曲美他嗪对慢性肾衰竭大鼠左心室重塑及血浆脑钠素的影响

Effects of trimetazidine on left ventricular remodeling and plasma brain natriuretic peptide level in rats with chronic renal failure

目的观察曲美他嗪对慢性肾衰竭大鼠左心室重塑的影响及血浆脑钠素(BNP)的变化。方法 SD大鼠随机分为假手术组、手术对照组及曲美他嗪小、中、大剂量(3、6、9 mg/kg)治疗组,每组10只;后4组大鼠建立5/6肾切除术慢性肾衰竭模型,后3组大鼠每日灌胃给药,手术对照组则给予等量生理盐水,持续17周。实验结束时,对大鼠心脏进行超声检查,监测收缩压、舒张压、平均动脉压及心率,测定血浆BNP,并取心脏组织进行病理形态学观察。结果心超检查结果表明:曲美他嗪中、大剂量组大鼠左室收缩末内径、左室舒张末期前壁厚度、左室收缩末期前壁厚度、左室舒张末期后壁厚度均低于手术对照组(P<0.05)。假手术组收缩压、舒张压及平均动脉压、血浆BNP水平均低于其余4组(P<0.01,P<0.05);曲美他嗪中、大剂量治疗组BNP均低于手术对照组(P<0.05)。光镜下可见手术对照组心肌细胞排列紊乱、肥大,部分心肌纤维化;电镜下手术对照组可见大片心肌纤维溶解,线粒体增多、肿胀、空泡化;曲美他嗪治疗组心肌损伤均较手术对照组改善,且随曲美他嗪剂量增大有进一步好转趋势。结论曲美他嗪降低血浆BNP水平,可改善慢性肾衰竭大鼠左心室重塑。

Objective To observe the effects of trimetazidine（TMZ） on left ventricular remodeling and plasma brain natriuretic peptide（BNP） level in rats with chronic renal failure（CRF）.Methods Male Sprague-dawley（SD） rats were randomly divided into sham group,CRF group,small-（3 mg/kg）,medium-（6 mg/kg）,and high-TMZ（9 mg/kg） treatment groups,with each group containing 10 rats.Animals in the latter four groups received 5/6 subtotal nephrectomies.TMZ was intragastrically administered to rats for 17 weeks in three TMZ groups,while normal saline was given to rats in CRF group.At the end of the study,transthoracic echocardiography was performed,the systolic blood pressure（SBP）,diastolic blood pressure（DBP）,mean arterial pressure（MBP）,and BNP were measured,and the cardiac tissues were obtained for pathological examination.Results Echocardiography showed that the left ventricle end-systolic dimensions,anterior wall end-diastolic and end-systolic thicknesses,and posterior wall end-diastolic thickness in the medium-and high-TMZ groups were significantly decreased compared with those in the sham control group（P〈0.05）.Compared with the sham control group,the rest four groups had significantly higher systolic/diastolic blood pressure,mean arterial pressure and BNP level （P〈0.01,P〈0.05）.The BNP levels in medium-and high-TMZ groups were significantly lower than that in the sham control group（P〈0.05）.Irregular arrangement and hypertrophy of the cardiomyocytes and myocardial fibrosis were observed in the control group under light microscope,and mitochondrial swelling,vacuolation and focal muscle fiber dissolution were observed under electron microscope.The pathological changes were improved by TMZ treatment in a dose-dependent manner.Conclusion TMZ may improve left ventricular remodeling and decrease BNP level in CRF rats.