC+RIPC groups. The animals were sacrificed at 2h, 24h, and 3 days after reperfusion. Blood samples were collected to evaluate alanine aminotransferase, TNF-α, and innate immune response. Liver tissue samples were obtained for histological evaluation, terminal deoxynucleotidyltransferased UTP nick end labeling, malondialdehyde (MDA) assay.
Mice given preconditioning measures had significantly lower increase in transaminase, TNF-α expression, MDA formation, liver injury scores, and apoptosis index at 2h, 24h and 3 days after liver transplantation. The percentages of CD11b(+), CD11b(+)CD16/32(+) and CD11b(+) CD16/32(high) in white blood cells at 3 days after MLT were significantly lower than in the sham group. The results of factorial analysis demonstrated no synergistic effect for IPC and RIPC, except for MDA formation 2h after reperfusion (p=0.038).
Based on the synergistic and addictive effect on liver IRI induced by MLT between IPC and RIPC, the study suggested ways in which combined preconditionings could be elicited in patients undergoing planned procedures complicated by IRI to support better outcomes.
本研究旨在比较缺血预处理（IPC）和远程缺血预处理（RIPC）对肝缺血/再灌注损伤（IRI）的保护作用，并评估其在小鼠肝移植（MLT）中的联合保护作用。
将小鼠随机分为假手术组、IPC 组、RIPC 组和 IPC+RIPC 组。在再灌注后 2h、24h 和 3 天处死动物。采集血样评估丙氨酸转氨酶、TNF-α和固有免疫反应。采集肝组织样本进行组织学评估、末端脱氧核苷酸转移酶 UTP 缺口末端标记法、丙二醛（MDA）测定。
预处理组小鼠在肝移植后 2h、24h 和 3 天，转氨酶升高、TNF-α表达、MDA 形成、肝损伤评分和凋亡指数均显著降低。在 MLT 后 3 天，白细胞中 CD11b(+)、CD11b(+)CD16/32(+)和 CD11b(+)CD16/32(high)的百分比明显低于假手术组。析因分析结果表明，IPC 和 RIPC 之间除再灌注后 2h 的 MDA 形成外（p=0.038），没有协同作用。
基于 IPC 和 RIPC 对 MLT 诱导的肝 IRI 的协同和累加作用，本研究提示了在计划接受可能发生 IRI 的复杂手术的患者中诱发联合预处理的方法，以支持更好的结果。
