CAJ | 학술논문

目的探讨大鼠肥厚心肌结构重构、交感神经重构机制及他汀药物的保护作用.方法 62只雄性Wistar大鼠行腹主动脉缩窄术,8周造成压力超负荷性心肌肥厚模型,分为肥厚组和瑞舒伐他汀组,另设22只作为假手术组.瑞舒伐他汀组灌胃给药(10 mg·kg-1·d-1)连续12周后进行超声心动图和血流动力学指标测定.免疫组化法测定心肌中酪氨酸羟化酶(TH)和生长相关因子43(GAP43),Western印迹法检测心肌的TH、GAP43和神经生长因子(NGF)表达水平.结果 (1)肥厚组左室重量(LVW)、左室重量指数(LVWI)、室间隔厚度(IVSd)、左心室后壁厚度(PWd)、左心室舒张末期内径(LVEDd)、左心室收缩末压(LVSP)、收缩期左心室内压最大变化速率(+dp/dtmax)和舒张期左心室内压最大变化速率(-dp/dtmax)均高于假手术组和瑞舒伐他汀组.(2)Western印迹显示,肥厚组比假手术组,NGF、GAP43分别增加了1.5倍和1.7倍.瑞舒伐他汀组均低于肥厚组,分别降低46.4%(0.82±0.06比1.53±0.10)和16%(0.68±0.06比0.81±0.10).肥厚组比假手术组,TH水平降低45.7%(0.44±0.10比0.81±0.10),瑞舒伐他汀组(0.62±0.06)比肥厚组增高41%.结论压力超负荷性大鼠肥厚心肌出现结构重构、交感神经重构现象;他汀药物能改善肥厚心肌的结构重构和交感神经重构.
목적 탐토대서비후심기결구중구、교감신경중구궤제급타정약물적보호작용.방법 62지웅성Wistar대서행복주동맥축착술,8주조성압력초부하성심기비후모형,분위비후조화서서벌타정조,령설22지작위가수술조.서서벌타정조관위급약(10 mg·kg-1·d-1)련속12주후진행초성심동도화혈류동역학지표측정.면역조화법측정심기중락안산간화매(TH)화생장상관인자43(GAP43),Western인적법검측심기적TH、GAP43화신경생장인자(NGF)표체수평.결과 (1)비후조좌실중량(LVW)、좌실중량지수(LVWI)、실간격후도(IVSd)、좌심실후벽후도(PWd)、좌심실서장말기내경(LVEDd)、좌심실수축말압(LVSP)、수축기좌심실내압최대변화속솔(+dp/dtmax)화서장기좌심실내압최대변화속솔(-dp/dtmax)균고우가수술조화서서벌타정조.(2)Western인적현시,비후조비가수술조,NGF、GAP43분별증가료1.5배화1.7배.서서벌타정조균저우비후조,분별강저46.4%(0.82±0.06비1.53±0.10)화16%(0.68±0.06비0.81±0.10).비후조비가수술조,TH수평강저45.7%(0.44±0.10비0.81±0.10),서서벌타정조(0.62±0.06)비비후조증고41%.결론 압력초부하성대서비후심기출현결구중구、교감신경중구현상;타정약물능개선비후심기적결구중구화교감신경중구.
Objective To explore the remodeling mechanism of myocardium and sympathetic nerve in pressure overload left ventricular hypertrophy and elucidate the protective effect of statins. Methods Pressure-overload left ventricular hypertrophy (LVH) of rats was induced by partial coarctation of abdominal aorta; a sham-operated group served as the control (SHAM, n=22). At 8 weeks pest-operation, the animals were divided into two groups and a 12-week treatment period was investigated. At the end of treatment period, eehocardiographic evaluations and hemodynamic measurements were performed. Sympathetic innervation was investigated by analyzing nerve growth factor (NGF), growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). Results In LVH rats, a significant increase of left ventricular weight, left ventricular weight/body weight, echocardiographic left ventricular end-diastolic diameter, interventricular septum thickness, posterior left ventricular wall thickness, left ventricular systolic pressure and dP/dt was observed. The expressions of NGF and GAP43 protein were significantly down-regulated (0.82±0.06 vs 1.53±0.10, 0.68±0.06 vs 0.81±0.10) and TH level was up-regulated (0.44±0.10 vs 0.62±0.06) by RSV treatment. Conclusion A HMG CoA inhibitor reverses the development of left ventrieular hypertrophy and inhibits sympathetic innervation in abdominal aortic-clamped animals.