1. 研究目的与意义
一、研究内容:本课题研究VSMC表型转换的具体内在机制，及myocardin在动脉粥样硬化中所起的保护作用是否涉及myocardin对平滑肌细胞表型转换的影响，探讨丹皮酚抑制平滑肌细胞表型转换是否需要myocardin的参与，以及观察myocardin是否与ERα相结合而作用于VSMC的表型转换等问题。
二、研究意义: VSMC由收缩型向合成型转换是VSMC迁移与增殖的前提，当血管受到损伤或刺激，可促进VSMC从收缩表型转换成合成表型，从而影响血管结构和功能，促进AS的发展。
所以，维持VSMC的收缩表型对抑制其增殖有一定的促进作用，并可改善AS的病理过程。
2. 文献综述
参考文献1.Chistiakov D A, Orekhov A N, Bobryshev Y V. Vascular smooth muscle cell in atherosclerosis[J]. Atherosclerosis, 1998, 138(1):3-9.2..Sartore S, Chiavegato A, Faggin E, et al. Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant[J]. Circ Res, 2001, 89: 1111-1121.3.Zhang M J, Zhou Y, Chen L, et al. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation[J]. Histochemie, 2015, 145(2):119-130.4.Martin KA, Rzucidlo EM, Merenick BL, et al. The mTOR/ p70S6K1 pathway regulates vascular smooth muscle cell differentiation[ J]. Am J Physiol Cell Physiol, 2004, 286:5.Alexander MR,Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease[J]. Annu Rev Physiol, 2012, 74: 13-40.6.Jiang H, Lun Y, Wu X, et al. Association between the hypomethylation of osteopontin and integrin β3 promoters and vascular smooth muscle cell differentiation in great saphenous varicose veins[J]. Int J Mol Sci, 2014, 15: 18747-18761.7.Wagner RJ,Martin KA, Powell RJ, et al. Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR[J].Am J Physiol Cell Physiol, 2010, 299: C119-127.8.Won Sun Park, Soon Chul Heo, Eun Su Jeon, et al.Functional expression of smooth muscle-specific ion channels in TGF-β -treated human adipose-derived mesenchymal stem cells[J]. Am J Physiol Cell Physiol, 2013, 305(4): C377C391.9.Li P,Zhu N, Yi B, et al. MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascula smooth muscle cell phenotypic switch and vascular neointimal formation[J]. Circ Res, 2013, 113: 1117-1127. 10.方立, 陈美芳, 余国龙, 等. 内皮祖细胞对血管紧张素2 诱导的血管平滑肌细胞表型转化的影响[J]. 中国动脉硬化杂志, 2009, 17: 459-464.11.Austin KM,Nguyen N, Javid G, et al. Noncanonical matrix metalloprotease-1-protease-activated receptor-1 signaling triggers vascular smooth muscle cell dedifferentiation and arterial stenosi[J]. J Biol Chem, 2013, 288: 23105-23115.12.Yu Z H, Wang Y X, Song Y, et al. Up-regulation of KCa3.1 promotes human airway smooth muscle cell phenotypic modulation[J]. Pharmacological Research, 2013, 77(15):30-38.13.Sullivan TR Jr ,Karas RH , Aronovitz M , et al .Estrogen inhibits the response-to-injury in a mouse earotid artery model[ J] .Clin Invest , 1995 ,96(5):2482-2487 .14.Risinger GM Jr. , Updike DL, Bullen EC, et al. TGF-beta suppresses the upregulation of MMP-2 by vascular smooth muscle cells in response to PDGF-BB[J]. Am J Physiol Cell Physiol,2010, 298: C191-201.
3. 设计方案和技术路线
4. 工作计划
1.通过查阅文献对VSMC表型转化有了基本认识，并且研究了六味地黄方抗动脉粥样硬化作用及分子机制。
2.根据设计的方案进行实验。
3.整理实验数据。
5. 难点与创新点
本课题应用多种先进的分子生物学技术手段，如Western blot、Real-time PCR、免疫荧光染色等，且还运用多种先进仪器荧光显微镜等。
相比于传统的实验方法具有速度快、运用范围广的优点，能弥补实验方法难以克服的缺点。
