心梗发生率和死亡率呈快速上升和年轻化趋势，早期识别高危患者、精确干预、减少心梗发生是我们面临的重大课题。心梗合并糖尿病死亡率是非糖尿病的2.3倍，我们发现其支架术后心血管事件发生率是后者的3.2倍。因此寻找生物标志物以预测糖尿病人心梗发病风险至关重要。课题组前期代谢组学实验显示，糖尿病合并心梗人群脂代谢与糖尿病及健康人相比存在显著差异。文献指出，ApoJ在脂代谢中具有重要作用，课题组前期ApoJ SNPs测定结果也初显出其在三组人群的差异。由此课题组提出ApoJ相关的脂代谢紊乱可能是糖尿病合并心梗的危险因素，并拟应用基因测序和代谢组学技术验证ApoJ、脂质代谢与糖尿病合并心梗的关联性，进而构建风险预测模型；在细胞和动物模型中分别应用RNAi及CRISPR/Cas9基因敲除技术验证ApoJ引起脂代谢变化的通路机制及对糖尿病合并心梗的影响。本研究将为糖尿病合并心梗的防治及机制研究提供重要依据。

In recent years, the morbidity and mortality of myocardial infarctin(MI) are sharply rising ,and the age of this population is younger. More and more medical resources have been consumed on MI. The early identification, intervention and treatment for the patients at high risk are big challenges facing us. Researches showed that the mortality of MI patients with diabetes is 2.3 times of those without diabetes, and those MI patients with diabetes have more possibilities to get cadiovascular diseases after the PCI treatment. Therefore, the identification of effective biomarkers is critical for early intervention and treatment that can delay and/or prevent MI. In the preliminary studies, we found that concentration of many lipids showed significant differences among the diabetes with MI, the diabetes and the control groups based on metabonomics research. Previous researches reported that ApoJ was essential to the lipid metabolism,and our preliminary results provide the idea that ApoJ gene mutation was a risk factor for diabetes with MI. To obtain specific biomarkers , the approach of genotype sequencing and UPLS-MS will be applied , then a risk prediction model for ApoJ genotypes, lipid metabolism and T2DM with MI will be established. RNAi technique and CRISPR/Cas9 genome editing system will be used in the cell and mice model experiments to show the affection of ApoJ to lipid metabolism pathway and the development of diabetes with MI. This study will provide important basis for intervention and treatment of diabetes with MI.

心血管疾病已成为威胁人类健康的第一大杀手，我国目前有心血管疾病患者2.9亿，每年约350万人死于各类心血管疾病，平均每十秒就有一个患者死于这一疾病，而其中急性心肌梗死死亡率呈现快速上升和年轻化趋势。心梗合并糖尿病死亡率是非糖尿病的2.3倍，我们发现其支架术后心血管事件发生率是后者的3.2倍。如何精确定位糖尿病患者中心梗的高发人群，及对这部分人群的心血管进行精准的风险评估，以利于早期发现早期干预，是我们面临的严峻课题。然而，目前关于糖尿病合并心肌梗死生物标志物的发现及其发生发展机制的研究尚不明确。因此，寻找糖尿病患者发生心梗的生物标志物以早期预测发病风险，改变该人群的治疗和预防方案，减少心梗的发生至关重要。本课题组完善并建立了血清样本的 UPLC-MS 组学检测方法，筛查出在糖尿病合并心梗患者血液样本中显著升高的棕榈酸、硬脂酸及花生四烯酸三种脂质代谢物变化，进而扩大样本量对三种脂质进行靶向检测，确定了糖尿病合并心梗的早期发现的量化标准。本研究不仅为针对糖尿病合并心梗患者进行脂质小分子物质的代谢组学研究提供了有力证据，更为脂质代谢在糖尿病合并心梗的发生发展机制研究提供了理论和实验依据。