Chávez-Cartaya R E, DeSola G P, Wright L, Jamieson N V, White D J
Department of Surgery, Addenbrookes Hospital, University of Cambridge Clinical School, United Kingdom.
Transplantation. 1995 Apr 15;59(7):1047-52. doi: 10.1097/00007890-199504150-00023.
The complement cascade was inactivated in a model of rat liver ischemia with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor type 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v. over 24 hr after vascular occlusion. Sham-operated rats, nontreated rats submitted to liver ischemia, and rats pretreated with cobra venom factor and submitted to liver ischemia were used as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobes of the liver for 45 min, followed by a 24-hr period of follow-up after reperfusion. Liver blood flow and hemoglobin saturation were recorded for 1 hr after declamping, with statistically significant differences between the experimental groups and the untreated control group, which received liver ischemia (P < 0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to ischemia (P < 0.01). Alanine aminotransferase levels were also significantly lower in the sCR1-treated rats at 6 and 24 hr (P < 0.05). Complement activity was reduced to 25% and 12.5% of normal rats with the respective doses of sCR1. Immunoperoxidase stainings for C3 and C9 were performed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom factor or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.
在大鼠肝脏缺血模型中使补体级联失活，目的是研究补体在缺血再灌注后组织损伤中的作用。在血管闭塞后24小时内，以25mg/kg的单剂量或2剂50mg/kg的静脉注射方式给予可溶性人补体受体1型（sCR1）。假手术大鼠、未处理的肝脏缺血大鼠以及用眼镜蛇毒因子预处理并进行肝脏缺血的大鼠用作对照。该实验包括暂时中断流向肝脏左外侧叶和内侧叶的动脉和门静脉血流45分钟，然后在再灌注后进行24小时的随访。松开夹闭后1小时记录肝脏血流和血红蛋白饱和度，实验组与接受肝脏缺血的未处理对照组之间存在统计学显著差异（P<0.001）。在24小时时，测定半乳糖消除作为肝功能测试；与接受缺血的对照大鼠相比，sCR1处理的大鼠明显更好（P<0.01）。在6小时和24小时时，sCR1处理的大鼠丙氨酸转氨酶水平也显著更低（P<0.05）。使用相应剂量的sCR1，补体活性分别降至正常大鼠的25%和12.5%。对肝脏切片进行C3和C9的免疫过氧化物酶染色；在接受缺血的对照组中显示有C3和C9的内皮沉积。在sCR1（25mg/kg）处理的大鼠中存在少量C3沉积，但在眼镜蛇毒因子或sCR1（50mg/kg）组中不存在。这些结果证实sCR1可使补体失活，并改善大鼠肝脏的再灌注损伤。
