基于CDKN2A/2B基因的细胞周期调控与冠心病证候分类相关机制及中药干预

CHD is a polygenic disease caused by genetic and environmental factors. Vascular smooth muscle cell proliferation is cytopathology mechanism of atherosclerosis. Cell cycle regulation is the final common pathway of hyperplasia. In this study, cell cycle regulation as the key link, the inherent mechanism of TCM intervention and coronary atherosclerosis is discussed from the angle of regulation of cell proliferation, with the use of Yiqi Huoxue intervention. A case-control study is desighed,we genotyped SNPs in the CDKN2A/2B genes and analyzed the relationship between these SNPs and CHD,and its expression in different TCM syndrome types.It Provide molecular evidence for pathogenesis of CHD, and a molecular biological basis for the TCM syndrome differentiation. A randomized controlled design is observed before and after Qishenyiqi pill in the treatment of coronary heart disease with Qi deficiency and blood stasis in treatment of patients with clinical curative effect and the expression of CDKN2A protein. Mechanism is studied by experiment of Qishen Yiqi regulation of VSMCs cell cycle in the treatment of coronary heart disease,to provide new evidence for gene targeting traditional Chinese medicine in the treatment of CHD.

冠心病是一种由遗传因素和环境因素共同作用而发病的多基因遗传性疾病，血管平滑肌细胞（VSMCs）过度增殖是动脉粥样硬化的细胞病理学机制，细胞周期调控机制是增生反应的最终共同通路。 本研究以细胞周期调控为关键环节，采用益气活血中药干预,从细胞增殖调控的角度,探讨冠脉硬化发病的内在机制和中药的干预作用。 采用病例对照设计，分析CDKN2A/2B基因的SNPs，描述其基因型分布特征及在中医不同证型的表现，为冠心病的病理机制提供分子生物学证据，为中医辨证论治提供分子生物学依据。 中药干预采用随机对照设计观察芪参益气丸治疗冠心病气虚血瘀证的临床疗效及患者CDKN2A蛋白治疗前后表达的变化，并通过实验研究观察芪参益气调节VSMCs细胞周期治疗冠心病的作用机理，为中医药防治冠心病提供新理论、新视角和新靶点。

包括项目摘要和结题摘要两部分，项目摘要由信息系统自动生成，内容来源于资助项目计划书；结题摘要由项目负责人填写，应简明扼要地概括出主要研究内容、重要结果及其科学意义等。. 本研究主要研究内容分为：1、证实CDKN2A/2B基因单核苷酸多态性与冠心病遗传易感性及中医不同证型间的相关性；2、芪参益气滴丸能够调节冠心病患者CDKN2A蛋白的表达；3、芪参益气滴丸通过调节细胞周期相关蛋白表达来调控血管平滑肌细胞增殖。本研究结果显示气虚血瘀组与痰浊痹阻组与对照组之间CDKN2A/2B基因SNPs在rs2383206、rs2383207、rs10757274、rs10757278的点位AA、AG、GG均存在统计学差异。30位气虚血瘀证组受试者接受芪参益气滴丸治疗一个月治疗前后血清中miRNA-92a和YKL-40表达水平对比，治疗后的表达水平明显低于治疗前，组间对比有显著差异（P<0.05）。芪参益气滴丸含药血清通过抑制细胞周期蛋白CyclinD1、CDK4蛋白表达，阻滞血管平滑肌细胞周期于G1期，调控细胞周期进程，从而抑制血管平滑肌增殖。初步探索了冠心病发病的分子调控机制及确证新的药物靶点,对进一步阐明冠心病的发病机理、开发新的治疗药物,均具有重要的基础研究意义和应用开发价值。