p53在慢性低压低氧性肺动脉高压形成中的作用

发布时间：2018-05-02 18:25

本文选题：低氧 + 肺动脉高压　；参考：《第四军医大学》2006年硕士论文

【摘要】：肺动脉高压(pulmonary arterial hypertension，PAH)是由多种原因引起的肺部血液循环动力学的功能紊乱，以肺血管阻力进行性增加为临床特征的一组疾病，也是肺循环中最严重，具有最大潜在危险性的慢性疾病，可导致肺源性心脏病，右心衰竭，引起过早死亡。已有的研究表明低氧是引起肺动脉高压的重要原因之一。低氧所致的PAH的发病过程包括：肺部血管收缩、肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells，PASMCs)肥大和增生及肺部血管的重建。目前研究认为，，PASMCs增殖和凋亡的失衡是导致PASMCs增殖累积和肺部血管壁重建的重要因素之一。因此，抑制PASMCs过度增殖，诱导其凋亡可以作为治疗和控制PAH的有效方法。肿瘤抑制基因p53在诱导细胞凋亡中具有一定作用。它是一种多效性的转录因子，在特定条件下具有决定细胞命运的重要作用：一方面是抑制细胞分裂，让其停留在细胞周期的G_1期；另一方面是促使细胞凋亡。p53基因有野生型(wild-type 53，wtp53)和突变型(mutant-type 53，mtp53)两种。wtp53为抑癌基因，对细胞分裂和增殖起负调节作用，还能启动细胞的程序性死亡过程，防止细胞恶性转化。mtp53抑癌功能丧失，失去对细胞异常增殖的抑制作用，它通过正信号调节作用，促进细胞进入增生周期，促进细胞
[Abstract]:Pulmonary arterial hypertensionPAH (PAHs) is a group of diseases characterized by progressive increase of pulmonary vascular resistance, which is caused by various causes and is the most serious of pulmonary circulation. Chronic diseases with the greatest potential risk can lead to pulmonary heart disease, right heart failure, and premature death. Studies have shown that hypoxia is one of the important causes of pulmonary hypertension. The pathogenesis of hypoxic PAH includes pulmonary vasoconstriction and pulmonary arterial smooth muscle. PASMCs) hypertrophy and proliferation and pulmonary vascular remodeling. It is suggested that the imbalance between proliferation and apoptosis of PASMCs is one of the important factors leading to the accumulation of PASMCs proliferation and the remodeling of pulmonary vascular wall. Therefore, inhibiting the excessive proliferation of PASMCs and inducing its apoptosis may be an effective method for the treatment and control of PAH. Tumor suppressor gene p53 plays an important role in inducing apoptosis. It is a multifunctional transcription factor, which plays an important role in determining the fate of cells under certain conditions: on the one hand, it inhibits cell division and keeps it in the GSP 1 phase of cell cycle; On the other hand, there are wild type wild-type 53 (wtp53) and mutant mutant-type 53 (mtp53). Wtp53 is a tumor suppressor gene, which plays a negative role in cell division and proliferation, and can initiate the programmed cell death process. It can prevent the cell malignant transformation. Mtp53 from losing the function of inhibiting the cell proliferation. It can promote the cell into the proliferative cycle and promote the cell through the positive signal regulation.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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