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作 者:陈爱兰[1] 陈新宇[2] 苏楠[1] 杜丽波[1] 林峰丞 陈学文[1]
机构地区:[1]广州医科大学附属第一医院心血管内科,广东广州510120 [2]广州医科大学病原生物学教研室,广东广州511436
出 处:《广州医科大学学报》2017年第3期5-9,共5页Academic Journal of Guangzhou Medical University
基 金:广东省自然科学基金(2014A030310077);广东省高等学校优秀青年教师培养计划资助项目(YQ2015138);广州市科信局基金(2014Y2-00085)
摘 要:目的:探讨氯沙坦钾对压力超负荷大鼠心肌能量代谢的影响及其机制。方法:将18只Wistar大鼠随机分3组:假手术组(Sham组)、手术组(AAC组)和手术+氯沙坦钾治疗组(AAC+LP组),采用腹主动脉部分缩窄法建立压力超负荷的动物模型,AAC+LP组每天给予氯沙坦钾10 mg/(kg·d),溶于2 m L生理盐水中,Sham组、AAC组给予等体积的生理盐水;8周后,测量全心/体重的比值;颈总动脉插管检测血压;小动物超声测量心脏功能;HE染色测心肌细胞横截面积;采用荧光定量PCR法检测心肌组织GLUT4mRNA表达,试剂盒测定心肌组织ADP/ATP比值。结果:8周后与Sham组相比,AAC组血压、全心/体重比值、左室壁厚度增加、心肌细胞横截面积增大,心脏功能下降,心肌ADP/ATP比值增加、GLUT4表达下降;AAC+LP组血压、全心/体重比值、左室壁厚度、心脏功能改善,ADP/ATP比值下降、GLUT4表达上升。结论:氯沙坦钾改善压力负荷心肌收缩、舒张功能的作用,其机制可能与其降低血压的同时增加肥厚心肌GLUT4的表达,改善心肌的能量代谢有关。Objective:To investigate the effect of Losartan potassium on ventricular remodeling in rats with pressure overload and its mechanism. Methods:Eighteen Wistar rats were randomly divided into 3 groups:the sham operation group ( Sham group ) , abdominal aortic constriction group ( AAC group ) and AAC+Losartan Potassium treatment group ( AAC+LP group) . The animal model of pressure overload was established by partial constriction of abdominal aorta. The AAC+LP group was given 10 mg/( kg?d) Losartan potassium daily,which was dissolved in 2 mL normal saline. The Sham group and AAC group were given equal volume of normal saline. At 8 weeks,the ratio of heart weight/body weight ( HW/BW) was measured;the blood pressure was examined by common carotid artery intubation; the cardiac function was measured by small animal ultrasound; the cross-sectional area of myocardial cells was determined by HE staining;the expression of GLUT4 mRNA in myocardium was determined by fluorescence quantitative PCR; and the ADP/ATP ratio was measured by the assay kit. Results:At 8 weeks, compared with the Sham group, the blood pressure, HW/BW ratio, left ventricular wall thickness,myocardial cell cross-sectional area and ADP/ATP ratio increased, whereas the cardiac function and GLUT4 expression decreased in the AAC group; the blood pressure, HW/BW ratio, left ventricular wall thickness, and cardiac function were improved, the ADP/ATP ratio decreased, and the GLUT4 expression increased in the AAC+LP group. Conclusion:Losartan potassium can improve systolic and diastolic function of pressure-overloaded myocardium. Its mechanism may be related to the decrease of blood pressure with the increase of GLUT4 expression in hypertrophic myocardium, and the improvement of myocardial energy metabolism.
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