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OBJECTIVE@#To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism.@*METHODS@#Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium.@*RESULTS@#Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment.@*CONCLUSIONS@#Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
Subject(s)
Animals , Rats , Blood Urea Nitrogen , Cardiomegaly , Cardiomyopathies , Creatinine , Blood , Drugs, Chinese Herbal , Pharmacology , Heart Ventricles , Indican , Blood , Pharmacology , Myocytes, Cardiac , Metabolism , Nephrectomy , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective Few clinical studies have been reported on the reversibility of uremic cardiomyopathy (UC) after renal transplantation. This article aimed to investigate the cardiac structure and function of end-stage renal disease (ESRD) patients undergoing renal transplantation using cardiac magnetic resonance (CMR). Methods This study included 38 ESRD patients undergoing renal transplantation in the National Clinical Research Center for Kidney Diseases, General Hospital of Eastern Theater Command, from September 2015 to February 2017. All the patients received initial CMR examination at 1－2 days before renal transplantation and during the postoperative follow-up. At the median follow-up time of 3.5 (3.4-3.7), 7.0 (3.7-9.5) and 8.4 (7.1-12.7) months, we recorded the CMR parameters, including the left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic mass (LVEDM), end-systolic mass (LVESM), ejection fraction (LVEF), and native myocardial T1 relaxation time, and compared the parameters obtained before and after surgery. Results Twenty-five of the patients completed the postoperative follow-up, who averaged 27.5 years of age, with no history of diabetes mellitus or ischemic heart disease, and treated by dialysis for 1.7 (1.5-2.2) years. At 7.0 months after renal transplantation, as compared with the baseline, the patients showed significant decreases in the LVEDV ([96.7 ± 22.8] vs [83.4 ± 17.4] mL/m², P < 0.05), LVESV ([44.3 ± 14.8] vs [33.0 ± 10.9] mL/m², P < 0.05) and LVEDM ([67.1 ± 24.2] vs [59.0 ± 17.0] mL/m², P < 0.05), but an increase in the LVEF ([54.1 ± 10.6] % vs [60.9 ± 9.6] %, P < 0.01). The LVEDV and LVESV were also remarkably lower at 3.5 and 8.4 months than the baseline (P < 0.001), and so were the left ventricular at basal, mid, apical and global native T1 relaxation times at 3.5, 7.0 and 8.4 months (P < 0.05). Conclusion For young ESRD patients with no history of diabetes mellitus or ischemic heart disease and on short-term dialysis, left ventricular dilatation, systolic dysfunction and diffuse myocardial fibrosis are reversible after renal transplantation. Native T1 relaxation time can be used as a sensitive indicator to evaluate the degree of diffuse myocardial fibrosis in ESRD patients.
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Objective:To evaluate the effect of left ventricular hypertrophy and deformation on cardiac function in patients with uremic cardiomyopathy (UCM) by using the technology of two dimensional speckle tracking imaging (2D-STI).Methods:A total of 67 UCM patients were randomly divided into the normal cardiac function group (subgroup A,32 cases) and the abnormal cardiac function group (subgroup B,35 cases)according to the New York Heart Association points (NYHA-P).A total of 30 healthy subjetcs served as the control group.Parameters including left ventricular ejection fraction (LVEF),left ventricular mass index (LVMI),left ventricular spherical index (LVSI),left ventricular myocardial mean radial strain (MRS),mean radial strain rate (MRSR),mean longitudinal strain (MLS),local systolic twist angle (STA),and mitral annulus maximum displacement (TMAD) were detected.Results:MLS,MRS,MRSR,LVSI,STA and TMAD in the Group A and Group B were lower than that in the control group (P＜0.05),and LVMI in the Group A and Group B was increased than those in the control group (P＜0.05);LVEE MLS,MRS,MRSR,LVSI and STAin the Group B was decreased than that in the Group A (P＜0.05).MLS in the Group A and B were positively correlated with LVEF and LVSI,but negatively correlated with LVMI.Using the point of 14.10％ for MLS to evaluate UCM patients with NYHA-P＞4 points,the sensitivity,the specificity and Yuedden index were 90.5％,71％ and 0.585,respectively.STA in UCM patients were lower than that in the control (P＜0.05).Conclusion:2D-STI possesses a unique advantage in detecting left ventricular strain and strain rate on left ventricular regional function in UCM with left ventricular hypertrophy and ventricular deformation.There is no direct correlation between the left ventricular hypertrophy and ventricular deformation,but the ventricular hypertrophy and deformation are correlated with regional cardiac function and clinical cardiac function.Left ventricular regional dysfunction may occur before cardiac hypertrophy and deformation.
