發(fā)布時間：2018-07-06 10:19

  本文選題：CD-NP + 慢性心力衰竭　； 參考：《延邊大學(xué)》2017年碩士論文

【摘要】：目的:CD-NP是一種新型的排鈉性利尿劑,對于慢性心衰的療效及作用機制尚不明確。本課題擬在大鼠心肌梗死所致慢性心衰模型中觀察CD-NP對慢性心衰的療效,以及對利鈉肽系統(tǒng)的影響,闡明CD-NP的作用機制。方法:本研究通過冠狀動脈-前降支結(jié)扎法制備心肌梗死后慢性心衰大鼠模型,測定模型中大鼠體重、平均動脈壓(MAP),心臟、左室與室間隔重量以及心臟、左室、室間隔與體重比值;采用超聲心動圖測定模型中大鼠舒張末期及收縮末期左室前壁厚度、左室后壁厚度、左室內(nèi)徑和左室射血分數(shù)、左室短軸縮短率。通過股靜脈給藥方式輸注CD-NP后,與安慰劑組對照,再次測定上述指標。給藥后犧牲各組大鼠,收集血漿及血清,通過放射性免疫分析(Radioimmunoassay,RIA)及酶聯(lián)免疫吸附測定(Enzyme linked immunosorbent assay,ELISA)測定 ANP、BNP、NT-proBNP;收集新鮮心臟組織,經(jīng)福爾馬林固定、石蠟包埋等處理后制備冠狀切片,作相應(yīng)染色后觀察心臟組織病理學(xué)變化;采用免疫組織化學(xué)染色法(Immunohistochemistry)測定心臟利鈉肽受體(Natriuretic pepitide receptor,NPR)表達是否增強,采用實時聚合酶鏈式反應(yīng)(Polymerase chain reaction,PCR)技術(shù)測定利鈉肽系統(tǒng)相關(guān)物質(zhì)的mRNA表達。結(jié)果:在冠狀動脈-前降支結(jié)扎法制備的大鼠慢性心衰模型中體重顯著降低,心臟、左室與室間隔重量,心臟、左室、室間隔與體重比值均顯著升高,心率略升高,但無統(tǒng)計學(xué)意義,平均動脈壓無明顯改變。CD-NP治療(均經(jīng)股靜脈給藥方式以10ng-1kg-1min速度,連續(xù)5天每日3小時輸注)在假手術(shù)組中對體重、心臟、左室與室間隔重量以及慢性心衰模型中對體重、心臟、左室與室間隔重量、心臟、左室、室間隔與體重比值變化均無明顯改善,且對心率、平均動脈壓無明顯影響。與假手術(shù)組相比,在冠狀動脈-前降支結(jié)扎法制備的大鼠慢性心衰模型中舒張末期及收縮末期左室前壁厚度、左室內(nèi)徑和左室射血分數(shù)、左室短軸縮短率均顯著降低,舒張末期及收縮末期左室后壁厚度顯著升高。CD-NP治療在假手術(shù)組中對舒張末期及收縮末期左室前壁厚度、左室后壁厚度、左室內(nèi)徑和左室射血分數(shù)、左室短軸縮短率均無明顯改變。在冠狀動脈-前降支結(jié)扎法制備的大鼠慢性心衰模型中顯著增加了舒張末期及收縮末期左室前壁厚度、左室內(nèi)徑,對左室射血分數(shù)、左室短軸縮短率、舒張末期和收縮末期左室后壁厚度無明顯改變。與假手術(shù)組相比,在冠狀動脈-前降支結(jié)扎法制備的大鼠慢性心衰模型心臟組織中可見明顯的心肌纖維化和心肌細胞的損傷。CD-NP治療在冠狀動脈結(jié)扎法制備的大鼠慢性心衰模型中心肌纖維化和心肌細胞的損傷顯著降低。與假手術(shù)組相比,在冠狀動脈結(jié)扎法制備的大鼠慢性心衰模型中ANP、BNP、NT-proBNP水平顯著升高。CD-NP治療在假手術(shù)組中對ANP、BNP、NT-proBNP水平及均無明顯改變。在冠狀動脈結(jié)扎法制備的大鼠慢性心衰模型中ANP、BNP、NT-proBNP水平顯著降低。與假手術(shù)組相比,在冠狀動脈結(jié)扎法制備的大鼠慢性心衰模型中左心室ANP、BNP、NPR-C的mRNA表達顯著升高,NPR-A的mRNA表達顯著降低,NPR-B的mRNA表達無明顯改變。CD-NP治療在假手術(shù)組中對左心室ANP、BNP、NPR-A、NPR-B及NPR-C的mRNA表達均無明顯改變;在冠狀動脈結(jié)扎法制備的大鼠慢性心衰模型中左心室ANP、BNP、NPR-C的mRNA表達顯著減少,NPR-A的mRNA表達增加,對NPR-B的mRNA表達無明顯改變。結(jié)論:冠狀動脈-前降支結(jié)扎法造成心肌梗死后大鼠慢性心衰模型存在心功能異常;心肌纖維化及心肌損傷,說明冠狀動脈-前降支結(jié)扎法造成心肌梗死后大鼠慢性心衰模型成功建立。左心室利鈉肽系統(tǒng)激活參與了心肌梗死后慢性心衰發(fā)病機制。CD-NP雖不能改變冠狀動脈-前降支結(jié)扎法造成心肌梗死后慢性心衰模型大鼠體重、心臟重量等,但對心率及血壓無明顯副作用。CD-NP可增加舒張末期及收縮末期左室前壁厚度,減少左室內(nèi)徑;降低心肌纖維化及心肌細胞損傷程度;抑制左室利鈉肽系統(tǒng),產(chǎn)生生物學(xué)效應(yīng),從而有助于改善心功能異常。
[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.
【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】：2017
【分類號】：R541.6;R-332

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