【作者】 董明清；

【导师】 朱妙章； 冯华松；

【作者基本信息】 第四军医大学 ， 生理学， 2000， 博士

【摘要】 肺动脉平滑肌细胞(pulmonary artery smooth muscle cell，PASMC)异常增殖是肺动脉高压发病的中心环节，也是其重要的病理改变之一，研究其调控机制对于肺动脉高压的防治具有指导作用。PASMC异常增殖是细胞增殖正调控因子(促增殖因子)和负调控因子(抑增殖因子)失去平衡的结果。钠尿肽家族中的心房钠尿肽(atrial natriuretic peptide，ANP)、脑钠尿肽(brain natriuretic peptide，BNP)和C-型钠尿肽(c-type natriuretic peptide，CNP)具有抑制血管平滑肌细胞、心成纤维细胞、心肌细胞等多种细胞增殖的作用。血管钠肽(vasonatrin peptide，VNP)是人工合成的钠尿肽家族的新成员，是CNP和ANP的嵌合体，具有与ANP、CNP类似的利钠利尿和扩血管效应，但VNP能否抑制细胞增殖目前尚不清楚。 钠尿肽受体(natriuretic peptide receptor，NPR)有A、B、C三个亚型，其中A受体(NPR-A)和B受体(NPR-B)是鸟苷酸环化酶偶联受体，钠尿肽与A、B受体结合后，激活受体的鸟苷酸环化酶活性，通过升高细胞内cGMP发挥生理效应；C受体(NPR-C)为非偶联受体，主要介导钠尿肽的清除。正常情况下，三种受体在体内均广泛分布，但不同组织中分布有很大差异，而且在不同病理条件下钠尿肽受体数目还可发生上调和下调，提示钠尿肽家族对不同组织器官生理性调控作用的差异，并参与各种病理过程的调节。 研究内容：1)以离体培养的大鼠PASMC为研究对象，采用细胞总蛋白含量测定和MTT比色试验，观察了VNP、CNP及ANP对胎牛血清、去甲肾上腺素(NE)及蛋白激酶C(PKC)激动剂佛波醇酯(PMA)刺激的大鼠PASMC增殖的影响，以及三种钠尿肽对PASMC胞内第二信使cGMP、cAMP水平的影响：2)从大鼠新鲜肺组织中提取总RNA，应用反转录、PCR、更多还原

【Abstract】 The abnormal proliferation of pulmonary artery smooth muscle cell(PASMC) is the main mechanism and pathological changes in pulmonary artery hypertension (PAH) . To study the regulation mechanism of PASMC proliferation is very important for the prevention and therapy of PAH. The abnormal proliferation of PASMC is the result of imbalance between the positive and negative regulator. It is known that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) can inhibit the proliferation of vascular smooth cell, heart fibroblast cell and cardiac myocyte besides their diuresis, natriuresis and vasodilating action. Vasonatrin peptide(VNP), which is man synthesized , is a chimera of CNP and ANP. VNP has the similar diuresis, natriuresis and vasodilating action to ANP and CNP However, whether VNP has effects on cell proliferation is not clear.There are three subtypes in natriuretic peptide receptors (NPR): natriuretic peptide receptor-A (NPR-A). natriuretic peptide receptor-B (NPR-B) and natriuretic peptide receptor-C (NPR-C) . NPR-A and NPR-B are particulate guanylate cyclase (GC) - coupled receptor. After NPs binding to NPR-A or NPR-B. GC activity of NPR is activated, which catalysed GTP to cGMP. The elevated cGMP. as a second message, mediates the NPs’ effects. NPR-C, a clearance receptor, is not coupled to GC and mediates the degradation of NPs. NPR are widely but differently distributed in most tissues and can be up- or down- regulated in many pathological process, which indicate that they have different effects on different tissue and take part in the regulation of these pathological process.更多还原