Yamashita N, Hoshida S, Nishida M, Igarashi J, Aoki K, Hori M, Kuzuya T, Tada M
First Department of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565, Japan.
J Mol Cell Cardiol. 1997 Jul;29(7):1815-21. doi: 10.1006/jmcc.1997.0416.
We compared the time course of tolerance to myocardial ischemia-reperfusion injury with the time course of heat shock protein 72 (hsp72; inducible form) induction after heat stress in a rat model. The size of the infarct resulting from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42 degrees C for 15 min), but was significantly decreased 48 and 72 h after hyperthermia, compared with the sham control. The infarct size was decreased as late as 96 h after hyperthermia, although the infarct-limiting effect was smaller at that time. The myocardial content of hsp72 was markedly increased for 3-72 h after hyperthermic treatment, and was decreased after 72 h in association with an increase in the infarct size. The hsp72 content remained elevated during the period of tolerance to ischemia-reperfusion injury, but the infarct size decreased after the hsp72 content peaked. Pretreatment with a protein kinase C (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia, significantly suppressed the delayed cardioprotective effect of hyperthermia and reduced hsp72 induction. These results suggest that newly synthesized hsp72 through PKC activation after heat stress may have to be post-translationally modified and compartmentalized prior to assuming to the development of the delayed tolerance to ischemia-reperfusion injury in rats.
我们在大鼠模型中比较了心肌缺血再灌注损伤的耐受时间进程与热应激后热休克蛋白72（hsp72；诱导型）诱导的时间进程。全身热疗（42℃，15分钟）后12小时，缺血再灌注导致的梗死面积增加，但与假手术对照组相比，热疗后48小时和72小时梗死面积显著减小。热疗后96小时梗死面积仍减小，尽管此时梗死限制效应较小。热疗后3 - 72小时心肌hsp72含量显著增加，72小时后随着梗死面积增加而降低。在对缺血再灌注损伤的耐受期内，hsp72含量持续升高，但在hsp72含量达到峰值后梗死面积减小。热疗前立即用蛋白激酶C（PKC）抑制剂氯化白屈菜红碱预处理，可显著抑制热疗的延迟心脏保护作用并减少hsp72诱导。这些结果表明，热应激后通过PKC激活新合成的hsp72在对大鼠缺血再灌注损伤产生延迟耐受之前可能必须进行翻译后修饰并分隔化。
