蛋白酶抑制剂对大鼠肝缺血再灌注和原位肝移植后肝功能的保护作用

目的 探讨中性粒细胞及蛋白酶抑制剂在大鼠肝脏缺血再灌注损伤中的作用。方法 建立大鼠热缺血再灌注及原位肝移植模型。检测血清谷丙转氨酶（ＡＬＴ）、乳酸脱氢酶（ＬＤＨ）、肝脏髓过氧化物酶（ＭＰＯ）含量，观察肝脏病理组织学改变，定量计数浸润的中性粒细胞等，热缺血组于缺血前用药，缺血４５ｍｉｎ后再灌注４ｈ取样，移植组于受体术前１ｈ用药，移植４ｈ后取样。结果 对照组ＡＬＴ，ＬＤＨ，ＭＰＯ均较实验组显著升高（Ｐ〈０．０１）。组织学观察肝组织损害较重，中性粒细胞浸润明显，与实验组相比有显著差异（Ｐ〈０．０１）。结论 肝脏冷、热缺血再灌注损伤时中性粒细胞参与并起了重要的作用。而应用蛋白酶掏剂抑肽酶（ＡＰ）可以减轻缺血再灌注损伤的程度。并对肝脏功能有保护作用。

Protective effects of protease inhibitor on liver function after ischemia reperfusion and orthotopic liver transplantation in rats

Objective To investigate the role of neutrophils and protease inhibitor in the pathogenesis of hepatic ischemia reperfusion injury. Methods The models of liver ischemia reperfusion (LIR) and orthotopic liver transplantation (OLT) were established in rats. The contents of serum ALT and LDH and liver myeloperoxidase(MPO) were determined. Meanwhile, the hepatic pathohistological changes were observed and the number of infiltrating neutrophils counted. As for the LIR model, the animals were administered with aprotinin (AP) before ischemia. Then reperfusion was achieved 45 min after ischemia. The samples were collected after reperfusion for 4 h. In OLT model, the animals were administered with AP 1 h before the transplantation and the samples were collected 4 h postoperatively. Results The contents of serum ALT and LDH and liver MPO were significantly higher in the control group than in the experimental one (P<0 01). Furthermore, the liver in the control group showed severe hepatocytic damage and significant neutrophil infiltration. The number of infiltrating neutrophils was remarkably increased as compared with the experimental group (P<0.01). Conclusions Neutrophils play an important role in rat liver ischemia reperfusion injury. Aprotinin, the protease inhibitor, might alleviate the injury and protect the liver function.