CAJ | 학술논문

目的探讨血管紧张素-(1-7)[Ang-(1-7)]对腹主动脉缩窄所诱导的大鼠心肌肥厚和纤维化的影响.方法对8周龄雄性SD大鼠行腹主动脉缩窄术并随机分为假手术组、模型对照组和Ang-(1-7)治疗组,对1d后仍存活者皮下植入微量泵持续静脉输注Ang-(1-7)或生理盐水,Ang-(1-7)组(n=14)输注Ang-(1-7)(25μg·kg-1·h-1),假手术组(n=15)及模型对照组(n=12)则输注等量的生理盐水,4周后检测血流动力学参数、血浆和心肌AngⅡ浓度、左心室重量指数、心肌细胞横径和心肌胶原容积分数.结果(1)模型对照组动脉收缩压、舒张压、心率、左室收缩压(LVSP)、左心室舒张末压、左室内压最大上升速率(+dp/dtmax)均明显高于假手术组(P均＜0.01),左室内压最大下降速率(-dp/dtmax)低于假手术组(P＜0.01).与模型对照组比较,Ang-(1-7)治疗组LVDEP显著减低(P＜0.05),-dp/dtmax升高(P＜0.05),而收缩压、舒张压、心率、LVSP及+dp/dtmax在两组间无明显差异.(2)在腹主动脉缩窄术后4周,模型对照组左心室质量、左心室质量指数及心肌细胞横径明显高于假手术组(P＜0.01),Ang-(1-7)治疗组上述指标虽高于假手术组,但均明显低于模型对照组(P＜0.05).(3)Ang-(1-7)治疗组心肌中小血管周围及心肌间质中胶原沉积虽多于假手术组,但明显少于模型对照组(P＜0.05).(4)与假手术组比较,模型对照组和Ang-(1-7)治疗组心肌中AngⅡ浓度均明显增高(P＜0.01),但模型对照组和Ang-(1-7)治疗组之间无显著差异(P＞0.05);3组间血浆AngⅡ水平无明显差异(P＞0.05).结论长期静脉输注Ang(1-7)对腹主动脉缩窄引起的动脉压和心肌血管紧张素Ⅱ水平的升高无影响,但使心肌肥厚和纤维化程度显著减轻,并保护受损的心功能.
목적탐토혈관긴장소-(1-7)[Ang-(1-7)]대복주동맥축착소유도적대서심기비후화섬유화적영향.방법대8주령웅성SD대서행복주동맥축착술병수궤분위가수술조、모형대조조화Ang-(1-7)치료조,대1d후잉존활자피하식입미량빙지속정맥수주Ang-(1-7)혹생리염수,Ang-(1-7)조(n=14)수주Ang-(1-7)(25μg·kg-1·h-1),가수술조(n=15)급모형대조조(n=12)칙수주등량적생리염수,4주후검측혈류동역학삼수、혈장화심기AngⅡ농도、좌심실중량지수、심기세포횡경화심기효원용적분수.결과(1)모형대조조동맥수축압、서장압、심솔、좌실수축압(LVSP)、좌심실서장말압、좌실내압최대상승속솔(+dp/dtmax)균명현고우가수술조(P균＜0.01),좌실내압최대하강속솔(-dp/dtmax)저우가수술조(P＜0.01).여모형대조조비교,Ang-(1-7)치료조LVDEP현저감저(P＜0.05),-dp/dtmax승고(P＜0.05),이수축압、서장압、심솔、LVSP급+dp/dtmax재량조간무명현차이.(2)재복주동맥축착술후4주,모형대조조좌심실질량、좌심실질량지수급심기세포횡경명현고우가수술조(P＜0.01),Ang-(1-7)치료조상술지표수고우가수술조,단균명현저우모형대조조(P＜0.05).(3)Ang-(1-7)치료조심기중소혈관주위급심기간질중효원침적수다우가수술조,단명현소우모형대조조(P＜0.05).(4)여가수술조비교,모형대조조화Ang-(1-7)치료조심기중AngⅡ농도균명현증고(P＜0.01),단모형대조조화Ang-(1-7)치료조지간무현저차이(P＞0.05);3조간혈장AngⅡ수평무명현차이(P＞0.05).결론장기정맥수주Ang(1-7)대복주동맥축착인기적동맥압화심기혈관긴장소Ⅱ수평적승고무영향,단사심기비후화섬유화정도현저감경,병보호수손적심공능.
Background To test the hypothesis that chronic administration of angiotensin-(1-7) [Ang-(1-7)] attenuates cardiac hypertrophy in rats in vivo. Methods Coarctation of the suprarenal abdominal aorta was performed in 41 8-week-old male Sprague Dawley rats. Twenty-four hours after the operation, osmotic minipumps were surgically implanted subcutaneously in the rats, which were randomly divided into 3 groups, including a sham-operation group (n=15) receiving infusion with normal saline, a suprarenal aortic coarctation group (n=12), and a suprarenal aortic coarctation group (n=14) with Ang-(1-7) treatment at the dose of 25 μg.kg-1 .h-1. Four weeks later, the systolic and diastolic blood pressures were measured and the left ventricular mass index (LVMI, mg/g) was calculated from the ratio of left ventricular weight to body weight. The concentrations of Ang Ⅱ in the plasma and myocardium were measured by radioimmunoassay, and myocardial interstitial collagen volume fraction (ICVF) was determined by quantitative morphometry of the sections with Picrosirius red staining using an automated image analyzer. Results Suprarenal abdominal aortic coarctation induced a significant increase in carotid artery systolic and diastolic blood pressure, heart weight, LVMI, ICVF, and the concentration of Ang Ⅱ in the myocardium (P＜0.01). Chronic administration of Ang-(1-7) attenuated the increase in the heart weight, LVMI, ICVF and left ventricular diastolic end pressure (LVEDP) caused by suprarenal abdominal aortic coarctation (P＜0.05). Ang-(1-7) also increased the formerly decreased maximum left ventricular pressure reduction rate (-dP/dtmax) (P＜0.05), but had no effect on blood pressure and the concentration of Ang Ⅱ in the myocardium. No difference was noted in plasma concentration of Ang Ⅱ between the 3 groups. Conclusions Ang-(1-7) attenuates cardiac hypertrophy and fibrosis and preserved the impaired left ventricular function induced by left ventricular pressure-overload in rats. These effects are not associated with the changes in the concentrations of AngⅡin the left ventricular myocardium and plasma.