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Effects of insulin resistance on geranylgeranylacetone-induced expression of heat shock protein 72 and cardioprotection in high-fat diet rats

机译:胰岛素抵抗对高脂饮食大鼠香叶基香叶基丙酮诱导的热休克蛋白72表达及心脏保护的影响

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We investigated the effects of insulin resistance on the expression of heat-shock proteins (HSPs) and myocardial protection against ischemia/reperfusion injury. Male Sprague-Dawley rats received normal chow (CNT) or high-fat (HiF) diet. HiF diet for 6 weeks resulted in the development of insulin resistance, which was evaluated by oral glucose test and insulin tolerance test. Twenty-four hour after oral administration of geranylgeranylacetone (GGA) (200 mg/kg), the heart was isolated and perfused retrogradely with two different doses of insulin (0.1 or 1 mU/ml). Myocardial expression of HSP72 was examined using Western blot analysis. In the HiF group, the expression of HSP72 in response to GGA was decreased. The recovery of left ventricular developed pressure (LVDP) 30 min after reperfusion was tended to be lower in HiF group than in CNT group. Although GGA improved the recovery of LVDP in both CNT and HiF rats, LVDP during reperfusion period was significantly lower in HiF group than in CNT group. High-dose insulin perfusion caused deterioration of post-ischemic functional recovery and LVDP was not different between the two groups, but GGA-induced cardioprotection was preserved irrespective of the dose of insulin both in the CNT and HiF rats. This is the first demonstration that expression of HSP72 was depressed in the heart and that reduced HSP72 was related with less cardioprotection against ischemic insult in high-fat diet-induced insulin resistance rats. (c) 2005 Elsevier Inc. All rights reserved.
机译:我们研究了胰岛素抵抗对热休克蛋白(HSPs)的表达和心肌缺血/再灌注损伤的保护作用。 Sprague-Dawley雄性大鼠接受正常食物(CNT)或高脂(HiF)饮食。 HiF饮食6周导致胰岛素抵抗的发展,这可以通过口服葡萄糖测试和胰岛素耐受测试来评估。口服香叶基香叶基丙酮(GGA)(200 mg / kg)后二十四小时,分离心脏并用两种不同剂量的胰岛素(0.1或1 mU / ml)逆行灌注。使用蛋白质印迹分析检查HSP72的心肌表达。在HiF组中,响应GGA的HSP72表达降低。 HiF组的再灌注后30分钟左室显影压力(LVDP)的恢复倾向于低于CNT组。尽管GGA可以改善CNT和HiF大鼠的LVDP恢复,但HiF组的再灌注期间LVDP明显低于CNT组。大剂量胰岛素灌注引起缺血后功能恢复的恶化,两组之间的LVDP没有差异,但是无论CNT和HiF大鼠中胰岛素的剂量如何,GGA诱导的心脏保护作用都得以保留。这是第一个证明,HSP72的表达在心脏中受到抑制,而HSP72的减少与高脂饮食诱导的胰岛素抵抗大鼠抗缺血性损伤的心脏保护作用降低有关。 (c)2005 Elsevier Inc.保留所有权利。

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