上转化纳米颗粒复合物介导的光动力促进动脉粥样硬化不稳定斑块内巨噬细胞型别转换的机制

Nowadays, aging population is growing and normal diet is changing.More and more people get atherosclerosis. This study aims to solve the problems presenting in expensive artery stenting, endarterectomy,bypass surgery for atherosclerosis.So a simple ,valid and popular method for atherosclerosis is expected by people.During the process of atherosclerosis the important link is to reduce the plague formation or stablize the plague.Our previous study first proved that photodynamic therapy induce the macrophage phenotype in the atherosclerosis plague..Our previous studies have solved the problem via body surface with PDT and demonstrated that photodynamic therapy (PDT) has the capability to induce foam cells' apoptosis through the mitochondrial pathway by activating the protoporphyrin Ⅸ (PpⅨ) which bind on the mitochondrial specifically. And the apoptosis of foam cells promotes the plaque to decrease and stability.we hypothesis that PDT can induce apoptosis of foam cells through mitochondrial pathway, which activate the macrophage by releasing bunch of ATP, increasing S1P and differentiating macrophage into M2 .The macrophage engulf function is enhanced, which makes plague from the unsteady state to steady state..This study will confirm above mentioned theory and hypothesis by molecular biology,cytobiology, immunohistochemistry and etc.This study involves in the chemistry,physics and medicine. .This study has theoretical significance, clinical values and the prospects for industrialization.

随着人口老龄化和日常饮食结构的改变，动脉粥样硬化(AS)患者日趋增多，除昂贵的介入和搭桥术治疗AS外，寻求一种简单、有效和易于推广的方法，是人们所期待的。在AS发病过程中，减少斑块形成或稳定斑块，是治疗AS的重要环节。在前期工作我们首次证实，光动力促进动脉粥样硬化斑块内巨噬细胞型别转换，证实光动力治疗（PDT）通过激活特异性结合在线粒体上的光敏剂，诱导泡沫细胞发生线粒体凋亡，能够起到减小和稳定斑块的作用。本项目提出假设：PDT能够通过诱导AS不稳定斑块内泡沫细胞发生线粒体凋亡，释放大量ATP，使S1P增加，促进单核巨噬细胞向稳定的M2型巨噬细胞分化，并且增强了斑块内吞噬清除功能，有利于不稳定斑块变成稳定斑块。拟通过培养泡沫细胞和载脂蛋白E基因敲除小鼠AS斑块模型，应用分子生物学等技术来证实上述假设。本项目涉及化学、物理学、医学等多学科交叉研究，有理论意义、临床价值和产业化前景。

随着人口老龄化和日常饮食结构的改变，动脉粥样硬化(AS)患者日趋增多，除昂贵的介入和搭桥术治疗AS外，寻求一种简单、有效和易于推广的方法势在必行。以动脉粥样硬化斑块发生发展的免疫学机制为基础，将“上转换纳米材料介导的光动力治疗应用于动脉粥样硬化疾病”。光动力治疗是利用激光的物理能量激活特定药物发生化学反应，产生活性氧，从而发挥生物学效应的一种无创治疗方法。本研究合成上转换纳米颗粒包覆的光敏剂（将波长高的激发光转换为可激活光敏剂的光）复合物，利用波长高的激光穿透能力强的特性，解决传统光动力穿透深度浅的缺陷。筛选出了适合上转换材料的光敏剂，证明了上转换纳米颗粒介导的光动力对巨噬细胞、泡沫细胞以及ApoE-/-小鼠有治疗作用，能够无创通过诱导AS 不稳定斑块内泡沫细胞发生线粒体凋亡、促进单核巨噬细胞向型别转换、增强了斑块内促胆固醇流出清除功能，有利于不稳定斑块变成稳定斑块。本项目涉及化学、物理学、医学等多学科交叉研究，有理论意义、临床价值和产业化前景。.申请国家专利4项，已授权2项。发表国内外文章14篇（SCI文章11篇、中文核心3篇），其中IF≥5.0 SCI文章2篇，IF≥4.0 SCI文章5篇。培养博士后出站1名，博士毕业2名，硕士毕业4名。参加国际学术会议5次（美国、台湾、日本、香港、阿根廷），并获ISHR Travel Award。国际会议专题报告1次，国内专题报告9次。