Inhibition for the Low Flow Hypoxia-Induced Mitochondrial Dysfunction using Methylprednisolone and Bcl-2

1 Bcl-2定位Bcl-2在一些细胞系中存在于线粒体、内质网和核膜中，在正常人和大鼠肝脏中不表达。我们报道Bcl-2在正常大鼠肝脏中表达，并且主要位于线粒体的内膜和嵴而不是外膜缺氧诱导的线粒体Bcl-2下降。在低流量缺氧大鼠肝脏的中间区，观察到凋亡的非实质细胞，鉴定为SECs，而很少有实质细胞凋亡。天花板被弄脏了。缺氧时线粒体Bcl-2水平明显下降，但未见明显凋亡形态学迹象。特异性黄嘌呤氧化酶抑制剂预处理可阻断过氧化氢的产生，也可阻断缺氧诱导的secs细胞凋亡和线粒体Bcl-2的下降30 mg/kg、10mg/kg或3 mg/kg甲基强的松龙预处理可抑制缺氧诱导的线粒体膜去极化和酶渗漏，但对窦状内皮细胞的过氧化氢水平和凋亡没有影响。甲基强的松龙的有益作用似乎与其在缺氧条件下防止线粒体膜去极化的能力有关。

1 Bcl-2 localizationBcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. We report that Bcl-2 is expressed in normal rat liver, and located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.2 The hypoxia-induced mitochondrial Bcl-2 declineThe apoptotic nonparenchymal cells, identified as SECs, were observed, predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchyma! ceils were stained. Mitochondrial Bcl-2 levels declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. Pretreatment with a specific xanthine oxidase inhibitor blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.3 The mechanism by which methyiprednisolone protects the ischermic liverPretreatment with 30 mg/kg, 10mg/kg or 3 mg/kg methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization, and enzyme leakage, though hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. The beneficial effect of methylprednisolone appears to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.