Heart protection of L-carnitine in chronic renal failure rats / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats (CRF). Methods A total of 55 male SD rats were randomly divided into sham group (n=10),model group (n=15),low dose (300 mg/kg),medium dose (600 mg/kg) and high dose (900 mg/kg) L-carnitine group(n=10,each).5/6 subtotal nephrectomy was performed in these rats without sham group.One week after the operation,normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks.Transthoracic echocardiography,mean arterial pressure (MAP),heart rate (HR) and heart weight/body weight were assessed.Moreover,24h urine protein,renal function,SOD,MDA,IL-6,ATP,ADP were measured at the end of the study.Additionally,pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results (1) ATP (μmol/g·wt)in L-carnitine groups (2.35±0.24,3.59±0.28,3.78±0.25) was significantly higher than that in model group (1.61±0.12) (all P＜0.01).(2) Thickness of posterior wall of left ventricle (mm) in high dose L-carnitine group was thinner than that in model group (3.74±0.23 vs 4.18±0.48,P＜0.05). (3) The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups (3.92±0.27,3.65±0.2) were significantly lower compared to model group (3.99±0.27) (all P＜0.01). (4) Under light microscopy,disarrangement and hypertrophy of cardiac myocytes,increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-carnitine groups (7.14±1.07,6.13±0.99),as compared with model group (9.88±1.13) (all P＜0.01).Under electron microscopy,typical changes in cardiac hypertrophy were observed,including dissolution of myocardial fibers,increasing and swelling of mitochondria,membrane rupture as well as matrix increase in model group,while these changes were ameliorated by L-carnitine in a dose-dependent manner. (5) Seventeen weeks after the treatment,both IL-6 and MDA were decreased in all L-carnitine-treated groups than those in model group [IL-6 (ng/L)261.86±13.18,240.12±18.7,233.34±36.88 vs 596.64±81.41; MDA (nmol/L)15.23±2.01,12.41±0.6.10.97±1.9 vs 21.84±2.71).Whereas,SOD (U/ml) were increased in L-carnitine-treated groups (51.2±6.11,58.51±5.52,60.63±6.94) than that in model group(32.01 ±5.69 )(all P＜0.05).(6) No significant differences of systolic,diastolic blood pressure or MAP were found among groups. Conclusion L-carnitine can improve energy metabolism,micro-inflammation and oxidative stress in myocardium of CRF rats,which may be associated with the amelioration of cardiac hypertrophy and fibrosis.