Effects of insulin resistance on geranylgeranylacetone-induced expression of heat shock protein 72 and cardioprotection in high-fat diet rats.
Effects of insulin resistance on geranylgeranylacetone-induced expression of heat shock protein 72 and cardioprotection in high-fat diet rats.
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DOI：
10.1016/j.lfs.2004.12.034
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发表时间：
2005-07
期刊：
影响因子：
6.1
通讯作者：
T. Ooie;Munetaka Kajimoto;N. Takahashi;T. Shinohara;Yayoi Taniguchi;H. Kouno;O. Wakisaka;H. Yoshimatsu;T. Saikawa
中科院分区：
文献类型：
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作者：
T. Ooie;Munetaka Kajimoto;N. Takahashi;T. Shinohara;Yayoi Taniguchi;H. Kouno;O. Wakisaka;H. Yoshimatsu;T. Saikawa
我们研究了胰岛素抵抗对热休克蛋白（HSP）表达和心肌缺血/再灌注损伤保护的影响。雄性 Sprague-Dawley 大鼠接受正常饮食 (CNT) 或高脂肪 (HiF) 饮食。 6周的HiF饮食导致胰岛素抵抗的发生，通过口服葡萄糖试验和胰岛素耐量试验来评估。口服香叶基香叶基丙酮（GGA）（200 mg/kg）24小时后，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。再灌注后30分钟左心室展开压(LVDP)恢复情况HiF组比CNT组有较低趋势。尽管GGA改善了CNT和HiF大鼠的LVDP恢复，但HiF组在再灌注期间的LVDP显着低于CNT组。高剂量胰岛素灌注导致缺血后功能恢复恶化，两组之间的 LVDP 没有差异，但在 CNT 和 HiF 大鼠中，无论胰岛素剂量如何，GGA 诱导的心脏保护作用均得以保留。这是首次证明 HSP72 的表达在心脏中受到抑制，并且 HSP72 的减少与高脂肪饮食诱导的胰岛素抵抗大鼠中针对缺血性损伤的心脏保护作用减弱有关。
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.