曲美他嗪对慢性肾衰竭大鼠心肌能量代谢及超微结构的影响  

Effects of trimetazidine on myocardial energy metabolism and ultrastructure in chronic renal failure rats

作　　者：唐琦[1] 梅长林[1] 张黎明[2] 芦怡舟[2] 邬碧波[2] 刘建国[3] 苏定冯[2] 胡惠民[1] 

机构地区：[1]第二军医大学附属长征医院肾内科解放军肾脏病研究所,上海200003 [2]上海市闸北区中心医院肾内科 [3]第二军医大学药学院

出　　处：《中华肾脏病杂志》2011年第8期585-590,共6页Chinese Journal of Nephrology

基　　金：上海市卫生局科技发展基金项目（2009255,2007Y71）;上海市闸北区卫生局科研基金（2009ZBMXK02）

摘　　要：目的观察曲美他嗪（TZM）对慢性肾衰竭大鼠心肌能量代谢及病理结构的影响。方法40只雄性SD大鼠行5／6肾切除术，将成模大鼠随机分为手术对照组、曲美他嗪小剂量（3mg／kg）组、中剂量（6mg／kg）组和大剂量（9mg／kg）组，并设假手术组（雄性SD大鼠10只）。各治疗组大鼠每日灌胃给药，假手术组和手术对照组则予生理盐水，持续17周。实验结束时，测量各组大鼠左心室／体质量、全心／体质量比值；监测平均动脉压及心率；观察心脏超声检查和病理形态学改变，并测定尿素氮（BUN）、血肌酐（Scr）、三磷酸腺苷（ATP）、二磷酸腺苷（ADP）、超氧化物歧化酶（SOD）、丙二醛（MDA）、白细胞介素6（IL-6）、肿瘤坏死因子（TNF）α。结果（1）曲美他嗪中剂量组、大剂量组左室收缩末内径、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显著低于手术对照组（均P〈0．05）。（2）曲美他嗪中剂量组、大剂量组左心室／体质量、全心／体质量均显著低于手术对照组（P〈0．05）。（3）光镜可见手术对照组心肌细胞排列紊乱、肥大，部分心肌纤维化；电镜可见手术对照组心肌组织大片心肌纤维溶解，线粒体增多、肿胀、空泡化，膜断裂。各治疗组心肌病理形态学改变均比手术对照组轻，且随曲美他嗪剂量增大有好转趋势。（4）各组大鼠心率差异无统计学意义，5／6肾切除各组收缩压、舒张压及平均动脉压均显著高于假手术组（P〈0．01），而5／6肾切除各组间收缩压、舒张压及平均动脉压差异均无统计学意义（P〉0．05）。（5）曲美他嗪3个剂量组ATP、ADP均显著高于手术对照组（均P〈0．05），且大剂量组、中剂量组ATP、ADP均显著高于小剂量组（均P〈0．05）。（6）曲美他嗪大剂量组、中剂量组剂量IL-6、TNF-α、MDA均显�Objective To determine the effects of trimetazidine （TMZ） on pathology and energy metabolism of myocardium in chronic renal failure （CRF） rats. Methods CRF models were built in Sprague-Dawley （SD） rats with 5/6 subtotal nephrectomy, and animals were randomyly divided into sham group, control group and three groups treated with different doses of TMZ （3 mg/kg,6 mg/kg or 9 mg/kg）. TMZ was intragastrically administrated to CRF rats for 17 weeks, while physiological saline was used as control. Transthoracic echocardiography was performed and myocardial morphosis was observed. Left ventricular weight/body weight （LVW/BW） and heart weight/body weight （HW/BW） were measured, and heart rate, and mean arterial pressure （MAP） were detected at the end of the study, while several parameters were detected, including urea nitrogen （BUN）, creatinine （Scr）, triphosaden （ATP）, adenosine diphosphate （ADP）, superoxide dismutase （SOD）, malondialdehyde （MDA）, interleukin 6 （IL-6） and tumor necrosis factor α （TNF-α）. Results （1）Left ventricle end-systolic dimensions, anterior wall end-diastolic and end-systolic thicknesses, and posterior wall end-diastolic thickness were significantly lower in rats treated with either medium dose or high dose of TMZ, as compared with control group （P〈0.05）. （2）LVW/BW and HW/BW in rats treated with either medium dose or high dose of TMZ were significantly lower than those in control group （P〈0.05）. （3）Various pathological changes were observed in control group, such as irregular arrangement and hypertrophy of the cardiomyocytes, myocardial fibrosis, mitochondrial swelling, focal muscle fiber dissolution, etc. However, all these pathological changes were apparently ameliorated in TMZ-treated groups, while the beneficial effects of TMZ therapy were dose-dependent. （4）No difference was observed in heart rate among all the groups. Although no difference existed in all the CRF rats, concerning on the systolic/diastolic

关 键 词：肾功能衰竭 慢性 曲美他嗪 心脏 能量代谢 

分 类 号：R285.5[医药卫生—中药学]