Transient limb ischemia induces remote preconditioning in liver among rats: The protective role of heme oxygenase-1
Transient limb ischemia induces remote preconditioning in liver among rats: The protective role of heme oxygenase-1
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DOI：
10.1097/01.tp.0000203555.14546.63
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发表时间：
2006-05-15
期刊：
影响因子：
6.2
通讯作者：
Tsai, Hsiu-Wen
中科院分区：
文献类型：
--
作者：
Lai, I-Rue;Chang, King-Jen;Tsai, Hsiu-Wen
背景。我们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。我们希望探讨HO-1在大鼠肝缺血再灌注（I/R）损伤的远程预处理（RP）中的作用。远距离预处理采用大鼠后肢缺血再灌注4个周期，每次10min。左肝局部缺血45分钟，再灌注240分钟。在RP大鼠缺血再灌注损伤前1小时腹腔注射特异性HO酶活性抑制剂锌原卟啉IX （ZnPP）。测定血清丙氨酸转氨酶（ALT）水平、肝脏HO-1蛋白和mRNA表达、免疫组化染色及HO酶活性。在RP刺激后4小时，HO-1在大鼠肝脏中被诱导，并持续过表达24小时。免疫组化染色显示肝细胞中HO-1的诱导。RP后外周血淋巴细胞不表达HO-1。与对照组（1297.7 +/- 729.3 UL-1）和RP+ ZnPP预处理组（1429.9 +/- 750.9 UL-1）相比，RP降低I/R损伤后4小时血清ALT水平升高（283.7 +/- 167.4 UL-1）。处理大鼠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（-1）蛋白hr(-1)， RP+ ZnPP预处理组为156.3 +/- 27.5 pmol mg（-1）蛋白hr(-1)，对照组为170.6 +/- 19.4 pmol mg（-1）蛋白hr（-1)，对照组+ ZnPP预处理组为144.8 +/- 7.8 pmol mg（-1）蛋白hr(-1)）。我们的研究结果表明，在远程预处理中诱导HO-1对肝I/R损伤具有保护作用。
Background. 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.Methods. 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.Results. 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 UL-1) when compared with controls (1297.7 +/- 729.3 UL-1) and RP+ ZnPP pretreated groups (1429.9 +/- 750.9 UL-1). The heme oxygenase activity in treated rats also correlated these results (286.8 +/- 34.3 pmol mg(-1) protein hr(-1) for the RP group, 156.3 +/- 27.5 pmol mg(-1) protein hr(-1) for the RP+ ZnPP pretreated group, and 170.6 +/- 19.4 pmol mg(-1) protein hr(-1) for the control group, 144.8 +/- 7.8 pmol mg(-1) protein hr(-1) for the control + ZnPP pretreated group).Conclusion. Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.