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Objective To evaluate the effect of imatinib in improving myocardial fibrosis in uremic rats through regulating the expression of PDGFRα.Methods Seventy two rats were divided into three groups ,which were Sham group ,5/6 group and 5/6+I group .All The rats in 5/6 group underwent the 5/6 nephrectomy and the rats in 5/6+I group were given imatinib by ga‐vage after the operation of 5/6 nephrectomy .Hearts were harvested for HE and Sirius red staining at 8 weeks post surgery .The ex‐pression of PDGFRαwas assessed with immunohistological staining .The real‐time PCR was employed to detect the PDGFRαmR‐NA level in hear samples .Results The urine protein ,Scr ,BUN of the 5/6 group and 5/6+I group were higher than that of Sham group(P<0 .01) .The myocardial pathological score in Sham group was significantly lower than that of 5/6 group (P<0 .01) ,and the score in 5/6+I group was significantly lower than that of 5/6 group (P<0 .01) .The collagen volume fraction (CVF) in 5/6 group was significantly higher than that in Sham group (P<0 .01) .And the CVF in 5/6+ I group was higher than that in Sham group (P<0 .05) ,but lower than that of 5/6 group (P<0 .05) .The expression ratio of PDGFRαmRNA and staining rate in 5/6 group and 5/6+I group were both much higher than that in Sham group (P<0 .01) ,and the expression in 5/6+I group was signif‐icantly lower than that in 5/6 group (P<0 .05) .Conclusion These data suggest that the tyrosine kinase inhibitor imatinib reduces heart injury and attenuates myocardial fibrosis in uremic rat by mechanisms associated with the inhibition of the expression of PDGFRα.
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Introducción. La primera causa de muerte en pacientes con insuficiencia renal crónica (IRC) estadios IV y V es la enfermedad cardiovascular (ECV). Objetivo. Identificar ECV en pacientes con IRC estadios IV y V. Método. Se realizó un estudio transversal de Abril de 2013 a Abril de 2014, en el Servicio Nefrológico del Hospital Lucía Íñiguez Landín, Holguín, Cuba. Se seleccionaron 84 pacientes por muestreo sistemático: 48 con IRC estadio IV y 36 en hemodiálisis. Se realizó a cada paciente: examen clínico, electrocardiograma y ecocardiograma 2D con Doppler. Se determinaron: edad, función ventricular, tipo y cantidad (Nº) de ECV. Se utilizó test de Chi cuadrado para asociación de variables. Resultados. Predominaron en los pacientes con IRC estadio IV las edades de 41-50 años (33,3%) y más de 60 años (33,3%), con IRC estadio V el grupo etario de 41-50 años (44,4%; p=0,30). El 91% de los pacientes con IRC estadio IV y el 100% de los estadio V (p=0,20) tenían disfunción diastólica (DD). En los pacientes con IRC estadio IV, la miocardiopatía hipertrófica (MCPH) se identificó en el 50%, la cardiopatía isquémica (CI) en el 25% y la miocardiopatía urémica (MCPU), también, en el 25%; con IRC estadio V, la MCPH fue del 88% (p=0,008), la CI del 66% (p=0,007), las valvulopatías del 55% (p=0,000) y la pericarditis del 33% (p=0,20). El 41% de los pacientes con IRC estadio IV tenían dos lesiones cardíacas y el 77,7% de los pacientes con IRC estadio V tenían más de tres lesiones (p=0,01). Conclusiones. Todos los pacientes con IRC estadio V tenían ECV con DD, la mayoría con más de tres afecciones diferentes; las más frecuentes fueron MCPH, CI y valvulopatías. Mientras que MCPH, CI y MCPU fueron las principales ECV en pacientes con IRC estadio IV.
