辛伐他汀减轻舒张功能不全心力衰竭大鼠心肌纤维化

The Protective Effect of Simvastatin on Myocardial Fibrosis of Rats with Diastolic Heart Failure

目的探讨辛伐他汀对舒张功能不全心力衰竭(diastolic heart failure,DHF)大鼠心脏功能保护和心肌纤维化的影响。方法雄性SD大鼠30只,随机分为阴性对照组、DHF组、辛伐他汀组。采用腹主动脉缩窄建立DHF模型,阴性对照组只开腹和分离腹主动脉。辛伐他汀组大鼠术后经灌胃给予辛伐他汀2 mg/(kg.d),阴性对照组和DHF组大鼠给予同等量的生理盐水。4周末心脏超声检测心功能,颈动脉插管记录血流动力学,HE染色和Masson染色观察心肌组织病理结构的变化。结果心脏超声显示DHF组大鼠室间隔和左心室后壁厚度、E/A比值明显增高,血流动力学检测显示收缩压、舒张压、左心室收缩压、左心室舒张末压升高,左心室松弛时间常数延长,左心室内压最大下降速率下降,心脏指数和左心室质量指数增加。辛伐他汀使增加的室间隔和左心室后壁厚度、E/A、收缩压、舒张压、左心室收缩压、左心室舒张末压、心脏指数和左心室质量指数降低,左心室松弛时间常数缩短,左心室内压最大下降速率升高。HE染色和Masson染色显示,DHF组大鼠心肌组织间纤维组织和炎性细胞增多,心肌胶原面积与总面积的比值和壁内小动脉管腔周围胶原面积与管腔面积的比值在心肌组织中显著增加;辛伐他汀减轻DHF大鼠心肌组织间纤维化和炎性细胞浸润,降低心肌胶原面积与总面积的比值以及壁内小动脉管腔周围胶原面积与管腔面积的比值。结论辛伐他汀改善DHF大鼠心脏功能,此作用可能与减轻心室纤维化有关。

Aim To study the effect of simvastatin on cardiac fibrosis of rats with diastolic heart failure （DHF）. Methods 30 SD rats were randomly divided into three groups： control group, DHF group and simvastatin group. DHF model was produced by abdominal aortic coarctation in the rats. The rats in simvastatin group were given simvastatin 2 mg/（kg d） by intragastric administration for 4 weeks, the others were treated with equal isotonic Na chloride. After 4 weeks, cardiac function and hemorheology were assessed by echocardiography and catheterization. HE and Masson stain- ings were applied to observe altered myocardial histopathology and myocardial fibrosis, respectively. Results In DHF group, IVS, LVPWT, LVMI, E/A ratio, SBP, DBP, LVSP, LVEDP, fiber tissue, ventricular perivascular collagen area （CA）, inflammatory cell invasion and collagen volume fraction （CVF） were increased. Tau was prolonged and LV -dp/dtmax was decreased. While in simvastatin group E/A ratio, IVS, LVPWT, LVMI, SBP, DBP, LVSP, LVEDP, inflammatory cell invasion, fiber tissue, CA and CVF were significantly decreased, prolonged Tau was shortened, and LV - dp/dtmax was increased compared with DHF group. Conclusion Simvastatin improves cardiac diastolic function in rats with DHF by ameliorating myocardial fibrosis.