CD-NP对慢性心力衰竭大鼠模型利钠肽系统的影响

发布时间：2018-07-06 10:19

本文选题：CD-NP + 慢性心力衰竭　；参考：《延边大学》2017年硕士论文

【摘要】：目的:CD-NP是一种新型的排钠性利尿剂,对于慢性心衰的疗效及作用机制尚不明确。本课题拟在大鼠心肌梗死所致慢性心衰模型中观察CD-NP对慢性心衰的疗效,以及对利钠肽系统的影响,阐明CD-NP的作用机制。方法:本研究通过冠状动脉-前降支结扎法制备心肌梗死后慢性心衰大鼠模型,测定模型中大鼠体重、平均动脉压(MAP),心脏、左室与室间隔重量以及心脏、左室、室间隔与体重比值;采用超声心动图测定模型中大鼠舒张末期及收缩末期左室前壁厚度、左室后壁厚度、左室内径和左室射血分数、左室短轴缩短率。通过股静脉给药方式输注CD-NP后,与安慰剂组对照,再次测定上述指标。给药后牺牲各组大鼠,收集血浆及血清,通过放射性免疫分析(Radioimmunoassay,RIA)及酶联免疫吸附测定(Enzyme linked immunosorbent assay,ELISA)测定 ANP、BNP、NT-proBNP;收集新鲜心脏组织,经福尔马林固定、石蜡包埋等处理后制备冠状切片,作相应染色后观察心脏组织病理学变化;采用免疫组织化学染色法(Immunohistochemistry)测定心脏利钠肽受体(Natriuretic pepitide receptor,NPR)表达是否增强,采用实时聚合酶链式反应(Polymerase chain reaction,PCR)技术测定利钠肽系统相关物质的mRNA表达。结果:在冠状动脉-前降支结扎法制备的大鼠慢性心衰模型中体重显著降低,心脏、左室与室间隔重量,心脏、左室、室间隔与体重比值均显著升高,心率略升高,但无统计学意义,平均动脉压无明显改变。CD-NP治疗(均经股静脉给药方式以10ng-1kg-1min速度,连续5天每日3小时输注)在假手术组中对体重、心脏、左室与室间隔重量以及慢性心衰模型中对体重、心脏、左室与室间隔重量、心脏、左室、室间隔与体重比值变化均无明显改善,且对心率、平均动脉压无明显影响。与假手术组相比,在冠状动脉-前降支结扎法制备的大鼠慢性心衰模型中舒张末期及收缩末期左室前壁厚度、左室内径和左室射血分数、左室短轴缩短率均显著降低,舒张末期及收缩末期左室后壁厚度显著升高。CD-NP治疗在假手术组中对舒张末期及收缩末期左室前壁厚度、左室后壁厚度、左室内径和左室射血分数、左室短轴缩短率均无明显改变。在冠状动脉-前降支结扎法制备的大鼠慢性心衰模型中显著增加了舒张末期及收缩末期左室前壁厚度、左室内径,对左室射血分数、左室短轴缩短率、舒张末期和收缩末期左室后壁厚度无明显改变。与假手术组相比,在冠状动脉-前降支结扎法制备的大鼠慢性心衰模型心脏组织中可见明显的心肌纤维化和心肌细胞的损伤。CD-NP治疗在冠状动脉结扎法制备的大鼠慢性心衰模型中心肌纤维化和心肌细胞的损伤显著降低。与假手术组相比,在冠状动脉结扎法制备的大鼠慢性心衰模型中ANP、BNP、NT-proBNP水平显著升高。CD-NP治疗在假手术组中对ANP、BNP、NT-proBNP水平及均无明显改变。在冠状动脉结扎法制备的大鼠慢性心衰模型中ANP、BNP、NT-proBNP水平显著降低。与假手术组相比,在冠状动脉结扎法制备的大鼠慢性心衰模型中左心室ANP、BNP、NPR-C的mRNA表达显著升高,NPR-A的mRNA表达显著降低,NPR-B的mRNA表达无明显改变。CD-NP治疗在假手术组中对左心室ANP、BNP、NPR-A、NPR-B及NPR-C的mRNA表达均无明显改变;在冠状动脉结扎法制备的大鼠慢性心衰模型中左心室ANP、BNP、NPR-C的mRNA表达显著减少,NPR-A的mRNA表达增加,对NPR-B的mRNA表达无明显改变。结论:冠状动脉-前降支结扎法造成心肌梗死后大鼠慢性心衰模型存在心功能异常;心肌纤维化及心肌损伤,说明冠状动脉-前降支结扎法造成心肌梗死后大鼠慢性心衰模型成功建立。左心室利钠肽系统激活参与了心肌梗死后慢性心衰发病机制。CD-NP虽不能改变冠状动脉-前降支结扎法造成心肌梗死后慢性心衰模型大鼠体重、心脏重量等,但对心率及血压无明显副作用。CD-NP可增加舒张末期及收缩末期左室前壁厚度,减少左室内径;降低心肌纤维化及心肌细胞损伤程度;抑制左室利钠肽系统,产生生物学效应,从而有助于改善心功能异常。
[Abstract]:Objective: CD-NP is a new type of sodium diuretic, which is not clear for the effect and mechanism of chronic heart failure. This subject is to observe the effect of CD-NP on chronic heart failure and the effect on the system of natriuretic peptide in the model of chronic heart failure caused by myocardial infarction in rats, and to clarify the mechanism of action of CD-NP. The rat model of chronic heart failure after myocardial infarction was prepared by ligation of the descending branch. The weight of rats, the mean arterial pressure (MAP), the heart, the left ventricular septum weight and the ratio of the heart, left ventricle, interventricular septum to body weight were measured. The thickness of left ventricular anterior wall, left ventricular posterior wall thickness, left ventricular wall thickness, left ventricle, left ventricular wall thickness, left ventricle, left ventricle, left ventricle, left ventricle, left ventricle, left ventricle, left ventricle, and left ventricle were measured by echocardiography. Internal and left ventricular ejection fraction, short axis shortening of left ventricle. After infusion of CD-NP in the femoral vein, the above indexes were measured again with the placebo group. After the administration, the rats were sacrificed and the plasma and serum were collected by radioimmunoassay (Radioimmunoassay, RIA) and enzyme linked immunosorbent assay (Enzyme linked immunosorbent assay). ELISA) determination of ANP, BNP, NT-proBNP; collected fresh cardiac tissue, after formalin fixation, paraffin embedding and other treatments to prepare coronal section, observe the pathological changes of heart tissue after corresponding staining, and use immunohistochemical staining (Immunohistochemistry) to determine the expression of Natriuretic pepitide receptor, NPR expression. Polymerase chain reaction (PCR) technique was used to determine the mRNA expression of the related substances in the natriuretic peptide system. Results: the weight of the heart, the left ventricle and interventricular septum, the heart, the left ventricle, the ventricular septum, and the weight ratio were significantly decreased in the rat model of chronic heart failure prepared by the coronary artery anterior descending ligation. A significant increase in heart rate was slightly higher, but there was no statistical significance. The mean arterial pressure was not