蛋白酶体抑制剂Bortezomib对肺动脉平滑肌细胞钙离子通路的作用研究

项目名称： 蛋白酶体抑制剂Bortezomib对肺动脉平滑肌细胞钙离子通路的作用研究

项目编号： No.81460011

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 徐磊

作者单位： 内蒙古医科大学

项目金额： 40万元

中文摘要： 肺动脉高压是严重威胁人类健康的一大类疾病，肺动脉平滑肌细胞内钙离子浓度增高进而导致肺动脉重塑是肺动脉高压发病机制的核心环节。蛋白酶体抑制剂Bortezomib可以降低多种肺动脉高压动物模型的肺动脉的压力，减轻肺动脉重塑，然而Bortezomib是否通过钙离子这个环节发挥作用仍不清楚，我们拟通过低氧性肺动脉高压大鼠模型，探讨蛋白酶体抑制剂对肺动脉平滑肌钙离子通道的影响以及与平滑肌细胞增殖迁移的关系。低氧时通过PPARγ-TRPC1，6信号通路使钙池操控性钙内流（SOCE）增加，进而可以导致肺动脉平滑肌细胞内钙离子浓度增加，STIMI和ORAI也是参与SOCE的重要组成部分。我们拟探讨Bortezomib对SOCE的作用以及机制。

中文关键词： 肺动脉高压；肺动脉平滑肌细胞；离子通道；蛋白酶体；硼替佐米

英文摘要： Pulmonary hypertension (PH) is a life-threatening disease which included a series of diseases. The increasement of intracellular concentration of Ca2+ of pulmonary artery smooth muscle cells (PASMCs) is the core step in the development of pulmonary artery remodeling which contributes to pulmonary hypertension. Proteasome inhibitor Bortezomib can alleviated pulmonary artery pressure and remodeling in hypoxia and monocrotaline innduced pulmonary hypertension rat model. It is still not known Whether Bortezomib functions by regulating calcium channel. We want to explore effects of Bortezomib on calcium ion channel of pulmonary artery smooth muscle cells in hypoxia induced pulmonary hypertension model. Under hypoxia condition, PPARγ-TRPC1，6 is involved in the increase of Store Operated Calcium Entry(SOCE) which cause the increase of intracellular concentration of Ca2+ of PASMCs. SIMI and ORAI are also involved in SOCE. Thus, we will evaluate effects of Bortezomib on SOCE and PPARγ-TRPC1，6 、SIMI and ORAI in PASMCs in PH model.

英文关键词： Pulmonary hypertension;pulmonary artery smooth muscle cells;ion channel;proteasome;Bortezomib