cAMP及其增多因素對家兔心房ANP分泌的影響
本文關(guān)鍵詞:cAMP及其增多因素對家兔心房ANP分泌的影響 出處:《延邊大學(xué)》2006年碩士論文 論文類型:學(xué)位論文
更多相關(guān)文章: cAMP ANP L型Ca~(2+)通道 心房動力學(xué) 蛋白激酶
【摘要】:心房鈉尿肽(ANP)是由心臟的心房合成和分泌的激素,其主要作用是參與調(diào)節(jié)體液、電解質(zhì)平衡及血壓。而且對機(jī)體的中樞神經(jīng)系統(tǒng)、心血管系統(tǒng)、腎臟以及生殖系統(tǒng)等功能也具有相應(yīng)效應(yīng)。研究表明,ANP分泌與心房動力學(xué)(dynamics)的變化有關(guān),但其機(jī)制不甚清楚。本研究采用跳動家兔心房灌流模型,觀察能夠改變心房動力學(xué)的cAMP及其增多因素對ANP分泌的影響,闡明其作用與Ca~(2+)的相互關(guān)系,探討cAMP對ANP分泌的作用機(jī)制。結(jié)果發(fā)現(xiàn),當(dāng)增加心房跳動頻率(0.8,1.0,1.3,1.6及2.0 Hz)時,在一定范圍內(nèi)隨著心房輸出量和細(xì)胞外液移動量增多的同時ANP分泌和ANP濃度明顯增加。當(dāng)處理cAMP的增多因素時,如異丙腎上腺素(isoprterenol,1.0 nM)、能夠直接激活腺苷酸環(huán)化酶(adenyly cyclase,AC)的forskolin(1.0 μM)或抑制細(xì)胞內(nèi)cAMP降解的磷酸酯酶非選擇性抑制劑IBMX(3-isobutyl-1-methylxanthine,IBMX,1.0 mM)均導(dǎo)致cAMP逸出量及其濃度明顯增多的同時ANP分泌及其濃度明顯受到抑制,并且心房輸出量和房內(nèi)壓明顯增高,而細(xì)胞外液的移動量則稍有變化,但沒有統(tǒng)計學(xué)差異。而且cAMP的增多因素明顯改變了ANP分泌與心房輸出量、ANP分泌與細(xì)胞外液的移動量以及心房輸出量與細(xì)胞外液移動量之間的相互關(guān)系(關(guān)系曲線向右下方移動)。當(dāng)處理能夠透過細(xì)胞膜進(jìn)入細(xì)胞內(nèi)的cAMP類似物8-bromo cAMP(8-bromo adenosine 3’,5’-cyclicmonophosphme,,8-bromo cAMP,0.5 mM)后能也觀察到心房ANP分泌及其濃度明顯受到抑制,而且ANP分泌與心房輸出量、ANP分泌與細(xì)胞外液的移動量以及心房輸出量與細(xì)胞外液移動量的相互關(guān)系曲線也向右下方移動的變化。在forskolin(1.0 μM)存在下處理L-型Ca~(2+)阻斷劑diltiazem(10 μM)時,盡管diltiazem對cAMP生成有所減緩,但仍高于對照組,并且diltiazem沒能改變forskolin對ANP分泌的抑制效應(yīng)。但在蛋白激酶非選擇性抑制劑staurosporine(1.0 μM)存在下,盡管forskolin能促進(jìn)cAMP的生成,但對ANP分泌的抑制效應(yīng)被消失。以上研究結(jié)果提示,細(xì)胞內(nèi)cAMP對ANP分泌具有抑制性調(diào)節(jié)作用,并且其作用是通過蛋白激酶—依賴性的信號轉(zhuǎn)導(dǎo)途徑而實現(xiàn)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.
【學(xué)位授予單位】:延邊大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R33
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相關(guān)博士學(xué)位論文 前2條
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相關(guān)碩士學(xué)位論文 前7條
1 李新華;房室折返心動過速及房室結(jié)折返心動過速病人心鈉素濃度的變化及機(jī)制[D];青島大學(xué);2003年
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3 張瑩;PACAP27對ANP分泌的影響及其機(jī)制研究[D];延邊大學(xué);2007年
4 劉洋;長白山黃芪水提液對心房機(jī)械活動及心房鈉尿肽分泌的影響[D];延邊大學(xué);2008年
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