Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart
Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart
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DOI：
10.1161/hc3901.095771
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发表时间：
2001-10-09
期刊：
影响因子：
37.8
通讯作者：
Sakata, T
中科院分区：
文献类型：
--
作者：
Ooie, T;Takahashi, N;Sakata, T
背景：热休克蛋白（HSPs）的诱导对心肌缺血损伤具有保护作用。香叶乙酸酮（GGA）是一种抗溃疡剂，据报道可在大鼠胃黏膜和小肠中诱导HSP72。本研究验证了口服GGA可诱导大鼠心脏产生HSP72，从而对心肌缺血再灌注损伤具有保护作用的假设。方法与结果：采用Western blot方法定量检测大鼠心脏热休克蛋白的表达。全身热疗10分钟可诱导大鼠心脏中HSP72的表达。单次口服GGA （200 mg/kg）也能诱导HSP72的表达，在给药后24小时达到峰值。因此，在给药200 mg/kg GGA （GGA组）或对照体（对照组）24小时后，采用Langendorff仪进行离体灌注心脏实验。5分钟稳定期后，给予无血流全脑缺血20、40或60分钟，然后再灌注30分钟。再灌注时，GGA组功能恢复较对照组大，肌酸激酶释放量较对照组少。电镜观察结果显示，gga处理后心肌细胞缺血/再灌注损伤被阻止。结论：口服GGA通过诱导HSP72对心肌缺血损伤具有保护作用。
Background-Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats.Methods and Results-Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes.Conclusions-The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.