Establishment Of Uremic Cardiomyopathy Model In Rodents

BackgroundCardiovascular complications are the main reason affecting the prognosis of patients with chronic kidney disease(CKD).Uremic cardiomyopathy is a common feature of cardiovascular diseases in CKD patients,and is the pathological basis of more serious cardiovascular diseases(such as heart failure,arrhythmia and sudden death)in these patients.Therefore,uremic cardiomyopathy is considered as the main therapeutic target for CKD with cardiovascular complications.The establishment of stable uremic cardiomyopathy model is the prerequisite of relevant translational studies.Uremic cardiomyopathy model establishment is mainly based on the methods of CKD model construction,such as 5/6 nephrectomy and adenine feeding.However,there are different realization conditions for establishing uremic cardiomyopathy model at present,including strain selection,duration,with or without the aid of angiotensin-Ⅱ infusion and high salt diet.These suggest that the poor reproducibility of current modeling methods for uremic cardiomyopathy.Methods5/6 nephrectomy or modified nephrectomy were performed on male SD rats,and left ventricular morphology was dynamically observed by echocardiography.After the observation of cardiac hypertrophy,the tissue samples were taken and the renal function was tested to compare these two methods on uremic cardiomyopathy model establishment.Modified nephrectomy was performed on female SD rats,and left ventricular morphology was dynamically observed by echocardiography.After the observation of cardiac hypertrophy,the tissue samples were taken and the renal function was tested to analyze whether this method is suitable for uremic cardiomyopathy model establishment in female rats.Modified nephrectomy was performed on male C57BL/6,BALB/c and CD-1 mice,and left ventricular morphology was dynamically observed by echocardiography.After the observation of cardiac hypertrophy,the tissue samples were taken and the renal function was tested to analyze whether is suitable for uremic cardiomyopathy model establishment in these common strains.Female mice were selected to further analyze whether this method can be used to construct uremic cardiomyopathy model.Male CD-1 mice were fed with adenine contained-diet to explore a suitable feeding method for constructing CKD model.The left ventricular morphology was dynamically observed by echocardiography,and tissue samples were taken after observation of cardiac hypertrophy.Renal function was detected to confirm the successful construction of uremic cardiomyopathy model.Based on feeding methods for male CD-1 mice,adenine contained-diet was used to investigate an appropriate feeding method for the establishment of uremic cardiomyopathy model in female CD-1 mice.The left ventricular morphology was dynamically observed by echocardiography,and tissues samples were taken after the observation of cardiac hypertrophy.Renal function was detected to confirm the successful construction of uremic cardiomyopathy model.Results and discussion 5/6 nephrectomy results in uremic cardiomyopathy in male SD rats at 12th week after surgery,while modified nephrectomy only takes 5 weeks and the mortality of the modified nephrectomy is slightly higher than that of 5/6 nephrectomy.Meanwhile,this method can also induce uremic cardiomyopathy in female SD rats at 5th week after surgery.Modified nephrectomy fails to induce uremic cardiomyopathy in male C57BL/6 and BALB/c mice within 12 weeks,which only show mild renal injury.Modified nephrectomy can induce obvious uremic cardiomyopathy in CD-1 mice at 5th week after surgery.Similarly,uremic cardiomyopathy is observed in female CD-1 mice at 5th week after surgery as well.5-week 0.25%adenine contained-diet and 4-week normal diet cause uremic cardiomyopathy in male CD-1 mice,whereas 5-week 0.3%adenine contained-diet and 2-week normal diet are needed to induce uremic cardiomyopathy in female CD-1 mice.