Effects of trimetazidine on myocardial energy metabolism and ultrastructure in chronic renal failure rats
10.3760/cma.j.issn.1001-7097.2011.08.008
- VernacularTitle: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
- Author:
Qi TANG
;
Changlin MEI
;
Liming ZHANG
;
Yizhou LU
;
Bibo WU
;
Jianguo LIU
;
Dingfeng SU
;
Huimin HU
- Publication Type:Journal Article
- Keywords:
Kidney failure,chronic;
Trimetazidine;
Heart;
Energy metabolism
- From:
Chinese Journal of Nephrology
2011;27(8):585-590
- CountryChina
- Language:Chinese
-
Abstract:
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 physiologicalsalinewasusedascontrol. Transthoracicechocardiographywasperformedand 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 (l)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 blood pressure and mean arterial pressure (P＞0.05), these parameters were elevated in CRF rats, as compared with sham-operated group(P＜0.01). (5)ATP and ADP in TMZ-treated rats were significantly higher as compared with control(P＜0.05), moreover, medium dose and high dose of TMZ were superior to low dose (P＜0.05).(6)SOD was significantly increased in TMZ-treated rats (P＜0.05), while IL-6,TNF-α and MDA were significantly decreased in medium dose and high dose of TMZ, as compared with control(P＜0.05).Conclusion TMZ may prevent myocardial fibrosis and left ventricular hypertrophy in chronic renal failure via ameliorating myocardial energy metabolism and alleviating inflammatory reaction and oxidative stress.
