钾离子通道Kir2.1调控血管损伤后血管平滑肌细胞表型转换的作用及其机制

血管平滑肌细胞（VSMC）表型转换、过度增殖和迁移是冠脉介入治疗术后再狭窄的主要原因。我们前期研究发现VSMC由收缩表型向合成表型转换时内向整流钾离子通道2.1（Kir2.1）表达增加伴随整合素连接激酶（ILK）表达下调。我们推测Kir2.1表达上调引起ILK表达减少，通过抑制PI3K/ILK/Akt/GSK3β信号通路诱导VSMC由收缩表型向合成表型转换。本研究通过构建Kir2.1过表达和沉默表达的腺病毒质粒，转染VSMC，观察不同VSMC胞浆内PIP2、ILK/Kir2.1表达的差异；在体血管内转染Kir2.1不同质粒的病毒液，明确Kir2.1对血管损伤后新生内膜增生的影响；采用膜片钳、钙离子成像和分子生物学技术，揭示Kir2.1通过抑制PI3K/ILK/Akt/GSK3β信号通路调控VSMC表型转换的机制，以验证我们的假说。为防治冠脉介入术后再狭窄提供重要的药物靶点和电生理学依据。

Switching from a differentiated/contractile to a dedifferentiated/synthetic phenotype, the increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of artery restenosis after percutaneous coronary intervention. Our previous studies have shown that the level of Inwardly Rectifying K Channel 2.1(Kir2.1) is up-regulated during the phenotypic switching from the contractile to synthetic phenotype, accompanied with the down-regulation of integrin linked kinase(ILK). We speculate that the enhanced expression of Kir2.1 can promote the VSMC transition from the contractile to a synthetic phenotype by down regulation the expression of ILK through the inhibition of PI3K/ILK/Akt/GSK3β pathway. In order to verify our hypothesis, we will transfect VSMC with constructing recombinant adenovirus vectors for Kir2.1 gene overexpression and gene silence to observe the expression of PIP2, ILK/Kir2.1; transfection in vivo to rat carotid arteries will be used to discover how kir2.1 affect the neointimal hyperplasia after vascular injury; patch clamp, calcium imaging and molecular biology techniques will be used to revel the mechanism of kir2.1 regulating the VSMC phenotype by blocking PI3K/ILK/Akt/GSK3β signaling pathway. We will provide another new important drug targets and electrophysiology theoretical basis for the prevention of restenosis after coronary intervention.