气体信号分子硫化氢对心肌肥厚的作用研究

发布时间：2018-01-19 05:17

本文关键词： 气体信号分子硫化氢心肌厚的作用研究　出处：《中国协和医科大学》2006年硕士论文　论文类型：学位论文

【摘要】：心肌肥厚为心脏对几乎所有心脏病变因素的一种适应性反应，但长期的心肌肥厚最终将导致失代偿，而发生心肌缺血、心力衰竭和猝死，是心血管病患者死亡的重要原因之一。临床上，各种原因引起的心肌肥厚均存在心脏基质的改变，即心成纤维细胞(CFs)增殖、间质纤维化。心肌肥厚时，由于交感神经兴奋性增高而导致CFs细胞旁分泌、自分泌增强，进一步促进CFs细胞增殖、分泌胶原以及其他间质成分。CFs细胞的数量和分泌胶原的能力影响着心脏的结构和硬度。硫化氢(hydrogen sulfide，H_2S)长期被认为是一种有毒的气体，上个世纪90年代中期开始，人们发现含硫氨基酸代谢所产生的H_2S对神经系统，特别是海马的功能具有调节作用，随后的研究发现H_2S可舒张血管平滑肌，降低肺动脉高压和高血压大鼠的血压。H_2S除了对神经系统、心血管系统中具有重要的调节作用外，大量研究还发现H_2S在消化、泌尿、血液等系统中都起着重要作用。H_2S可能具有与一氧化氮(NO)、一氧化碳(CO)相似的生物学特性，而有望成为第三个气体信号分子。迄今，有关H_2S在心血管系统中的作用主要集中在对血管作用方面的研究，而其对心脏的直接作用罕见报道，仅限于内源性H_2S可能通过开放心肌K_(ATP)通道而抑制大鼠离体心脏左心室的收缩功能；内源性H_2S可能通过激活PKC、开放心肌K_(ATP)通道以及促进NO释放等发挥对离体培养的大鼠心室肌细胞缺血预适应的保护作用。目前，，已知催化生成内源性H_2S的酶属于5’-磷酸吡多醛依赖酶，包括胱硫酶β合成酶(cystathionine β-synthase，CBS)和胱硫酶丫裂解酶(cystathionine γ-lyase，CSE)。心肌组织中特异性地存在大量CSE，而几乎没有CBS存在。上述均提示：心脏中H_2S／CSE体系可能对心脏的功能具有重要作用。但迄今为止，尚无有关H_2S对心肌肥厚作用方面的报道。
[Abstract]:Myocardial hypertrophy is an adaptive response of the heart to almost all factors of heart disease, but long-term cardiac hypertrophy will eventually lead to decompensation, with myocardial ischemia, heart failure and sudden death. It is one of the important causes of death in patients with cardiovascular disease. In clinic, cardiac hypertrophy caused by various causes has cardiac matrix changes, that is, cardiac fibroblast CFS) proliferation, interstitial fibrosis, myocardial hypertrophy. Increased sympathetic excitability leads to paracrine and autocrine of CFs cells, which further promotes the proliferation of CFs cells. The number and ability of collagen secreting collagen and other interstitial components. Hydrogen sulfide hydrogen sulfide H2S) has long been considered as a toxic gas, beginning on the middle of -10s. It has been found that the H2S produced by the metabolism of sulfur-containing amino acids can regulate the function of the nervous system, especially the hippocampus. Later studies have found that H2S can relax vascular smooth muscle. In addition to reducing blood pressure. H2S plays an important role in regulating nervous system and cardiovascular system in rats with pulmonary hypertension and hypertension, a large number of studies also found that H2s in digestion, urinary. H2S may have biological characteristics similar to that of nitric oxide (no) and carbon monoxide (CO), and may become the third gas signaling molecule. The role of H2S in the cardiovascular system is mainly focused on the study of vascular effects, and its direct effect on the heart is rarely reported. Only endogenous H2S may inhibit the contractile function of left ventricle in isolated rat heart by opening up the myocardial K _ (+) T _ (+) T _ (29) channel. Endogenous H2S may play a protective role on ischemic preconditioning of isolated rat ventricular myocytes by activating PKC, opening up myocardial K _ (T _ 1) -ATPase channel and promoting the release of nitric oxide (no). It is known that the enzymes that catalyze the formation of endogenous H2S belong to the 5-pyridine phosphate polyaldehyde dependent enzyme, including cystathionine 尾 -synthase, cystathionine 尾 -synthase, including cystathionine 尾 -synthase. There is a large number of CSE in cardiac muscle tissue, and cystathionine 纬 -lyase (CSE) and cystathionine 纬 lyase (cystathionine 纬 -lyase). These results suggest that the H2s / CSE system in the heart may play an important role in the function of the heart. There is no report on the effect of H _ 2S on myocardial hypertrophy.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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