高糖影响肺动脉平滑肌细胞收缩增殖的作用及机制

Hyperglycemia is important for the development of COPD-related pulmonary hypertension (PH), but its specific role and mechanism remain incompletely understood. Increasing tension and remodeling of pulmonary vasculature is an important cause of PH, the main cause of the change are the increase of expression of transient receptor potential canonical channel (TRPC) and intracellular calcium ion concentration in the pulmonary artery smooth muscle cells (PASMCs). Studies have found hyperglycemia can increase intracellular ROS, NOX4 and PPARγ. NOX4, PPARγ can regulate TRPC expression and intracellular calcium concentration. This project intends to focus on PASMCs cultured in normoxic and hypoxic conditions and explore:1. The effects of High glucose on contraction, proliferation and migration of PASMCs; 2.Mechanism: high glucose-NOX4-PPARγ–TRPC-SOCE/ROCE-intracellular [Ca2+]i-proliferation/migration /contraction; 3.Rosiglitazone and/or low sugar diet improves high glucose effect on PASMC. The above work can explain the effect and mechanism of high glucose on COPD-related PH, and provide new ideas for early prevention COPD develop to PH.

高血糖在COPD相关肺动脉高压（PH）的发生发展中具有重要意义，但其具体作用和机制并不明确。肺血管张力的持续增加及重塑是PH的重要病因，肺动脉平滑肌细胞内瞬时受体电位通道(TRPC)增加及其介导的胞内钙离子浓度升高在这两种病理生理改变中发挥核心作用。研究证实高血糖能上调细胞内ROS水平与NOX4、PPARγ表达；NOX4、PPARγ能调节TRPC的表达及细胞内钙离子浓度。本课题拟以PASMCs作为研究靶标，在常氧和缺氧条件下深入研究：1、高糖对PASMCs的收缩、增殖以及迁移功能的影响。2、高糖对PASMCs的作用途径：高糖- NOX4 - PPARγ- TRPC - SOCE/ROCE - 细胞内基础[Ca2+]i - PASMCs增殖/迁移/收缩。3、罗格列酮和/或低糖饮食对高糖作用的改善。以上研究可说明高血糖在COPD相关PH中的作用及机制，为及早防治COPD发展为PH提供新思路。