【作者】 孙晶；

【导师】 余再新；

【作者基本信息】 中南大学 ， 临床医学， 2023， 硕士

【摘要】 背景:肺动脉高压是以肺动脉压力持续升高为特点的进行性肺血管疾病,最终可能导致右心衰竭甚至死亡。细胞衰老是以细胞周期不可逆阻滞为特点的一种细胞状态,其也是体内炎症因子的重要来源。Galectin-3是β-半乳糖凝集素家族的一员,研究已经表明,其在炎症调节中发挥了重要作用。研究目的:本文主要探究细胞衰老在肺动脉高压中的作用及其是否受到Galectin-3的调节。研究方法:MCT及低氧建立肺动脉高压动物模型,检测其造模效果和细胞衰老标志物的水平;TGF-β建立肺动脉高压的成纤维细胞模型,检测其衰老标志物水平;过氧化氢建立细胞衰老的成纤维细胞模型,检测其纤维化标志物水平;通过基因鼠和si RNA检测体内外Gal-3的敲减对细胞衰老的影响。研究结果:肺动脉高压的动物模型和成纤维细胞模型中,细胞衰老标志物的表达水平明显升高。细胞衰老参与肺动脉高压的病理过程可能与衰老细胞分泌的物质参与了外膜纤维化过程有关。细胞衰老过程参与肺动脉高压的过程可能受到Galectin-3的调节。结论:研究主要发现细胞衰老可能主要通过衰老相关的分泌表型影响肺动脉高压相关的纤维化过程而参与肺动脉高压,这一过程可能受到Galectin-3的调节。图7幅,表0个,参考文献156篇更多还原

【Abstract】 Background: Pulmonary hypertension is a progressive pulmonary vascular disease characterized by elevated pulmonary artery pressure that can eventually lead to right heart failure and death.Galectin-3 is a member of the beta-galactolectin family,which has been shown to play an important role in inflammation regulation.Cell senescence is a cellular state characterized by irreversible arrest of the cell cycle,which is also an important source of inflammatory factors in vivo.Objective: To investigate the role of cellular senescence in pulmonary hypertension and whether it is regulated by Galectin-3.Results: In the animal model of pulmonary hypertension,the expression level of cell senescence markers was significantly increased.The levels of aging markers were also significantly elevated in pulmonary arterial hypertension fibroblast models.Galectin-3 knockdown has been shown to improve the phenotype of pulmonary hypertension by reducing the level of cell senescence in vitro and in vivo.The involvement of cellular senescence in the pathological process of pulmonary hypertension may be related to the involvement of substances secreted by senescent cells in the process of outer membrane fibrosis.Conclusion: Galectin-3 may be involved in the pathological process of pulmonary hypertension by regulating the level of cell senescence.更多还原