中文摘要
传统中药调控病理性血管新生的作用机制尚未完全阐明。前期研究发现,麝香保心丸能够促进缺血心肌区域血管新生,同时抑制斑块内血管新生相关因子表达。运用和实践中医整体理论,基于药物多靶点作用的思考,我们提出假说:在动脉粥样硬化进程和心肌梗死修复过程中,单核细胞亚群介导的固有免疫参与调控斑块和缺血心肌中的血管新生;麝香保心丸通过调节单核细胞募集、定居和亚型转化,动态差异性调控不同组织病理背景下的血管新生。我们建立ApoE-/-小鼠动脉粥样硬化和急性心肌梗死动物双模型,证实麝香保心丸通过单核细胞亚群动态差异性调控病理性血管新生;运用CX3CR1-/-和CCR2-/-小鼠验证趋化因子受体参与调控血管新生;免疫磁珠分选单核细胞亚群并在Transwell系统中分别与内皮细胞和成纤维细胞共培养,探讨不同单核细胞亚群差异性调控血管新生的内在机制。课题研究将为中药临床治疗冠心病提供新靶点。
英文摘要
The inner mechanism how traditional Chinese medicine regulates pathological angiogenesis has not been entirely elucidated. Our previous studies have demonstrated that Shexiang Baoxin Pill(SBP) shows distinct regulation effects, which promotes ischemic myocardial angiogenesis, while inhibits the expression of angiogenesis related factors in atherosclerotic plaque. By practicing the holistic theory of traditional Chinese medicine, also considering its multiple-target effects, we proposed a hypothesis: in the process of atherosclerosis, myocardial infarction and subsequent repairment, the intrinsic immune mediated by monocytes participates in the regulation of the angiogenesis in atherosclerotic plaque and ischemic myocardium; through the regulation of recruitment, settlement and transformation of different monocyte subtypes, SBP is assumed to adjust pathological angiogenesis dynamicly in different tissue. The new animal model of ApoE -/- mice suffered atherosclerosis and acute myocardial infarction is to be built to confirm that SBP regulates pathological angiogenesis via distinct monocyte subsets; The CX3CR1-/-和CCR2-/- mice are applied to verify the effect of chemokine receptor in angiogenesis. Different monocyte subsets are separated by MACS technology and co-cultured with endothelial cells and cardiac fibroblasts in the Transwell contact system to investigate inherent mechanism. This systematic study will provide a novel target for clinical treatment for coronary heart disease.
