Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin
Pharmacological hepatic preconditioning: involvement of 70-kDa heat shock proteins (HSP72 and HSP73) in ischaemic tolerance after intravenous administration of doxorubicin
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DOI：
10.1046/j.1365-2168.2000.01509.x
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发表时间：
2000-09-01
影响因子：
9.6
通讯作者：
Yamaoka, Y
中科院分区：
文献类型：
--
作者：
Kume, M;Yamamoto, Y;Yamaoka, Y
背景：药物预处理可诱导应激反应，保护肝脏免受缺血再灌注损伤（IRI）。本研究的目的是确定，在动物模型中，是否静脉注射阿霉素诱导肝组织中的热休克蛋白（HSP），促进肝脏耐受随后的温暖IRI.Methods：雄性Wistar大鼠。在注射阿霉素1 mg/kg体重后，依次测定肝组织中热休克蛋白的产生。在用阿霉素预处理（48小时前）的动物和对照组中测定了30分钟热缺血和肝脏再灌注的耐受性。记录再灌注40 min后肝功能、肝腺苷酸浓度及缺血后7 d的存活率。结果：阿霉素给药48 h后，肝脏中HSP 72和HSP 73表达明显增加。生化参数和生存率显着更好的预处理动物比controls.Conclusion：这些结果表明，阿霉素有潜力提供肝脏对IRI的耐受性。肝组织中HSP 72和HSP 73的同时增加可以解释阿霉素给药后耐受性的获得。
Background: Pharmacological preconditioning may induce a stress response which protects liver against ischaemia-reperfusion injury (IRI). The aim of this study was to determine, in an animal model, whether intravenous administration of doxorubicin induces heat shock proteins (HSPs) in liver tissue and facilitates liver tolerance to subsequent warm IRI.Methods: Male Wistar rats were used. Production of HSPs was determined in liver tissue sequentially after the injection of doxorubicin 1 mg/kg body-weight. Acquisition of tolerance for 30 min warm ischaemia and reperfusion of the liver was determined in animals pretreated (48 h beforehand) with doxorubicin, and in controls. Biochemical liver function and liver adenine nucleotide concentration 40 min after reperfusion and survival rate at 7 days after the ischaemic insult were recorded.Results: Expression of HSP72 and HSP73 in the liver was confirmed 48 h after doxorubicin administration. Biochemical parameters and survival rates were significantly better in pretreated animals than in controls.Conclusion: These results indicate that doxorubicin has the potential to provide the liver with tolerance against IRI. A simultaneous increase of both HSP72 and HSP73 in liver tissue may explain the acquisition of tolerance following the administration of doxorubicin.