Establishment of a uremic apolipoprotein E knockout mouse model to explore the mechanism of uremic atherosclerosis / 药物分析学报

ABSTRACT

Objective To establish a uremic apoE-/- mouse model to observe serum biochemical parameters and features of aortic root atherosclerosis (AS) in the model. Methods A uremic model was induced surgically in apoE-/- mice electrocautery of the right kidney at 8 weeks of age and nephrectomy (NX) of the left one 2 weeks later. Control mice were sham-operated. Two weeks after NX, renal functions were detected in the uremic and control mice to evaluate the efficiency of the model. After 10 weeks of NX, blood samples were taken to determine serum biochemical parameters, and aortic root was collected for frozen sections to investigate the lesion features of AS. Results Two weeks after NX, renal functions declined significantly in the uremic mice compared with the control ones, and remained stable 8 weeks later either in males or in females. Ten weeks after NX, serum levels of TCH, TG and LDL-C were dramatically higher in the uremic mice than in the controls, whereas no differences in serum HDL-C or glucose concentration were found between the two groups. Aortic root plaque relative area increased significantly in the uremic mice compared with the controls either in males or in females; more-over, the lesion area was larger in female mice than in male ones. Conclusion We established a uremic apoE-/- mouse model successfully, and this model is characterized by accelerated atherogenesis which is associated with an increase in serum lipid profile. This experimental model can be a useful tool to study the pathogenesis and therapeutic strategies of uremic AS.