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Objective: To observe the effect of aldehyde scavenger, salicylamine (SAM), on atherosclerosis (AS) and its phenotype in uremic apolipoprotein E knockout (ApoE-/-) mice. Methods:Uremic ApoE-/- mice model was created by 5/6 nephrectomy; control ApoE-/- mice were sham-operated. Three subgroups of experimental mice were set up: uremia SAM intervention group, uremia group and control group, which were treated with SAM (1 g/L) or vehicle for 6 weeks, respectively. After the intervention was completed, we assessed the body weight, blood pressure, renal function, serum lipid profile, serum SAM concentration, extent and characteristic of aortic atherosclerotic lesion in each group of mice. Results: Compared with control group: aortic AS lesion area, necrotic area and macrophage content in AS lesion increased but collagen content in AS lesion decreased in uremia group. SAM treatment for 6 weeks lessened the atherosclerotic lesion area, necrotic area and macrophage content of plaques, and meanwhile increased collagen content of plaques in uremic mice, not accompanied by changes in body weight, blood pressure, serum lipid profile or renal function. SAM did not accumulate or induce toxic effect on uremic ApoE-/- mice. Conclusion: Aldehyde scavenger SAM ameliorates renal injury-induced acceleration of AS, alters atherosclerotic phenotype, and increases the stability of plaques. These benefits are independent of effects on blood pressure, lipid profile or renal function. SAM does not accumulate or induce toxic effect in uremic ApoE-/- mice.
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Objective To observe the effects of Hedan tablet on cytokines and oxidation factors in APOE-/-mouse, and to explore its effect on atherosclerosis and to explore its behind mechanism. Methods APOE-/-mice (n=50) were randomly divided into control group, model group, low dose Hedan tablet treatment group, high dose Hedan tablet treatment group and simvastatin treatment group. Mice in control group were given normal feed while mice in other groups were fed with high cho?lesterol diet. Hedan or Simvastatin was administrated intra-gastrically while normal saline was given to model group in the same route. After 12 weeks, mice were sacrificed to observe the mRNA level of tumor necrosis factor-α(TNF-αmRNA) in aorta by RT-PCR. Mean while, serum levels of interleukin-1 (IL-1), interleukin-10 (IL-10), malonaldehyde (MDA) and su?peroxide dismutase (SOD) were determined in different groups. Results Compared with control group, TNF-αmRNA tran?scription level as well as serum levels of IL-1 and MDA significantly increase while serum levels of IL-10 and SOD de?creased remarkably in model group, (P<0.01). Compared with model group, mRNA levels of TNF-αas well as serum levels of IL-1 and MDA were significantly decreased while serum levels of IL-10, SOD were greatly increased in low dose and high dose Hedan tablet treatment groups as well as in simvastatin treatment group (P<0.01). Conclusion Hedan tablet inhibit the formation of atherosclerosis through its anti-oxidation role and anti-inflammation role.
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Background Dyslipidemia is one of the major causes of age-related macular degeneration (AMD).At present,the study of the preventive and treating methods of A MD is still a hot spot.Objective The purpose of this study was to observe the effect of tonifying the spleen and promoting blood circulation on the retina and Bruch membrane in apolipoprotein E-deficient (ApoE-/-) mice with dyslipidemia.Methods Thirty-six ApoE-/-mice aged 2 months were randomly divided into the normal diet group,high fat diet group and medicine group.A diet with a higher content of fat was given for 5 consecutive months to the mice of the high fat diet group and medicine group,and in the last month,a concoction that tonifies the spleen and promotes blood circulation was gavagely administered in the medicine group,and an equivalent volumes of normal saline solution was administered in the same way in the normal diet group and high fat diet group.Total plasma cholesterol (TC),low density lipoprotein (LDL)and triglyceride (TG) were detected by (ELISA? Name of assay?) using the 7170 Hitachi automatic biochemical analyzer,and morphological changes of the retina and Bruch membrane were examined by light microscopy and transmission electron microscopy.The number of outer nuclear layer (ONL) cells,retinal pigment epithelial (RPE) cells and the thickness of the Bruch membrane were examined by semi-quantitative histopathology with the Mias 2000 Imaging Analyzer System.Results The concentrations of TC,LDL and TG were (6.47 ±0.49) mmol/L,(1.46 ±0.10)mmol/L and (0.62 ±0.21) mmol/L,respectively,in 7-month-old mice of the medicine group,showing a significant reduction in comparison with (10.53 ±0.30) mmol/L,(1.90±0.13) mmol/L,(1.15±0.29) mmol/L of the high fat diet group,and (9.63 ± 0.18) mmol/L,(1.12 ± 0.15) mmol/L,(0.88 ± 0.21) mmol/L in the normal diet group (P＜0.05-0.01).The disorder and atrophy of ONL and RPE cells,divergence of fiber of the Bruch membranes were found in both the high fat diet group and normal diet control group under the light microscope,and drusen formed in some of the mice in the high fat diet group.However,ONL and RPE were well organized in the medicine group.The cell numbers in the ONL and RPE layer in the 7-month-old mice were (23 124.00±755.18) and (10.75±0.59),respectively,in the medicine group,(19 107.00 ± 1436.82) and (8.55 ± 1.11),respectively,in the high fat diet group,(21 663.00± 1073.27) and (9.75 ±0.58),respectively,in the normal diet group,with significant differences among them (P＜0.05-0.001).Thickness of the Bruch membrane in the medicine group extensively reduced in high fat diet group and normal diet control group (P＜0.01).The ultrastructures of the RPE and Bruch membrane were much more improved in the mdedicine group.Conclusions Tonifying the spleen and promoting blood circulation can attenuate hyperlipemia in ApoE-/-mouse;furthermore,it lessens the pathological abnormalities in the ONL,RPE and Bruch membrane.
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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; moreover, 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.
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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.