Nishizawa H, Egawa H, Inomata Y, Uemoto S, Asonuma K, Kiuchi T, Yamaoka Y, Tanaka K
Department of Transplantation Immunology, Kyoto University Graduate School of Medicine, Kyoto, 606-01, Japan.
J Surg Res. 1997 Oct;72(2):170-6. doi: 10.1006/jsre.1997.5169.
Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.
供体预处理是器官保存中的一个新概念。据报道,己酮可可碱(PTX)可抑制库普弗细胞的激活,并减少大鼠肝移植后肝移植物的损伤。我们使用大鼠肝移植模型评估了PTX预处理供体对冷缺血(CI)或热缺血(WI)后肝损伤的效果。剂量依赖性:每只大鼠腹腔注射PTX(30、50或80mg/kg)或生理盐水。1小时后,夹闭门静脉(PV)和肝动脉(HA)30分钟。移植:在剖腹手术前1小时,给供体大鼠腹腔注射50mg/kg PTX或生理盐水。动物分为两组。在CI组中,移植物在4℃的威斯康星大学溶液中保存12小时后进行移植。在WI组中,供体的PV和HA在供体手术前夹闭30分钟,然后进行移植物移植。在PV再灌注后30分钟、3小时和24小时测量血清肿瘤坏死因子-α(TNF-α)、谷胱甘肽S-转移酶-α(GST-α)和天冬氨酸转氨酶(AST)水平。与对照组相比,PTX预处理组在CI和WI后30分钟时TNF-α、GST-α和AST的血清水平显著降低,在WI组中24小时时进一步受到抑制。这些结果表明,供体PTX预处理对抑制CI和WI后的肝损伤有效。