Horikawa Saburo, Yoneya Rika, Nagashima Yoji, Hagiwara Kiyokazu, Ozasa Hisashi
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, Japan.
FEBS Lett. 2002 Jan 16;510(3):221-4. doi: 10.1016/s0014-5793(01)03270-7.
Heme oxygenase (HO)-1 catalyzes the rate-limiting step in heme degradation releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an adaptive and protective response to oxidative stress. Ischemia and reperfusion (IR) injury seems to be mainly caused by the oxidative stress. In this study, we have examined whether prior induction of HO-1 with buthionine sulfoximine (BSO), a glutathione (GSH) depletor, affects the subsequent renal IR injury. BSO (2 mmol/kg body weight) was administered intraperitoneally into rats, the levels of HO-1 protein increased within 4 h after the injection. When BSO was administered into rats at 5 h prior to the renal 45 min of ischemia, the renal IR injury was assessed by determining the levels of blood urea nitrogen and serum creatinine, markers for renal injury, after 24 h of reperfusion. The renal injury was significantly improved as compared to the rats treated with IR alone. Administration of zinc-protoporphyrin IX, an inhibitor of HO activity, reduced the efficacy of BSO pretreatment on the renal IR injury. Our findings suggest that the prior induction of HO-1 ameliorates the subsequent renal IR injury.
血红素加氧酶（HO）-1催化血红素降解的限速步骤，释放出铁、一氧化碳和胆绿素。HO-1的诱导作为对氧化应激的一种适应性和保护性反应而发生。缺血再灌注（IR）损伤似乎主要由氧化应激引起。在本研究中，我们检测了用谷胱甘肽（GSH）消耗剂丁硫氨酸亚砜胺（BSO）预先诱导HO-1是否会影响随后的肾脏IR损伤。将BSO（2 mmol/kg体重）腹腔注射给大鼠，注射后4小时内HO-1蛋白水平升高。当在肾脏缺血45分钟前5小时给大鼠注射BSO时，在再灌注24小时后，通过测定血尿素氮和血清肌酐水平（肾脏损伤标志物）来评估肾脏IR损伤。与仅接受IR治疗的大鼠相比，肾脏损伤得到显著改善。给予HO活性抑制剂锌原卟啉IX降低了BSO预处理对肾脏IR损伤的疗效。我们的研究结果表明，预先诱导HO-1可改善随后的肾脏IR损伤。
