HO-1诱导剂体外灌注对大鼠移植肝脏保护作用的研究

Protection of liver grafts with HO-1 inducer by extra-corporeal liver perfusion in rats

目的探讨在移植肝脏低温保存期间灌注血红素加氧酶-1(heme oxygenase-1,HO-1)诱导剂钴原卟啉(cobalt protoporphyrin,CoPP)对大鼠移植肝脏的保护作用。方法以Wistar大鼠为供体,SD大鼠为受体,根据供肝体外灌注低温保存期间所灌注的液体不同,将其分为4组:空白对照组、CoPP组、nodosin组和锌原卟啉(zinc protoporphyrin,ZnPP)组。每组各建立12对大鼠原位肝移植模型,各组分别在移植手术后1 d、3 d、7 d、21 d处死3只大鼠切取肝脏组织标本,进行肝脏组织病理检查与Suzuki评分。结果原位肝移植术后1 d、3 d、7 d,CoPP组和nodosin组大鼠的肝脏病理损伤比空白对照组和ZnPP组轻,但Suzuki评分差异无统计学意义(P>0.05)。原位肝移植术后21 d,nodosin组与CoPP组的病理损伤均较空白对照组轻,两组的Suzuki评分与空白对照组比较差异有统计学意义(P<0.01,P<0.05)。ZnPP组的移植肝脏损伤较重,ZnPP组的Suzuki评分与nodosin组比较差异有统计学意义(P<0.01)。结论在移植肝低温保存期间灌注HO-1诱导剂可以减轻大鼠肝移植术后肝脏组织的病理损伤,而且在术后晚期对移植肝保护效果更加明显。

Objective To investigate the protective effect on liver grafts by extra-corporeal liver perfusion with heine oxygenase-1 （ HO-1 ） inducer cobalt protoporphyrin （CoPP） during hypothermie storage on rat orthotopic liver transplantation model. Methods Liver grafts were taken from Wistar rats and transplanted to SD rats. Extra-corporeal liver perfusions of liver grafts were performed during hypothermic storage with different solution before OLT. The rats were divided into control group, CoPP group, nodosin （which is effective component in Isodon Serra） group and ZnPP （which is HO-1 inhibitor ） group with twelve pairs of rats in each group. The rat grafts were perfused with lactated Ringer＇s solution, 125 μg/ml CoPP, 200 μg/ml nodosin and 500 μg/ml ZnPP respectively before OLT. On day 1, Day 3, Day 7 and Day 21 after OLT, three recipient rats in each group were killed and liver specimens were collected. HE staining pathological examination and Suzuki score were performed. Results On day 1, Day 3 and Day 7 after OLT, the pathological damage of liver in CoPP group and nodosin group were slighter compared with the control group and ZnPP group, but the Suzuki score of each group showed no statistically significance （P 〉 0. 05 ）. On day 21 after OLT, the pathological damage of liver in CoPP group and nodosin group were slighter than that in control group, and there was statistically significant difference in the Suzuki score between every two groups （P 〈0. 05 and P 〈0. 01, respectively）. The pathological damage of liver in ZnPP group was severe, and there was statistically significant difference in the Suzuki score between nodosin group and ZnPP group （ P 〈 0. 01 ）. Conclusions Extra-corporeal liver perfusion with HO-1 inducer during hypothermic storage can reduce the pathological damage of liver after OLT in rats, and the protective effect on liver grafts was better in the later period after OLT.