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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 investigate the effect of trimetazidine on left ventricular remodeling in rats with chronic renal failure and the changes of plasma brain natriuretic peptide (BNP). Methods SD rats were randomly divided into sham operation group, operation control group and trimetazidine small, medium and large dose (3, 6, 9 mg / kg) treatment group, 10 rats in each group; / 6 nephrectomy model of chronic renal failure, the latter three groups of rats administered daily gavage, the control group was given an equal volume of saline for 17 weeks. At the end of the experiment, the heart of rat was examined by ultrasound, the systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were measured. The plasma BNP was measured. The pathological changes of heart were observed. Results The results of echocardiography showed that the mean diameter of left ventricular end-systole, the anterior wall thickness of left ventricular end-diastolic space, the anterior wall thickness of left ventricular end-systolic cavity, and the thickness of left ventricular end-diastolic wall in trimetazidine group were significantly lower than those in trimetazidine group Surgical control group (P <0.05). The systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and plasma BNP levels were lower in the sham operation group than those in the other 4 groups (P <0.01, P <0.05). The BNP levels in the trimetazidine and high-dose treatment groups were lower than those in the control group P <0.05). Under the light microscope, the myocardial cells in the control group were disordered, hypertrophy and some myocardial fibrosis. The myocardial fibrosis was found in the control group, which was caused by the dissolution of mitochondria, swelling and vacuolization. Compared with the surgery The control group improved, and with trimetazidine dose to further improve the trend. Conclusion Trimetazidine can decrease plasma BNP level and improve left ventricular remodeling in rats with chronic renal failure.