钙蛋白酶与肝移植缺血再灌注损伤关系的实验研究

目的 探讨大鼠肝在不同冷缺血期、复温期及再灌注期钙蛋白酶活性变化，以及钙蛋白酶抑制剂对离体灌注肝功能及原位肝移植大鼠生存的影响。方法 SD大鼠。共5个实验部分：（1）冷缺血实验；（2）冷缺血后复温实验；（3）冷缺血后再灌注实验；（4）钙蛋白酶抑制剂实验；（5）原位肝移植实验。结果 冷缺血12h始，肝组织中钙蛋白酶活力明显增加，并随着冷缺血时间的延长而逐渐明显增加（P＜0.01）。冷缺血复温30min始，肝组织中钙蛋白酶活力明显增加，并随着复温时间延长而逐渐明显增加（P＜0.01）。肝组织冷缺血0和12h再灌注60min钙蛋白酶明显增加（P＜0.05）。钙蛋白酶抑制剂明显增加（P＜0.05）。而冷缺血24h再灌注30min钙蛋白酶便明显增加（P＜0.05）。钙蛋白酶抑制剂可明显地降低离体灌注肝AST水平及增加胆汁量（分别P＜0.01）。结论 肝移植冷缺血期、复温期及再灌注期钙蛋白酶均明显增高，钙蛋白酶抑制剂可明显地改善移植肝功能。

An experimental study on relationship between calpain and liver graft ischemia reperfusion injury

Objective To investigate the changes of hepatic cell calpain activity during different periods of cold ischemia (CI), rewarming, reperfusion and the effects of calpain inhibitor on both the liver function of isolated perfused rat liver (IPRL) and the survival rate of rats with orthotopic liver transplantation (OLT). Methods SD were randomized into: (1) CI group (n=6), (2) Rewarming group after different periods of CI (n=30), (3) Reperfusion group after different periods of CI (n=20), (4) Calpain inhibitor group (n=12) and (5) OLT group (n=20). Results Calpain activity gradually increased with prolongation of CI time (P<0 01). In 30 min after the rewarming, the activity of calpain began to significantly increase (P<0 01). In 0 and 12 h after ischemia, reperfusion for 60 min resulted in significant increase of calpain (P<0 05). In 24 h after ischemia, reperfusion for only 30 min resulted in significance of calpain (P<0 05). Calpain inhibitor remarkably decreased AST release and increased bile production in the IPRL (P<0 01). Conclusions The increase of calpain activation occurs in each phase of CI, rewarming and reperfusion during liver transplantation. Calpain inhibitor can markedly improves the liver graft function.