PEP-1介导的血红素氧合酶-1在大鼠肝脏缺血／再灌注损伤中的抗凋亡作用

Anti-apoptotic effects of PEP-1-heme oxygenase-1 fusion protein on liver ischemia-reperfusion inju- ry in rats

目的探讨PEP-1介导的血红素氧合酶-1（HO-1）在SD大鼠肝脏缺血／再灌注损伤中的抗凋亡作用。方法按照随机对照原则将30只大鼠分成三组，假手术组（S组）、缺血／再灌注组（IR组）、PEP—WHO-1处理＋缺血／再灌注组（PEP—1组）。在肝缺血40min再灌注6h后，在无菌条件下开腹解剖出肝脏，光镜下明确病理变化；免疫组织化学SP法检测HO-1蛋白表达；TUNEL法和流式细胞仪检测肝细胞凋亡细胞表现及凋亡率；Western blot检测Bcl-2和Caspase-3的表达。结果PEP-1组的肝缺血／再灌注损伤HE病理表现明显较IR组减轻，HO-1蛋白表达和Bcl-2的表达PEP-1组较IR组高，凋亡率和Caspase-3的表达PEP-1组较IR组低，两组差异有统计学意义（P〈0．05）。结论HO-1在供肝缺血／再灌注损伤中是通过多途径发挥抗凋亡保护作用的，PEP-1介导的HO-1融合蛋白预处理能够明显减轻肝脏缺血再灌注损伤。

Objective To investigate the anti-apoptotie effects of PEP-1-hemeoxygenase-1 （PEP- 1 -HO-1 ） fusion protein on liver ischemia-reperfusion injury in rats. Methods Thirty SD rats were random- ly divided into three groups：sham operation group （group S） , isehemia-reperfusion group （group IR）and PEP-1/ HO-1 ＋ IR group（ group PEP-1 ）. The SD rat＇s liver was subjected to 40 minutes of global ischemia followed by 6 hours of reperfusion. Liver pathology （ HE staining） , HO-1 protein expression （ immunohisto- chemistry） ,liver cell apoptosis （tunnel method and flow eytometry）, Bcl-2 and Caspase-3 expression （ Western blot）were analyzed in liver samples. Results In group IR, the pathological changes of ischemi- a-reperfusion injury were more obvious. In group PEP-1 , the expression levels of HO-1 protein and Bcl-2 were significantly elevated while the cell apoptosis rate and Caspase-3 expression level were significantly decreased. Conclusion There are multi-channel anti-apoptotic effects of PEP-1-HO-1 on the liver ische- mia-reperfusion injury in the model of SD rats,PEP-1-HO-1 fusion protein can obviously decrease the inju- ry severity of liver ischemia-reperfusion.