LDL受体基因缺陷仓鼠血管内膜损伤后狭窄模型--拟人化血管重塑性疾病模型的建立及其干预

仓鼠是和人类更加相似的非灵长类小型动物，是人类心血管疾病的极佳动物模型。低密度脂蛋白受体敲除（LDLR KO）仓鼠与人类动脉粥样硬化疾病具有相似的病理特征和病理机制。另外，小檗碱（BBR）具有降低胆固醇和抑制血管平滑肌细胞增殖的作用。目前，我们成功建立了LDLR KO仓鼠血管内膜损伤后狭窄模型，本项目拟以此为基础，通过联合利用多组学分析，系统地比较LDLR KO仓鼠、LDLR-/-小鼠血管内膜损伤模型的再狭窄血管以及人类动脉粥样硬化病变血管，确认该仓鼠模型的表型特点和优势，建立新型的血管重塑疾病动物模型。并且，本项目将比较BBR与其他化学合成药的药效，明确LDLR KO仓鼠内膜损伤模型在抗血管重塑性疾病新药研发上的应用价值。本项目的实施将建立拟人化小型血管重塑性疾病动物模型，为不适合使用大小鼠的研究提供新的模式动物平台，开创和引领一个拟人化的小型心血管疾病动物模型新领域。

Hamster is an excellent animal model of the human cardiovascular disease, cause its plasma lipoprotein profile and high-fat diet reaction is closer to humans. LDL receptor knockout (LDLR KO) hamster and human atherosclerotic disease have similar pathological and pathological mechanisms. Furthermore, Berberine (BBR) reduced rat cholesterol and inhibited vascular smooth muscle cell proliferation. Now, we have successfully established arterial restenosis model after injury in LDLR KO hamster. In this project, we will compare arteries from LDLR-/- mice after arterial injury, LDLR KO hamster after arterial injury and human atherosclerosis using transcriptomics, proteomics and metabolomics analysis. We want to clear the phenotypic characteristics and advantages of LDLR KO hamster model after arterial injury in the vascular remodeling disease. Moreover, We will compare the efficacy of BBR and synthetic drugs, and clear the value of LDLR KO hamster intimal injury model in the development of anti-angiogenic remodeling disease drug. This project will provide a the new small animal model of vascular remodeling disease, which is not suitable for animal studies using rats and mice, and lead a new small animal model in cardiovascular disease.