原花青素对大气细颗粒物暴露所致心血管损伤的保护作用及其机制研究

Air pollution is an important public health problem that we had to faced in recent years, Beijing-Tianjin-Hebei is still the region with most severe haze in China. Haze is an important risk factor for human health. Therefore, how to prevent the damage has become a top priority for public health workers. Procyanidin had good application prospects in the prevention of cardiovascular diseases. The effect of procyanidin reduces myocardial tissue and vascular smooth muscle cells damage of rats caused by exposure to PM2.5 was found in our previous experiments, it is suggested that procyanidin has protective effects on the cardiovascular system of rats exposed to PM2.5, but its possible mechanism are not clear. We will conduct research at cellular level and animal level to observe the positive effect of procyanidin on the vascular damage induced by PM2.5 exposure, and to reveal the regulatory mechanism of the positive effect of procyanidin on cardiovascular injury and vascular smooth muscle cell apoptosis caused by PM2.5 via "Oxidative Stress (ROS) - Granzyme B - Casepase-3 - PARP" signaling pathway. This study will lay a theoretical foundation for the prevention of cardiovascular damage caused by PM2.5 using procyanidins, and provide support for the prevention of PM2.5 damage through diet.

大气污染是我国近些年面临的重要公共卫生问题，而京津冀地区是全国雾霾最典型的区域。雾霾严重威胁着人群健康，预防雾霾对人体健康造成的损害成为公共卫生工作者的当务之急。食物中的原花青素在预防心血管疾病方面已经展示出良好的应用前景。我们前期的实验发现，原花青素能够减轻PM2.5暴露所造成的大鼠心肌组织和血管平滑肌细胞的损伤，提示原花青素对PM2.5暴露所致的大鼠心血管系统损伤有保护作用，但是其潜在的作用机制并不清楚。本研究将从细胞和动物两个水平开展干预研究，观察原花青素对PM2.5暴露所致血管损伤的改善作用，探讨原花青素经“氧化应激（ROS）—颗粒酶B—Casepase-3—PARP”信号途径改善PM2.5引起的心血管组织损伤和血管平滑肌细胞凋亡的调控机制。该研究将为原花青素类植物化学物防治PM2.5所致心血管损伤奠定理论基础，同时为通过膳食预防PM2.5损伤提供科学依据。

细颗粒物（PM2.5）暴露的增加与心血管疾病的发生发展密切相关，而原花青素具有很强的抗氧化，对多种心血管疾病具有明显的抗氧化作用。然而，尚未有研究探讨原花青素对PM2.5诱导的心血管疾病的作用及其机制。本课题以血管平滑肌细胞和大鼠为研究对象，建立了PM2.5致血管平滑肌细胞和大鼠损伤的模型，采用免疫组化、western blot等技术深入研究了原花青素干预PM2.5诱导心血管损伤的主要作用靶点。在体内，PM2.5暴露显著提高了ROS和MDA的含量，并降低了SOD活性，而原花青素干预后增加了Nrf2及其下游抗氧化剂基因的表达，减轻了氧化应激和血管凋亡。在体外，PM2.5诱导的VSMCs细胞毒性呈剂量依赖性，而原花青素通过激活Nrf2信号通路来减轻氧化应激和细胞凋亡。本研究为深入研究预防PM2.5诱导的心血管损伤提供新思路和理论依据。