CAJ | 학술논문

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、3.0 mg/(kg·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(-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,其机制可能与抑制OPG及CTGF表达有关,OPG及CTGF均可成为CHF的预测因子.
목적 관찰불동제량신벌타정(SIM)간예유토만성심력쇠갈(CHF)모형적료효,탐토SIM대유토CHF발휘보호작용적궤제.방법 웅성대이유토60지,안수궤수자표분위5조,정상대조(CON)조,CHF조,저제량신벌타정(SD-SIM)조,중제량신벌타정(MD-SIM)조,고제량신벌타정(HD-SIM)조,매조12지.이연정맥주사염산아매소(ADR),제작CHF모형.우초차주사ADR시즉여신벌타정(SIM)편[제량분별위0.3、1.5、3.0 mg/(kg·d)]제비SD-SIM、MD-SIM화HD-SIM모형.평고실험중유토적일반정황,측량혈류동역학지표,용매련면역흡부법(ELISA)검측골보호소(OPG)표체;면역조직화학법검측심기결체조직생장인자(CTGF)표체;HE염색관찰심기세포결구적변화.결과 1.CON조정황량호,균존활;CHF조、SD-SIM조、MD-SIM조화HD-SIM조대부분출현피부간렬、과도각화、탈모、음식감소、체질량하강、행동완만등증상.총존활솔위76.7％.2.혈류동역학검측현시:여CON조비교,CHF조、SD-SIM조화HD-SIM조좌심실내압최대상승속솔(+ dp/dtmax)、좌심실내압최대하강속솔(-dp/dtmax)급좌심실수축압(LVSP)균명현하강(P균＜0.05).여CHF조비교,SD-SIM조、MD-SIM조화HD-SIM조+dp/dtmax、-dp/dtmax급LVSP균명현승고(P균＜0.01).SD-SIM조、HD-SIM조여MD-SIM조상비명현하강(P＜0.05).3.여CON조비교,CHF조、SD-SIM조、MD-SIM조화HD-SIM조CTGF급OPG표체수평증가,차이유통계학의의(P＜0.01).여CHF조비교,SD-SIM조、MD-SIM조화HD-SIM조CTGF급OPG표체수평감소,차이유통계학의의(P＜0.05).여MD-SIM조비교,SD-SIM조화HD-SIM조CTGF급OPG표체수평증가,차이유통계학의의(P＜0.05).결론 SIM가개선CHF유토좌심실중소、심장공능,MD-SIM조효과최저,기궤제가능여억제OPG급CTGF표체유관,OPG급CTGF균가성위CHF적예측인자.
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 imnunosorbent assay (ELISA).The expression of connective tissue growth factor(CTGF) was evaluated by immunohistochemical assay.Results 1.In CON group,the rabbits were all alive;in CHF,SD-SIM,MD-SIM and HD-SIM groups,most immature rabbits 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),while the expression in the SD-SIM,MD-SIM and HD-SIM groups decreased significantly compared with that of the CHF group (P ＜ 0.05).Compared with the MD-SIM group,the expression of CTGF and OPG in the SD-SIM and HD-SIM groups increased significantly (P ＜ 0.05).Conclusions Simvastatin can improve cardiac function of rabbits with CHF significantly,and the effect on MD-SIM group is the best.The mechanism of simvastatin may depress the expressions of CTGF and OPG.CTGF and OPG can predict CHF.