Ghrelin对大鼠血压和心肌收缩功能的影响

发布时间：2018-07-04 07:08

本文选题：Ghrelin + 血管舒张　；参考：《第四军医大学》2010年硕士论文

【摘要】： Ghrelin是一种可以刺激生长激素分泌的物质,主要由胃肠分泌。Ghrelin受体不仅分布于下丘脑和垂体,参与物质能量代谢和生长激素分泌的调节,也存在于心血管系统。不过,ghrelin对心血管功能的影响目前仍存在争议。通过研究肥胖和消瘦人群血清ghrelin的水平,结合磁共振成像等诊疗手段分析心室的结构和功能,Nicholas等发现血中ghrelin水平与右心室收缩末容积(RVESV)和右心室射血分数(RVEF)等心功能指标存在密切关系,提示其具有正性肌力作用。另一方面,ghrelin可能对心肌也存在直接作用。以往的在体研究发现,ghrelin可以显著提高心搏量、心脏射血分数等心功能指标,提示其对心脏的正性肌力作用。但最近又有研究发现,ghrelin可剂量依赖性地减弱低频刺激下乳头肌心肌细胞的张力。近些年来,ghrelin对外周器官的调节作用,尤其对心血管系统的调节作用受到学者的广泛关注,提示ghrelin对心血管疾病治疗的潜在能力。本文应用人工合成的ghrelin,重点研究其对心血管系统的影响和内在机制,初步探讨其对心血管疾病的潜在治疗价值。主要研究内容: 1.以SD大鼠为观察对象,采用动脉插管的方法,观察ghrelin对整体大鼠血流动力学的影响;; 2.以成年SD大鼠的心肌细胞为观察对象,采用单细胞动态边缘检测系统测定细胞收缩功能的变化; 3.以离体大鼠腹主动脉条为观察对象,采用离体血管灌流,观察ghrelin对离体大鼠腹主动脉的作用; 获得的主要结果如下: 1. Ghrelin(1×10-7~1×10-4 g/kg)可剂量依赖性降低大鼠平均动脉压,对左室内压有一定影响,而对大鼠心率等心血管动力学指标无影响。 2. Ghrelin(1×10-9 ~ 1×10-6 mol/L)可剂量依赖性降低单个心肌细胞收缩最大收缩幅度、最大缩短和复长速率。 3. Ghrelin(1×10-6 mol/L)可舒张离体鼠腹主动脉。以上结果提示: 1.Ghrelin具有负性肌力作用。 2.Ghrelin对动脉有显著的舒张作用,对心脏的负性调节作用及对动脉血管的舒张作用是其降压作用的主要原因。综上所述,本研究证实了ghrelin具有明显的负性肌力作用和心脏抑制作用,同时发现其可舒张腹主动脉。
[Abstract]:Ghrelin is a kind of substance that stimulates the secretion of growth hormone. It is mainly secreted by gastrointestinal tract. Ghrelin receptor is not only distributed in hypothalamus and pituitary, but also involved in the regulation of substance energy metabolism and growth hormone secretion, but also in cardiovascular system. However, the effects of ghrelin on cardiovascular function are still controversial. By studying the serum ghrelin levels of obese and emaciated people, Analysis of ventricular structure and function by magnetic resonance imaging (MRI) showed that the level of ghrelin in blood was closely related to cardiac function such as right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF), which suggested that it had positive inotropic effect. On the other hand, ghrelin may also have a direct effect on myocardium. Previous in vivo studies have shown that ghrelin can significantly increase cardiac function such as cardiac stroke volume and ejection fraction, suggesting its positive inotropic effect on the heart. Recently, however, it has been found that ghrelin can attenuate the tension of papillary myocytes in a dose-dependent manner. In recent years, the regulatory effects of ghrelin on peripheral organs, especially on cardiovascular system, have attracted extensive attention, suggesting the potential ability of ghrelin in the treatment of cardiovascular diseases. In this paper, synthetic ghrelin was used to study the effects of ghrelin on cardiovascular system and its intrinsic mechanism, and to explore the potential therapeutic value of ghrelin on cardiovascular disease. Main research contents: 1. The effect of ghrelin on hemodynamics of the whole rat was observed by arterial catheterization in SD rats. 2. The changes of contractile function of adult SD rat cardiomyocytes were measured by single cell dynamic edge detection system. The effects of ghrelin on isolated rat abdominal aorta were observed by vascular perfusion in vitro. The main results were as follows: 1. Ghrelin (1 脳 10-7 脳 10-4 g/kg) decreased the mean arterial pressure in a dose-dependent manner, and had a certain effect on left ventricular pressure, but had no effect on cardiovascular parameters such as heart rate. 2. Ghrelin (1 脳 10 ~ (-9) ~ 1 脳 10 ~ (-6) mol / L) decreased the maximal contraction amplitude, the maximum shortening and the complex length rate of single cardiomyocytes in a dose-dependent manner. Ghrelin (1 脳 10-6 mol / L) can dilate isolated rat abdominal aorta. These results suggest that: 1. Ghrelin has a negative inotropic effect. 2. Ghrelin has a significant diastolic effect on arteries. The negative regulation of the heart and the vasodilation of the artery are the main causes of its hypotension. In conclusion, this study confirmed that ghrelin has negative inotropic and cardiac inhibitory effects, and found that ghrelin can dilate the abdominal aorta.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R341

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