Lai I-Rue, Ma Ming-Chieh, Chen Chau-Fong, Chang King-Jen
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Transplantation. 2004 Apr 15;77(7):1004-8. doi: 10.1097/01.tp.0000121507.84801.36.
Hypoxic preconditioning (HP) confers cytoprotection against ischemia/reperfusion (I/R) injury. This effect is in part attributable to the induction of heme oxygenase (HO)-1. This experiment evaluates liver cell damage after I/R injury in HP rats.
HP rats were prepared by exposure (15 hr/day) to an altitude chamber (5500 m) for 2 weeks. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 180 min of reperfusion. Zinc (Zn) protoporphyrin (PP), a specific inhibitor of HO enzymatic activity, was subcutaneously injected 1 hr before the I/R injury into separate groups of sea-level (SL) control and HP rats. Serum alanine aminotransferase (ALT) levels, liver HO-1 mRNA and protein, and HO enzymatic activity were measured.
HO-1 was induced in the livers of rats exposed to HP. The levels of HO-1 mRNA and protein were obviously overexpressed after 2 weeks of HP. HP diminished the elevation of serum ALT levels after I/R injury (83.7+/- 4.9 U/L) when compared with SL controls (280.8+/-19.4 U/L) and HP+ZnPP-pretreated groups (151.3+/-4.4 U/L). The HO activity in treated rats also was correlated with these results (237.9+/-19.8 pmol/mg of protein per hour for the HP group, 164.3+/-12.7 pmol/mg of protein per hour for the HP+ZnPP group, and 182.6+/-8 pmol/mg of protein per hour for the SL controls).
The authors' results indicated that the induction of HO-1 in hypoxic preconditioning played a protective role against hepatic I/R injury.
低氧预处理（HP）可赋予细胞对缺血/再灌注（I/R）损伤的保护作用。这种效应部分归因于血红素加氧酶（HO）-1的诱导。本实验评估HP大鼠I/R损伤后的肝细胞损伤情况。
通过将大鼠置于海拔舱（5500米）中每天暴露15小时，持续2周来制备HP大鼠。左叶产生部分肝缺血45分钟，随后再灌注180分钟。在I/R损伤前1小时，将HO酶活性的特异性抑制剂锌（Zn）原卟啉（PP）皮下注射到不同组的海平面（SL）对照大鼠和HP大鼠中。测量血清丙氨酸氨基转移酶（ALT）水平、肝脏HO-1 mRNA和蛋白以及HO酶活性。
暴露于HP的大鼠肝脏中诱导了HO-1。HP 2周后，HO-1 mRNA和蛋白水平明显过度表达。与SL对照（280.8±19.4 U/L）和HP + ZnPP预处理组（151.3±4.4 U/L）相比，HP减轻了I/R损伤后血清ALT水平的升高（83.7±4.9 U/L）。处理后大鼠的HO活性也与这些结果相关（HP组为237.9±19.8 pmol/mg蛋白/小时，HP + ZnPP组为164.3±12.7 pmol/mg蛋白/小时，SL对照组为182.6±8 pmol/mg蛋白/小时）。
作者的结果表明，低氧预处理中HO-1的诱导对肝脏I/R损伤起到了保护作用。
