基于DJ-1/mtHsp70/线粒体复合酶Ⅰ/mtROS调控途径探讨白藜芦醇抗心肌缺血再灌注氧化应激损伤的新机制

研究表明白藜芦醇（RSV）能对抗心肌缺血/再灌注（I/R）所诱发的氧化应激，但其分子机制尚未完成阐明。DJ-1作为抗氧化应激蛋白近来被证实在调控线粒体复合体I活性，维持线粒体功能稳定方面起着至关重要的作用。前期工作提示DJ-1似与RSV心肌保护效应存在着内在关联性，但DJ-1是否直接参与RSV抗心肌I/R所诱发的氧化应激及其相应调控机制有待于进一步明确。为此，本研究拟在前期工作基础上，利用一系列分子生物学手段，从体内外多途径多层次进一步明确DJ-1在RSV抗心肌I/R所诱发的氧化应激中的作用。此外，将DJ-1/mtHsp70/复合体I/mtROS有机结合，从DJ-1线粒体内膜亚定位及复合体Ⅰ酶活性调节的全新角度进一步探讨DJ-1介导RSV抗心肌I/R所诱发的氧化应激的分子机制。该研究不仅有助于全面认识RSV心肌保护的作用机制，而且也为研发防治心血管疾病的类似营养素、植物化合物开辟了新思路。

Resveratrol has been demonstrated to elicit cardioprotection by attenuating ischaemia/reperfusion (I/R)–induced oxidative stress injury, but its in-depth molecular mechanism against I/R–induced oxidative stress is not fully understood. DJ-1 is an antioxidative stress protein, which plays a role in maintenance of mitochondrial complex I activity and mitochondrial function. Our preliminary experiments showed that the cardioprotective effect of Resveratrol against hypoxia/reoxygenation (H/R)–induced oxidative stress was accompanied by an enhanced expression of DJ-1 protein and knockdown of DJ-1 abolished the protection, indicating that DJ-1 protein might be closely associated with the cardioprotection of Resveratrol against H/R-induced oxidative stress. However, whether DJ-1 is directly involved in mediating the inhibitory effect of Resveratrol on I/R-induced oxidative stress and its molecular mechanism remains to be further clarified. Therefore, the current investigation will be undertaken to elucidate the role of DJ-1 in the cardioprotection of Resveratrol against I/R-induced oxidative stress by using a variety of molecular biology methods. Additionally, this study will further explore the molecular regulation mechanism by which DJ-1 mediates the cardioprotection of Resveratrol against I/R-induced oxidative stress from the perspective of DJ-1 mitochondrial translocation and modulation of mitochondrial complex I activity at the cellular and whole-animal levels. This study will not only provide new insights into the mechanism underlying the cardioprotective effects of Resveratrol, but also provide new ideas to investigate natural nutrients and plant compounds in prevention and treatment of cardiovascular diseases.