Lai I-Rue, Chang King-Jen, Chen Chau-Fong, Tsai Hsiu-Wen
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Transplantation. 2006 May 15;81(9):1311-7. doi: 10.1097/01.tp.0000203555.14546.63.
We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats.
The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured.
HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7+/-167.4 U L) when compared with controls (1297.7+/-729.3 U L) and RP+ ZnPP pretreated groups (1429.9+/-750.9 U L). The heme oxygenase activity in treated rats also correlated these results (286.8+/-34.3 pmol mg protein hr for the RP group, 156.3+/-27.5 pmol mg protein hr for the RP+ ZnPP pretreated group, and 170.6+/-19.4 pmol mg protein hr for the control group, 144.8+/-7.8 pmol mg protein hr for the control+ ZnPP pretreated group).
Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.
我们已经报道了血红素加氧酶-1（HO-1）在缺氧预处理机制中的保护作用。我们希望研究HO-1在大鼠肝脏缺血/再灌注（I/R）损伤的远程预处理（RP）中的作用。
通过对大鼠后肢进行四个周期的10分钟缺血-再灌注来产生远程预处理。左叶产生部分肝脏缺血45分钟，随后再灌注240分钟。在不同组的RP大鼠中，在缺血-再灌注损伤前1小时腹腔注射锌原卟啉IX（ZnPP），一种HO酶活性的特异性抑制剂。测量血清丙氨酸转氨酶（ALT）水平、肝脏HO-1蛋白和mRNA的表达、免疫组织化学染色以及HO酶活性。
在RP刺激后4小时，大鼠肝脏中诱导了HO-1，并且这种过表达持续24小时。免疫组织化学染色显示肝细胞中HO-1的诱导。RP后外周淋巴细胞不表达HO-1。与对照组（1297.7±729.3 U/L）和RP+ZnPP预处理组（1429.9±750.9 U/L）相比，RP减轻了I/R损伤后4小时血清ALT水平的升高（283.7±167.4 U/L）。处理大鼠中的血红素加氧酶活性也与这些结果相关（RP组为286.8±34.3 pmol/mg蛋白/小时，RP+ZnPP预处理组为156.3±27.5 pmol/mg蛋白/小时，对照组为170.6±19.4 pmol/mg蛋白/小时，对照+ZnPP预处理组为144.8±7.8 pmol/mg蛋白/小时）。
我们的结果表明，远程预处理中HO-1的诱导对肝脏I/R损伤起到了保护作用。
