Yamanaka Kenya, Houben Philipp, Bruns Helge, Schultze Daniel, Hatano Etsuro, Schemmer Peter
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
PLoS One. 2015 Apr 28;10(4):e0122214. doi: 10.1371/journal.pone.0122214. eCollection 2014.
Although animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine.
A search was performed using the PubMed database to identify agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II - Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel's Random effects model.
The categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the meta-analysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent.
With regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.
尽管动物研究模型常用于减轻肝移植（LT）中的缺血再灌注损伤（IRI），但许多药物尚未成为临床常规用药。
使用PubMed数据库进行检索以确定相关药物，从中选择了58篇包含2700例大鼠肝移植手术的文章。所确定的药物分为以下几类：I - 腺苷激动剂、一氧化氮激动剂、内皮素拮抗剂和前列腺素，II - 枯否细胞灭活剂，III - 补体抑制剂，IV - 抗氧化剂，V - 中性粒细胞灭活剂，VI - 抗凋亡剂，VII - 热休克蛋白和核因子κB诱导剂，VIII - 代谢剂，IX - 中药，以及X - 其他。还使用Mantel-Haenszel随机效应模型对7天生存率进行了荟萃分析。
分类显示，II组（70%）和VII组（71%）的药物在供体治疗实验中的比例最高，而V组的药物在受体治疗实验中的比例更高（83%）。此外，II组药物的90%实验提供了7天生存益处。荟萃分析的风险比（RR）为2.43 [95% CI：1.88 - 3.14]，异质性中等。然而，每项研究的RR过于依赖模型，无法用于寻找最有前景的药物。
关于肝脏IRI病理学，对相关药物进行分类将是设计合适的多因素和多效性方法以制定药理学策略的第一步。
