罗格列酮联合阿米洛利治疗对老年SD大鼠心脏结构及功能的影响

目的：通过保钾利尿剂阿米洛利治疗长期应用罗格列酮的老年SD大鼠，在观察其疗效和安全性的同时评价阿米洛利对罗格列酮导致心肌损伤的保护作用，并探讨可能的机制。方法将40只SD大鼠分为对照组、罗格列酮组、阿米洛利组、阿米洛利联合罗格列酮组，每组10只。3周龄起灌胃给药，时间6个月。每月采血行生化检测，观察血电解质、尿电解质、肾功能、血糖、血脂等指标。6个月后行心脏超声检查观察大鼠心脏功能。大鼠处死后称取心、肝、肾，留取组织行病理检查，观察各脏器的病理学状态。观察罗格列酮和阿米洛利对相关指标的影响。结果药物干预SD大鼠6个月后，罗格列酮组出现明显血钠偏高，联合用药组血钠水平介于罗格列酮组与对照组之间。心脏超声检查发现罗格列酮组大鼠的左室后壁收缩期厚度与舒张期厚度、收缩期室间隔厚度与舒张期室间隔厚度均有所增加，而联合用药组心脏超声各项指标与对照组差异无统计学意义。心肌组织学检查中罗格列酮组出现心肌组织受损，而联合用药组基本无心肌组织破坏。结论罗格列酮可加重心肌损伤，联用阿米洛利可减轻罗格列酮治疗中对心脏的副作用。

Effect of rosiglitazone combined with amiloride on heart structure and function in senile SD rats

Objective To investigate the protective effect and safety of amiloride, a potassium-sparing diuretic, on the injured heart in senile SD rats with long term rosiglitazone treatment and study the possible underlying mechanism. Methods Forty senile rats were divided into 4 groups： control group, rosiglitazone treatment group [10mg/（kg＆#183;d）], amiloride treatment group [5mg/（kg＆#183;d）], and combined treatment group （dose as the single treatment group）, with 10 rats in each group. The rats received intra-gastrical administration for 6 months after delactation at 2 weeks old. Blood and urinary electrolytes, renal function, blood glucose and blood lipids were measured every month. The heart function was evaluated by heart ultrasonography in the end of 6 months treatment. Pathological changes in the heart, liver and kidneys were observed with hematoxylin-eosin （HE）, periodic acid-Schiff （PAS） and Masson staining after the rats were sacrificed. The effect of rosiglitazone and amiloride on above indices were studied. Results In 6 months after the treatment, the serum sodium was obviously increased in rosiglitazone treatment group, but that in the combined treatment group stood between the rosiglitazone treatment group and normal control. Ultrasound examination showed that left ventricular posterior wall thickness systolic （LVPWTs） and diastolic （LVPWTd）, and interventricular septal thickness systolic （IVSTs） and diastolic （IVSTd） were increased in the rosiglitazone treatment group, but there was no difference in these indices between the combined treatment group and the control group. Myocardial damages were found in rosiglitazone treatment group, but none in the combined treatment group. Conclusion Rosiglitazone aggravate the myocardial damages, while amiloride should be used to relieve the side effect of rosiglitazone.