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Up-regulation of hypoxia-inducible factor-1α enhanced the cardioprotective effects of ischemic postconditioning in hyperlipidemic rats
基金项目:This work was supported by grants from the National Nature Scientific Foundation of China (No. 81100150 and No. 81170144) and the Nature Scientific Foundation of Shanxi Province (2012011040-1 ).
摘    要:Hyperlipidemia is an independent risk factor in the devel- opment of ischemic heart disease, which can increase myo- cardial susceptibility to ischemia/reperfusion (I/R) injury. Ischemic postconditioning (PostC) has now been demon- strated as a novel strategy to harness nature's protection against myocardial I/R injury in normal conditions. However, the effect of PostC on hyperlipidemic animals remains elusive. It has been shown in our previous study that PostC reduces the myocardial I/R injury, and hypoxia- inducible factor-1α (HIF-1α) may play an important role in the cardioprotective mechanisms of PostC on normal rats. Here, we tested the hypothesis that the cardioprotec- tion of PostC on hyperlipidemic rats is associated with the up-regulated HIF-1α expression. Male Wistar rats were fed with a high-fat diet for 8 weeks, and then randomly div- ided into five groups: sham, I/R, dimethyloxalylglycine (DMOG) + I/R, PostC, and DMOG + PostC group. The detrimental indices induced by I/R injury included infarct size, plasma creatine kinase (CK) activity and caspase-3 ac- tivity. The results showed that PostC could reduce the infarct size, when compared with the I/R group, which was consistent with the significant lower levels of plasma CK activity and caspase-3 activity, and that it increased the ex- pression of HIF-1α in hyperlipidemic rats. When DMOG was given before PostC to up-regulate HIF-1α protein level, the degree of I/R injury was attenuated. In conclu- sion, these data suggested that the up-regulation of HIF-1α may be one of the cardioprotective mechanisms of PostC against I/R injury in hyperlipidemic rats.

关 键 词:Wistar大鼠  低氧诱导因子-1  缺血  再灌注  高脂血症  保护作用  心脏疾病  后处理  caspase-3
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