Cardiovascular disease in patients with stage IV and V of chronic kidney disease Introduction. The cardiovascular disease (CVD) is the first cause of death in patients with stage IV and V of chronic kidney disease (CKD). Objective. To identify the CVD in patients with stage IV and V of CKD. Method. Through a systematic selection, 84 patients (48 stage IV CKD and 36 stage V CKD) were include in a cross-sectional study from April 2013 to April 2014 in the Nephrological Centre of Lucía Íñiguez Hospital, Holguín, Cuba. Clinical examination, electrocardiogram, 2D and Doppler echocardiogram were made to them. Age, ventricular function, type of CVD and number of CVD associated were study. Chi-square test was used as statistical analysis. Results. The ages of 41-50 years (33%) and over 60 years (33%) predominated in patients with stage IV CKD and the ages of 41-50 years (44.4%, p=0.30) in stage V CKD. The 91% of patients with stage IV CKD and the 100% with stage V CKD (p=0.20) had diastolic dysfunction (DD). In patients with stage IV CKD, hypertrophic cardiomyopathy (HMCP) was identified in 50%, coronary artery disease (CAD) in 25% and uremic cardiomyopathy (UMCP) also in 25%; in patients with stage V CKD, the HMCP was 88% (p=0.008), CAD 66% (p=0.007), valvular heart disease (VHD) 55% (p=0.000) and pericarditis 33% (p=0.20). The 41% of patients with stage IV CKD had two ECV and 77.7% of patients with stage V CKD had more than three ECV (p=0.01). Conclusion. All patients with stage V CKD had CVD with DD, most with more than three CVD; HCMP, CAD and VHD were the principal CVD; while HCMP, CAD and UCMP were the principal CVD in patients with stage IV CKD.
Doença cardiovascular em pacientes com doença renal crônica estágio IV e V Introdução. A principal causa de morte em pacientes com renal crônica (DRC) estágio IV e V é a doença cardiovascular (DCV). Objetivo. Identificar DCV em pacientes com DRC estágios IV e V. Método. Um estudo transversal foi realizado de Abril de 2013 a Abril de 2014, no Serviço de Nefrologia do Hospital Lucía Íñiguez Landín, Holguín, Cuba. Foram selecionados por amostragem sistemática 84 pacientes: 48 com DRC estágio IV e 36 com DRC em hemodiálise. Foram submetidos a exame clínico, eletrocardiograma e ecocardiografia 2D e Doppler. Foram determinados: idade, função ventricular, tipo e número (nº) de DCV. Foi utilizado o teste do Qui-quadrado para associação das variáveis. Resultados. Predominou em pacientes com DRC estágio IV as idades de 41-50 anos (33,3%) e >60 anos (33,3%), com DRC estágio V a faixa etária 41-50 anos (44,4%; p=0,30). O 91% dos pacientes com DRC estágio IV e 100% com DRC estágio V (p=0,20) apresentaram disfunção diastólica (DD). Em pacientes com DRC estágio IV, a cardiomiopatia hipertrófica (CMPH) foi identificado em 50%, a doença arterial coronariana (DAC) em 25% e cardiomiopatia urêmica (CMPU) também em 25%; com DRC estágio V, o CMPH foi de 88% (p=0,008), DAC de 66% (p=0,007), doença cardíaca valvular de 55% (p=0,000) e pericardite 33% (p=0,20). O 41% dos pacientes com DRC estágio IV teve duas DCV e 77,7% dos pacientes com DRC estágio V teve mais de três DCV (p = 0,01). Conclusões. Todos os pacientes com DRC estágio V teve CVD com DD, a maioria com mais de três DCV; as mais frequentes foram CMPH, DAC e doença cardíaca valvular. Enquanto CMPH, DAC e CMPU foram o principal DCV em pacientes com DRC estágio IV.