CAJ | 학술논문

目的通过观察不同剂量辛伐他汀对慢性心力衰竭(CHF)幼兔蛋白激酶A(PKA)、心室重塑及心功能的影响,探讨辛伐他汀治疗CHF的可能机制.方法 60只雄性幼兔按随机数字表分为5组:正常对照(CON)组、CHF模型组、低剂量辛伐他汀(SD-SIM)组[辛伐他汀剂量为0.3 mg/(kg·d)]、中剂量辛伐他汀(MD-SIM)组[辛伐他汀剂量为1.5 mg/(kg· d)]以及高剂量辛伐他汀(HD-SIM)组[辛伐他汀剂量为3.0mg/(kg·d)].评估幼兔一般情况,对其行心脏彩超检查,测量其左心室结构和功能.留取其左心室心肌于40g/L多聚甲醛中固定,免疫组织化学法检测PKA表达.结果 CON组全部存活,其他组大部分出现脱毛、饮食减少、体质量下降、行动缓慢等表现.总存活率为82％(49/60只).CHF组病死率显著高于MD-SIM组(41.7％比8.3％,P＜0.05) 心功能检查显示:与CON组相比,SD-SIM组、HD-SIM组、CHF模型组左心室射血分数(LVEF)明显下降(P均＜0.01),左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)均明显升高(P均＜0.01);与CHF模型组相比,MD-SIM组、SD-SIM组及HD-SIM组LVEDd、LVESd均明显下降,LVEF明显升高(P均＜0.05),其中 MD-SIM组效果最显著(P均＜0.05).PKA在心肌的表达:与CON组和CHF模型组相比,SD-SIM组、MD-SIM组、HD-SIM组PKA表达明显增多(P均＜0.01),其中MD-SIM组与 SD-SIM组、HD-SIM相比表达更多(P均＜0.05).结论辛伐他汀可明显逆转CHF幼兔左心室重塑,改善心功能,MD-SIM组效果最佳,机制可能与其上调PKA表达有关.
목적 통과관찰불동제량신벌타정대만성심력쇠갈(CHF)유토단백격매A(PKA)、심실중소급심공능적영향,탐토신벌타정치료CHF적가능궤제.방법 60지웅성유토안수궤수자표분위5조:정상대조(CON)조、CHF모형조、저제량신벌타정(SD-SIM)조[신벌타정제량위0.3 mg/(kg·d)]、중제량신벌타정(MD-SIM)조[신벌타정제량위1.5 mg/(kg· d)]이급고제량신벌타정(HD-SIM)조[신벌타정제량위3.0mg/(kg·d)].평고유토일반정황,대기행심장채초검사,측량기좌심실결구화공능.류취기좌심실심기우40g/L다취갑철중고정,면역조직화학법검측PKA표체.결과 CON조전부존활,기타조대부분출현탈모、음식감소、체질량하강、행동완만등표현.총존활솔위82％(49/60지).CHF조병사솔현저고우MD-SIM조(41.7％비8.3％,P＜0.05) 심공능검사현시:여CON조상비,SD-SIM조、HD-SIM조、CHF모형조좌심실사혈분수(LVEF)명현하강(P균＜0.01),좌심실서장말기내경(LVEDd)、좌심실수축말기내경(LVESd)균명현승고(P균＜0.01);여CHF모형조상비,MD-SIM조、SD-SIM조급HD-SIM조LVEDd、LVESd균명현하강,LVEF명현승고(P균＜0.05),기중 MD-SIM조효과최현저(P균＜0.05).PKA재심기적표체:여CON조화CHF모형조상비,SD-SIM조、MD-SIM조、HD-SIM조PKA표체명현증다(P균＜0.01),기중MD-SIM조여 SD-SIM조、HD-SIM상비표체경다(P균＜0.05).결론 신벌타정가명현역전CHF유토좌심실중소,개선심공능,MD-SIM조효과최가,궤제가능여기상조PKA표체유관.
Objective To investigate the effects of varying doses of simvastatin (SIM) on protein kinase A (PKA),ventricular remodeling and heart function in immature rabbits with chronic heart failure (CHF),to explore the possible mechanisms for simvastatin on CHF.Methods Sixty male immature rabbits were randomly divided into 5 groups:control (CON) group,CHF model group,small-dose simvastatin (SD-SIM) group [SIM concentration was 0.3 mg/(kg · d)],medium-dose simvastatin (MD-SIM)group[SIM concentration was 1.5 mg/(kg · d)],and the highdose simvastatin (HD-SIM)group[SIM concentration was 3.0 mg/(kg · d)].The general condition of immature rabbits in the experiment group was evaluated.Color doppler ultrasonography was used to detect the left ventricular structure and the function.The left ventricular myocardium was taken and fixed in paraformaldehyde (40 g/L).The expression of PKA was evaluated by immunohistochemical assay.Results In CON group,the rabbits were all alive; in the other groups,most immature rabbits were unhairing,with diet reduction,weight lose and sluggish with hyperkeratosis.Overall survival rate was 82％ (49/60 cases).The mortality rate in CHF model group was significantly higher than that in the MD-SIM group(41.7％ vs 8.3％,P ＜ 0.05).Compared with the CON group,left ventricular ejection fraction (LVEF) in the SD-SIM group,HD-SIM group and CHF model group all dropped sharply (all P ＜ 0.01),while the left ventricular end diastolic diameter (LVEDd) and left ventricular end systolic diameter (LVESd) increased markedly (all P ＜0.01).Compared with CHF model group,LVEDd and LVESd decreased and LVEF increased significantly in SD-SIM group,HD-SIM group and MD-SIM group (all P ＜ 0.05),the effects of MD-SIM group was the best (P ＜0.05).LVEF in MD-SIM group increased significantly compared with SD-SIM group,HD-SIM group and CHF model group (all P ＜ 0.05).PKA expression in SD-SIM group,MD-SIM group and HD-SIM group increased significantly compared to the CHF model group and CON group (all P ＜ 0.01).Compared with the SD-SIM group and HD-SIM group,the expression of MD-SIM group significantly increased (P ＜ 0.05).Conclusions Simvastatin can reverse the left ventricular remodeling and improve the heart function of immature rabbits with CHF.The effect of MD-SIM was the best.The mechanism of simvastatin may be correlated to up-regulating the expression of PKA.