Glanemann M, Schirmeier A, Lippert S, Langrehr J M, Neuhaus P, Nussler A K
Department of General, Visceral, and Transplantation Surgery, Charité, Campus Virchow Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Transplant Proc. 2005 Sep;37(7):3223-5. doi: 10.1016/j.transproceed.2005.07.002.
Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.
钴原卟啉（CoPP）依赖的血红素加氧酶（HO）-1的诱导已被证明可预防缺血再灌注损伤，而缺血再灌注损伤仍是肝移植后移植物丢失的主要原因。HO-1对肝再生的影响，尤其是在小体积移植物中的影响，尚未得到评估。我们使用一个实验模型，研究了CoPP处理对部分（70%）肝切除术后缺血性损伤肝脏术后恢复的HO-1诱导作用。Wistar大鼠在临时入流阻断（30分钟）下接受部分肝切除术。一组动物在手术前24小时接受CoPP（5mg/kg体重腹腔注射）以在手术时诱导高水平的HO-1，第二组作为未处理的对照。在术后第1、4、7和10天，动物放血处死，血液和肝脏样本保存用于酶学（血清AST和ALT水平）和组织学（有丝分裂指数）分析（每天n = 5）。此外，测量术后体重和残余肝脏的重量。尽管两组之间血清AST和ALT水平以及残余肝脏重量相当，但CoPP处理的动物术后体重表明其从手术中恢复得更快。此外，与未处理的动物相比，该组在第1天有丝分裂细胞的数量显著增加（每2000个肝细胞中分别为33±5和20±5）。术前给予CoPP后HO-1过表达改善了部分肝切除术后缺血性损伤肝脏的肝再生。因此，可以想象，HO-1过表达预防缺血再灌注损伤可能对小体积肝移植物也有益，而不影响其增殖能力。
