不同剂量辛伐他汀对慢性心力衰竭幼兔蛋白激酶A的影响  

Effects of varying doses of simvastatin on protein kinase A in immature rabbits with chronic heart failure

作　　者：刘迎春[1] 杨秀丽[2] 海体委[2] 孙海燕[2] 武惠敏[2] 王显良[2] 杨萌[2] 赵国安[2] 

机构地区：[1]新乡医学院护理学院,453003 [2]新乡医学院第三附属医院心内科

出　　处：《中华实用儿科临床杂志》2014年第16期1254-1257,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：河南省科技厅课题（092102310203）

摘　　要：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、CI-IF模型组、低剂量辛伐他汀（SD-SIM）组[辛伐他汀剂量为0．3mg／（kg·d）]、中剂量辛伐他汀（MD-SIM）组[辛伐他汀剂量为1．5mg／（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-S1M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。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 simvastafin （ SD-SIM ） group [ SIM concentration was 0.3 mg/（ kg · d） ] , medium-dose simvastatin （ MD-SIM ） group [ SIM concentration was 1.5 rag/（ kg · d） ] , and the high- dose simvastatin （HD-SIM）group [ SIM concentration was 3.0 rag/（ kg · d） 1. The general condition of immature rab- bits in the experiment group was evaluated. Color doppler ultrasonography was used to detect the left ventricular struc- ture and the function. The left ventricular myocardium was taken and fixed in paraformaldehyde （40 g/L）. The expres- sion 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. O- verall 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

关 键 词：辛伐他汀 阿霉素 慢性心力衰竭 蛋白激酶A 

分 类 号：R541.6[医药卫生—心血管疾病]