吡那地尔对压力负荷性心力衰竭大鼠心肌重塑的影响

目的探讨吡那地尔对压力负荷性心力衰竭大鼠心功能及心肌重塑的影响。方法腹主动脉缩窄法建立大鼠压力负荷性心力衰竭模型,40只雄性Wistar大鼠随机分为假手术组（n=10）、手术组（n=20）和吡那地尔组（n=10）。吡那地尔组大鼠从术后4周开始应用KATP开放剂吡那地尔2mg·kg-1·d-1治疗。术后第12周行血流动力学检测动脉收缩压、舒张压,左室内压上升下降最大速率（±dp/dtmax）和左室舒张末压（LVDEP）。酶联免疫吸附法（ELISA）测定血清B型脑钠肽（BNP）、I型胶原和Ⅲ型前胶原氨基末端肽（PⅢNP）浓度。处死大鼠后称量心脏质量,计算心脏重量指数（心脏质量/体质量）。HE染色计算心肌纤维直径。结果①手术组大鼠心脏重量指数和心肌纤维直径均明显升高,吡那地尔组均显著降低;②手术组收缩压、舒张压、LVEDP明显升高,吡那地尔组明显降低;±dp/dtmax在手术组明显降低（P〈0.01）。手术组血清BNP水平明显升高,吡那地尔组虽然也降低,但仍高于假手术组（P〈0.01）;③手术组I型胶原和PⅢNP的血清浓度明显大于假手术组。吡那地尔组均明显降低（P〈0.01）。结论吡那地尔可改善大鼠腹主动脉缩窄术后的心脏肥厚和心肌纤维化,延缓心力衰竭的进展。

Effect of pinacidil on myocardial remodeling in pressure overload heart failure rats

Objective To investigate the effects of pinacidil on heart function and myocardial remodeling in pressure overload heart failure rats.Methods Pressure overload heart failure model was established by abdominal aortic constriction.40 male Wistar rats were randomized into 3 groups：sham-operated group（F）,aortic-banded group（T） and Pinacidil group（M）.Rats in M group received Pinacidil 2mg·kg-1·d-1 at the 4th week after operation.Hemodynamic parameters such as systolic blood pressure（SBP）,diastolic blood pressure（DBP）,maximal rising and falling velocity of left intraventricular pressure（±dp/dtmax） and left ventricular end-diastolic pressure（LVEDP） were measured at the 12th week after operation.Serum brain natriuretic peptide（BNP） levels,collagen type I and aminotermianl peptide of type Ⅲ procollagen were tested with ELISA kit.After the rats were sacrificed,the mass indexes of hearts（MI） were calculated（heart mass/body weight）.Myocardial fibre diameters were measured with HE staining.Results ①Compared with F group,MI and the diameters of myocardial fibre in T group were increased dramatically.Pinacidil markedly decreased the above two indexes.②SBP,DBP and LVEDP were higher in T group than F group,and was lower in M group.±dp/dtmax were lower in T group（P0.01）.Serum BNP levels increased significantly in T group.Even though Pinacidil dramatically decreased the BNP level,it still higher than F group（P0.01）.③The serum levels of collagen type I and PⅢNP were both increased significantly in T group as compared with F group（P0.05）.Pinacidil dramatically decrease the above two parameters（P0.01）.Conclusion Pinacidil can improve the myocardial hypertrophy and fibrosis after abdominal aortic constriction,and delay the progression of heart failure.