白藜芦醇调节STIM1抑制血管平滑肌细胞增殖机制的探讨

The excessive proliferation, migration and phenotypic changes of VSMC is the main pathologic basis for AS formation, and SOCE-induced [Ca2 +] i change is the key factor in triggering cell proliferation and migration-related signal transduction.In this study,we will combine the latest research achievements of resveratrol, and explore whether resveratrol can inhibit VSMCs proliferation by decreasing calcium influx through affecting SOCs formation , and this effect whether mediated by ER. This research can help us to identify the cardiovascular protection mechanisms of resveratrol, to provide a theoretical basis for clinical application to provide a theoretical basis, also it can offer a new strategies for AS prevention.

VSMCs过度增殖迁移及表型转变是AS形成的主要病理基础，且SOCE诱导的[Ca2+]i的变化是触发细胞增殖迁移相关信号转导的关键因素。本研究将结合植物性雌激素白藜芦醇的新近研究进展，探讨白藜芦醇是否可以通过调节STIM1，影响SOCs形成，抑制钙内流发挥其抑制VSMCs增殖的抗AS效应，且此效应是否由ER介导。此问题解决有助于明确白藜芦醇的心血管保护机制，并对及其临床应用提供理论依据，并为AS防治提供新的对策。

心血管疾病是危害我国人民健康的重要疾病，VSMCs过度增殖迁移及表型转变是AS形成的主要病理基础，且SOCE诱导的[Ca2+]i的变化是触发细胞增殖迁移相关信号转导的关键因素。本研究建立鼠AS模型，利用免疫荧光，免疫组化，WB，realtimePCR等方法探讨白藜芦醇是否可以通过调节STIM1，影响SOCs形成，抑制钙内流发挥其抑制VSMCs增殖的抗AS效应。结果显示：模型组动脉粥样硬化斑块明显、STIM1荧光增强，而白藜芦醇预处理可明显抑制斑块形成，降低STIM1荧光强度；同时，WB及realtimePCR结果提示，与模型组相比，白藜芦醇组可明显降低STIM1，Orai1表达。在体外培养的VSMCs中，WB及realtimePCR结果显示白藜芦醇可降低血清诱导的STIM1，Orai1表达增加；钙离子浓度测定显示，白藜芦醇可以抑制外钙内流现象，此结果提示白藜芦醇可以通过抑制STIM1及Orai1表达，抑制SOCE诱导的钙内发挥抗动脉粥样硬化效应。实验结果同时显示，白藜芦醇预处理可以增加ERα表达，且此效应可被ICI182,780阻断，提示白藜芦醇的抗动脉粥样硬化效应由ERα介导。