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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.
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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.
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Objective To investigate the effects of levocarnitine combined with urimetazidine on left ventricular remodeling in maintenance hemodialysis(MHD)patients.Methods All of 86 MHD patients and 40 healthy volunteers(health control group)were involved in the study.all of 86 MHD patients were randomly divided into two groups,disease treatment group(46 cases)and disease control group(40 cases),who had undergone hemodialysis for at least 3 months before the study and were in a stable clinical status without signs of infection or disease activity.In disease treatment group,1.0 g of levocarnitine was infused at the end of each dialysis treatment and 20 mg of trimetazidine was taken orally 3 times each day for 6 months,while the parameters for free fatty acid(FFA),free carnitine(FC),inflammation and oxidative stress were studied before and after the treatmenL In disease control group these two drugs were not used.The left ventricular end-diastolic diameter(LVDd),left ventricuhr end-systolic diameter(LVDs),left atrial diameter (LAD),left ventricular posterior wall thickness(LVPWT),interventricular septal thickness(IVST)and left ventricular ejection fraction(LVEF)were detected by ultrasonic cardiography.Results Before treatment,the serum levels of FFA,high-sensitivity C-reactive protein(hs-CRP),intedeukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-αand malondialdehyde(MDA)were higher in disease treatment group and disease control group than those in health control group(P<0.05 or<0.01),while the serum levels of FC,glutathione peroxidase(GSHPx)and superoxide dismutase(SOD)were lower in disease treatment group and disease control group than those in health control group(P<0.05 or<0.01).Compared with those before treatment,the serum levels of FFA,hs-CRP,IL-1β,IL-6,TNF-α,MDA were decreased(P<0.05 or<0.01),FC,GSHPx,SOD were increased(P<0.05 or<0101),the scores of LVDd,LAD,IVST,LVPWT,LVMI were also decreased significantly(P<0.05),while LVEF increased markedly after treatmem in disease treatment group(P<0.05).There were significant differences in all indexes between disease treatment group and disease control group(P<0.05 or<0.01).Conclusion Supplements of levocarnitine combined with trimetazidine in MHD patients appear to be associated with an improvement of left ventricular remodeling.
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Objective To investigate the serum level of free fatty acid (FFA) and explore its relationship with cytokines and atherosclerosis (AS) in chronic kidney disease (CKD).Methods The serum level of FFA was determined with enzymatic colorimetry.IL-1 β, IL-6 and TNFα were determined with ELISA.High-sensitivity C-reactive protein (hsCRP) was measured with immunoturbidimetry.Prevalence of atherosclerosis was detected with carotid ultrasonography.We evaluated the relationship between serum levels of FFA and IL-1β,IL-6, TNFα, hsCRP as well as the renal function in 130 adult patients with CKD, stratified according to the GFR ( based on the National Kidney Foundation/Kidney Dialysis Outcomes Quality Initiatives) and in 58 hemodialytic (HD) patients.The relationship between FFA level and cardiac geometry incidence in CKD patients was analyzed with logistic regression model.Results The serum level of FFA was significantly higher in CKD patients as compared with that in the healthy controls [(492.63 ± 143.59)vs (302.65 ± 142.18) μ mol/L, P ＜ 0.01], even in the early stage of CKD.The level of FFA increased with the progression of renal dysfunction.In the non-dialytic CKD group, the level of FFA was negatively related to GFR and positively related to the proteinuria (P ＜ 0.05), while in the HD group, it was positively correlated with dialysis duration ( P ＜ 0.05 ).The serum levels of FFA were higher in CKD patients with carotid artery atherosclerosis than those in patients without ( P ＜ 0.05 or ＜ 0.01 ).However, in both groups with impairment of renal function, the levels of FFA were positively correlated with hsCRP, IL-1 β, IL-6,TNFα and TG( all P ＜ 0.05 ).A positive correlation between the level of FFA and the clinical manifestations such as carotid intimal medial thickness (IMT) and AS was also found.A negative correlation was found between the level of FFA and the serum level of albumin and GFR( P ＜ 0.05).Conclusion Serum levels of FFA are significantly higher either in non-dialytic CKD or in HD patients and it is related with hsCRP, IL-1 β, IL-6, TNFα as well as carotid artery atherosclerosis, indicating that FFA is an independent risk factor of AS in CKD.