cAMP及其增多因素对家兔心房ANP分泌的影响

发布时间：2017-12-27 12:02

本文关键词：cAMP及其增多因素对家兔心房ANP分泌的影响　出处：《延边大学》2006年硕士论文　论文类型：学位论文

【摘要】：心房钠尿肽(ANP)是由心脏的心房合成和分泌的激素，其主要作用是参与调节体液、电解质平衡及血压。而且对机体的中枢神经系统、心血管系统、肾脏以及生殖系统等功能也具有相应效应。研究表明，ANP分泌与心房动力学(dynamics)的变化有关，但其机制不甚清楚。本研究采用跳动家兔心房灌流模型，观察能够改变心房动力学的cAMP及其增多因素对ANP分泌的影响，阐明其作用与Ca~(2+)的相互关系，探讨cAMP对ANP分泌的作用机制。结果发现，当增加心房跳动频率(0.8，1.0，1.3，1.6及2.0 Hz)时，在一定范围内随着心房输出量和细胞外液移动量增多的同时ANP分泌和ANP浓度明显增加。当处理cAMP的增多因素时，如异丙肾上腺素(isoprterenol，1.0 nM)、能够直接激活腺苷酸环化酶(adenyly cyclase，AC)的forskolin(1.0 μM)或抑制细胞内cAMP降解的磷酸酯酶非选择性抑制剂IBMX(3-isobutyl-1-methylxanthine，IBMX，1.0 mM)均导致cAMP逸出量及其浓度明显增多的同时ANP分泌及其浓度明显受到抑制，并且心房输出量和房内压明显增高，而细胞外液的移动量则稍有变化，但没有统计学差异。而且cAMP的增多因素明显改变了ANP分泌与心房输出量、ANP分泌与细胞外液的移动量以及心房输出量与细胞外液移动量之间的相互关系(关系曲线向右下方移动)。当处理能够透过细胞膜进入细胞内的cAMP类似物8-bromo cAMP(8-bromo adenosine 3’，5’-cyclicmonophosphme，，8-bromo cAMP，0.5 mM)后能也观察到心房ANP分泌及其浓度明显受到抑制，而且ANP分泌与心房输出量、ANP分泌与细胞外液的移动量以及心房输出量与细胞外液移动量的相互关系曲线也向右下方移动的变化。在forskolin(1.0 μM)存在下处理L-型Ca~(2+)阻断剂diltiazem(10 μM)时，尽管diltiazem对cAMP生成有所减缓，但仍高于对照组，并且diltiazem没能改变forskolin对ANP分泌的抑制效应。但在蛋白激酶非选择性抑制剂staurosporine(1.0 μM)存在下，尽管forskolin能促进cAMP的生成，但对ANP分泌的抑制效应被消失。以上研究结果提示，细胞内cAMP对ANP分泌具有抑制性调节作用，并且其作用是通过蛋白激酶—依赖性的信号转导途径而实现的。
[Abstract]:Atrial natriuretic peptide (ANP) is a hormone synthesized and secreted by the heart's atrium. Its main role is to regulate body fluid, electrolyte balance and blood pressure. It also has the corresponding effects on the functions of the central nervous system, the cardiovascular system, the kidney and the reproductive system. Studies have shown that ANP secretion is associated with changes in atrial dynamics (dynamics), but its mechanism is not very clear. In this study, a rabbit model of atrial perfusion was used to observe the effects of cAMP and its increasing factors on the secretion of ANP, and elucidate the relationship between Ca~ and 2+ and the mechanism of cAMP on ANP secretion. It was found that when the atrial beating frequency increased (0.8, 1, 1.3, 1.6, and 2 Hz), the ANP secretion and ANP concentration increased significantly within a certain range with the increase of atrial output and extracellular fluid mobility. When dealing with the increase of cAMP factors, such as isoproterenol (isoprterenol, 1 nM), can directly activate adenylate cyclase (adenyly cyclase, AC) forskolin (1 M) or inhibition of phosphatase intracellular degradation of cAMP non selective inhibitor of IBMX (3-isobutyl-1-methylxanthine, IBMX, 1 mM) resulted in cAMP escape the amount and concentration increased significantly while ANP secretion and its concentration was significantly inhibited, and atrial output and intra atrial pressure increased significantly, while the amount of movement of extracellular fluid is slightly changed, but the difference was not statistically significant. Moreover, the increasing factors of cAMP significantly changed the relationship between ANP secretion and atrial output, ANP secretion and the movement of extracellular fluid, as well as the relationship between atrial output and extracellular fluid movement. When treatment can penetrate the cell membrane into the cells of the cAMP analogues of 8-bromo cAMP (8-bromo adenosine 3 ', 5' -cyclicmonophosphme, 8-bromo cAMP, 0.5 mM) can also observed atrial ANP secretion and its concentration was significantly inhibited, the relationship between the curve and the secretion of ANP and atrial output, ANP secretion and extracellular fluid movement the output and the atrial extracellular fluid and the amount of change to the right below the mobile mobile. In the presence of forskolin (1 M), when L- Ca~ (2+) blocker diltiazem (10 M M) was processed, diltiazem slowed down cAMP production, but it was still higher than the control group, and diltiazem did not change the inhibition effect of forskolin on the secretion of cAMP. However, in the presence of protein kinase non selective inhibitor staurosporine (1 M), although forskolin can promote cAMP production, the inhibitory effect on ANP secretion is disappeared. These findings suggest that intracellular cAMP plays an inhibitory regulatory role on ANP secretion, and its effect is achieved through protein kinase dependent signal transduction pathway.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R33

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