significantly altered by.CD-NP treatment (both at 10ng-1kg-1min rate, 5 days after the femoral vein administration), weight, heart, left ventricular and ventricular septal weight, and chronic heart failure in the sham operation group, and weight, heart, left ventricular and ventricular septum weight in the chronic heart failure model. Volume, heart, left ventricle, ventricular septum and weight ratio did not improve significantly, and had no significant influence on heart rate and mean arterial pressure. Compared with the sham group, the end diastolic and late systolic left ventricular anterior wall thickness, left ventricular diameter and left ventricular ejection fraction, and left ventricular short axis contraction in the rat model of coronary artery anterior descending ligation were compared with the sham operation group. The short rate was significantly reduced, and the thickness of the left ventricular posterior wall was significantly increased at the end of diastolic and end systolic stage. The thickness of the left ventricle, left ventricular posterior wall thickness, left ventricular diameter and left ventricular ejection fraction, and the short axis shortening rate of left ventricle were not changed significantly in the sham operation group with.CD-NP treatment in the sham operation group. In the rat model of chronic heart failure, the end diastolic and end systolic anterior wall thickness was significantly increased, left ventricular diameter, left ventricular ejection fraction, short axis shortening, late diastolic and late systolic left ventricular posterior wall thickness unchanged. Compared with the sham group, the rat model of chronic heart failure was prepared by ligation of the coronary artery anterior descending branch. Significant myocardial fibrosis and myocardial damage were seen in the tissue.CD-NP treatment in the rat model of chronic heart failure prepared by coronary artery ligation, the central muscle fibrosis and myocardial damage decreased significantly. Compared with the sham group, the level of ANP, BNP, and NT-proBNP in the rat model of slow heart failure prepared by coronary artery ligation was significant. The levels of ANP, BNP, and NT-proBNP were not significantly changed in the sham operation group. The levels of ANP, BNP and NT-proBNP in the rat model of chronic heart failure were significantly reduced in the rat model of coronary artery ligation. Compared with the sham group, the mRNA expression of the left ventricular ANP, BNP, NPR-C in the rat model of coronary artery ligation was made in the rat model of coronary artery ligation. The expression of mRNA in NPR-A was significantly decreased, and the expression of mRNA in NPR-B had no significant changes in the ANP, BNP, NPR-A, NPR-B and NPR-C mRNA expression in the left ventricular group in the sham operation group, and the expression of the left ventricular ANP in the rat model of coronary artery ligation was significantly reduced. There was no obvious change in expression of mRNA in NPR-B. Conclusion: coronary artery anterior descending branch ligation has caused abnormal cardiac function in the rat model of chronic heart failure after myocardial infarction; myocardial fibrosis and myocardial injury. It is suggested that the coronary artery anterior descending ligation in the rat model of chronic heart failure after myocardial infarction successfully established the left ventricular natriuretic peptide. The system activation participates in the pathogenesis of chronic heart failure after myocardial infarction.CD-NP can not change the weight and heart weight of the rat model of chronic heart failure after the coronary artery anterior descending branch ligation, but there is no obvious side effect on heart rate and blood pressure,.CD-NP can increase the thickness of the left ventricular anterior wall at the end of diastolic stage and the end systole, and reduce the left ventricular diameter. It can reduce the degree of myocardial fibrosis and myocardial cell damage, inhibit the left ventricular natriuretic peptide system, and produce biological effects, which is helpful to improve cardiac dysfunction.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.6;R-332

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