Prior induction of heat shock proteins by a nitric oxide donor attenuates cardiac ischemia/reperfusion injury in the rat
Prior induction of heat shock proteins by a nitric oxide donor attenuates cardiac ischemia/reperfusion injury in the rat
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DOI：
10.1097/00007890-200006270-00011
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发表时间：
2000-06-27
期刊：
影响因子：
6.2
通讯作者：
Kakita, A
中科院分区：
文献类型：
--
作者：
Katori, M;Tamaki, T;Kakita, A
背景资料。最近的研究表明，一氧化氮(NO)释放剂显著增加了体外细胞系统中的热休克蛋白(HSPs)，提供了对氧化损伤的抵抗力。本研究旨在检测体内移植模型中预先给予NO释放剂FK409(FK)诱导的热休克蛋白的细胞反应。Lewis大鼠于取肾前不同时间点静脉注射生理盐水或FK液(10mU/kg)或再灌流15min(0.66 mU/kg/min)。取组织标本检测HSP70、HO-1/HSP32(HO-1)的表达及谷胱甘肽含量。在威斯康星大学溶液中保存24小时后，进行异位心脏移植，并在14天时测定移植物的存活率。再灌注15min后取材进行DNA末端标记(TdT介导的D-尿苷三磷酸生物素缺口末端标记；TUNEL)和碘化丙啶染色。FK作用后HSP70的基因和蛋白表达分别在12min和60~90min达到高峰，而HO-1的基因和蛋白表达分别在6min和90min达到高峰。然后，在FK治疗60min后，对有代表性的心脏移植物进行进一步的检测。诱导后的HSP70和HO-1分子分别定位于心肌和血管内皮细胞。FK预先治疗能有效防止组织谷胱甘肽含量下降，与对照组比较差异有统计学意义(P
Background. Recent studies have demonstrated that nitric oxide (NO) releasers considerably increase heat shock proteins (HSPs) in the in vitro cell system, providing resistance to oxidant damage. This study was designed to examine the cellular responses of HSPs induced by prior administration of an NO releaser, FK409 (FK), in an in vivo transplantation model.Methods. Lewis rats received either saline or FK solution intravenously administered at different time points before graft harvesting (10 mu mol/kg) or for 15 min during reperfusion (0.66 mu mol/kg/min). Tissue specimens were taken to determine HSP70 and heme oxygenase-1/HSP32 (HO-1) expression, and glutathione content. After 24-hr preservation with University of Wisconsin solution, heterotopic cardiac transplantations were performed, and graft survival was determined at 14 days. Tissue samples for end labeling of nuclear DNA fragments (TdT-mediated d-uridine triphosphate biotin nick end labeling; TUNEL) and propidium iodide staining were taken 15 min after reperfusion.Results. The gene and protein expression of HSP70 after FK administration peaked at 12 min and 60-90 min, whereas those of HO-1 peaked at 6 min and 90 min, respectively. Then, representative cardiac grafts taken 60 min after FK treatment were examined for further assay. Localization of induced HSP70 and HO-1 molecules were observed in the myocardium and vascular endothelium, respectively. Prior treatment of FK was effective in preventing the reduction of tissue glutathione contents compared with control (P