不同剂量辛伐他汀对慢性心力衰竭幼兔结缔组织生长因子及骨保护素的影响  

Effects of different doses of simvastatin on connective tissue growth factor and osteoprotegerin of immature rabbits with chronic heart failure

作　　者：杨秀丽[1] 刘迎春[1] 邵锋[1] 孙海燕[1] 任可[1] 武惠敏[1] 王显良[1] 赵国安[1] 

机构地区：[1]新乡医学院第三附属医院心内科,河南新乡453003

出　　处：《中华实用儿科临床杂志》2014年第11期866-870,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：河南省科技厅课题（092102310203）

摘　　要：目的观察不同剂量辛伐他汀（SIM）干预幼兔慢性心力衰竭（CHF）模型的疗效，探讨SIM对幼兔CHF发挥保护作用的机制。方法雄性大耳幼兔60只，按随机数字表分为5组，正常对照（CON）组，CHF组，低剂量辛伐他汀（SD-SIM）组，中剂量辛伐他汀（MD．SIM）组，高剂量辛伐他汀（HD—SIM）组，每组12只。耳缘静脉注射盐酸阿霉素（ADR），制作CHF模型。于初次注射ADR时即予辛伐他汀（SIM）片[剂量分别为0．3、1．5、3．0mg／（k·d）]制备SD—SIM、MD—SIM和HD—SIM模型。评估实验中幼兔的一般情况，测量血流动力学指标，用酶联免疫吸附法（ELISA）检测骨保护素（OPG）表达；免疫组织化学法检测心肌结缔组织生长因子（CTGF）表达；HE染色观察心肌细胞结构的变化。结果1．CON组情况良好，均存活；CHF组、SD—SIM组、MD—SIM组和HD—SIM组大部分出现皮肤干裂、过度角化、脱毛、饮食减少、体质量下降、行动缓慢等症状。总存活率为76．7％。2．血流动力学检测显示：与CON组比较，CHF组、SD—SIM组和HD—SIM组左心室内压最大上升速率（＋dp／dtmax）、左心室内压最大下降速率（一dp／dtmax）及左心室收缩压（LVSP）均明显下降（P均〈0．05）。与CHF组比较，SD-SIM组、MD—SIM组和HD—SIM组＋dp／dtmax、-dp／dtmax及LVSP均明显升高（P均〈0．01）。SD—SIM组、HD—SIM组与MD—SIM组相比明显下降（P〈0．05）。3．与CON组比较，CHF组、SD—SIM组、MD—SIM组和HD—SIM组CTGF及OPG表达水平增加，差异有统计学意义（P〈0．01）。与CHF组比较，SD—SIM组、MD—SIM组和HD—SIM组CTGF及OPG表达水平减少，差异有统计学意义（P〈0．05）。与MD．SIM组比较，SD—SIM组和HD—SIM组CTGF及OPG表达水平增加，差异有统计学意义（P〈0．05）。结论SIM可改善CHF幼兔左心室重塑、心脏功能，MD—SIM组效果最著，其机制可�Objective To observe the effects of different doses of simvastatin on immature rabbit models of chronic heart failure（CHF） and to explore the mechanism of simvastatin in the rabbits with CHF. Methods Sixty male immature rabbits were randomly divided into 5 groups ： control （CON） group, CHF group, small-dose simvastatin （ SD- SIM） group,medium-dose simvastatin （MD-SIM） group, and the high-dose simvastatin （HD-SIM） group, 12 cases in each group. The models of CHF were established by injecting adriamycin（ADR） via the auricular vein of rabbits. In the first injection of ADR, simvastatin tablets [ concentration of 0.3,1.5,3.0 mg/（ kg ~ d）, respectively ] were given to the rabbits by intragastric administration for SD-SIM, MD-SIM, and HD-SIM models. The general conditions of immature rabbits in experiment group were evaluated. Hemodynamic data were detected. HE staining was used to observe structure of myocardial cells. The plasma level of osteoprotegerin （OPG） was measured by enzyme-linked immunosorbent assay （ELISA）. The expression of connective tissue growth factor（CTGF） was evaluated by immunohistochemical assay. Re- sults 1. In CON group,the rabbits were all alive;in CHF,SD-SIM,MD-SIM and HD-SIM groups,most immature rab- bits had skinchapped, unhaired and sluggish with hyperkeratosis, diet reduction, and losing weight. Overall survival rate was 76.7%. ：2. Hemodynamic data indicated that the ＋ dp/dtmax,-dp/dtmax and the left ventricular systolic pressure （LVSP） in the SD-SIM, HD-SIM and CHF groups dropped significantly compared with the CON group （ all P 〈 0.05 ）. There was a remarkable increase in the SD-SIM, HD-SIM and MD-SIM groups compared with CHF group （ all P 〈 0. 01 ） ;and there was a remarkable drop in the cardiac function of the SD-SIM and HD-SIM groups compared with MD- SIM group （ P 〈 0.05 ）. 3. Compared with the CON group, CTGF and OPG expression in the SD-SIM, MD-SIM, HD-SIM and CHF groups increased significantly （P 〈 0.01 ） ,wh

关 键 词：辛伐他汀 慢性心力衰竭 结缔组织生长因子 骨保护素 

分 类 号：R541.6[医药卫生—心血管疾病]