Establishment Of A Mouse Model Of Renal Failure And Behavioral Study Of Uremia Cognitive Impairment

Part ?: Establishment of a Kidney Failure Model in MiceObjective:The research establishes a mouse model of chronic renal failure to lay a foundation for further exploring the pathogenesis of renal failure and the prevention and treatment of progression of end-stage renal failure.Methods:60 C57BL/6 male mice aged 6-8 weeks were randomly divided into four groups:normal group,sham-operated group,model group for 4W and model group for 8w.The left renal artery branch ligation and right nephrectomy were performed in the model group for 4 weeks and 8 weeks.In the sham-operated group,the mice were only performed the operation of skin and muscle incision and suture instead of kidney ligation and excision.Normal group: no treatment.After 8 weeks,blood pressure,urinary albumin / creatinine ratio(ACR),blood biochemical indexes and renal pathological changes were measured and recorded.Results:(1)Blood biochemical index: Compared with normal group and sham-operated group,mice in model group showed an increase in serum urea nitrogen [(19.86±3.37)mmol/l vs(8.45±0.95)mmol/l,P<0.01],serum creatinine [(37.91±3.11)?mol/l vs(25.19±4.98)?mol/l,P<0.01].blood concentration of phosphorus [(3.04±0.41)mmol/l vs(2.45±0.26)mmol/l,P<0.01],and a decrease in hemoglobin concentration[(114.42±20.45)g/L vs(137.10±6.77)g/L,P <0.01] after 4 weeks as shown in Table 2.There was no significant difference between 4-week model group and 8-week model group in this study.(2)Urinary ACR: Urinary ACR in model group is significantly higher than that in normal group and sham-operated group at 4w and 8w [(151.24±76.3)mg/g,(159.99±80.90)mg/g vs(14.57±2.39)mg/ g,(14.26 ± 2.46)mg / g(p < 0.01)].(3)Blood pressure: systolic blood pressure and diastolic blood pressure in model group of4 w and 8w were significantly higher than those in normal group and sham operation group [(117.24±4.18)/(78.97±3.98)mmHg,(121.30±4.92)/(73.70±6.29)mmHg vs(96.33 ± 4.51)/(55.71 ± 8.84)mmHg,(96.41 ± 5.02)/(54.31 ± 7.32)mmHg(p <0.01)].(4)Kidney pathology: The results showed glomerulosclerosis,renal tubular atrophy,renal interstitial fibrosis,small renal blood vessel incrassation,protein case,red blood cell case,local inflammation,and calcification,etc.Conclusion:The mouse model of chronic renal failure was established by ligation of left renal artery branch and right nephrectomy for the first time in China.The serum creatinine increased significantly 4 weeks after operation,accompanied with hypertension,proteinuria,anemia,hyperphosphatemia and other characteristics of chronic renal failure.In renal pathology,glomerular sclerosis,renal interstitial fibrosis and other end-stage renal disease manifestations could be seen,which showed that the model of renal failure was stable and good.Part ?: Behavioral Experimental Study on Cognitive Impairment in UremiaObjective:The research evaluates the learning and memory abilities of uremic mice by observing the performance of uremic mice in the Morris water maze experiment at different stages,so as to lay a foundation for further exploring the mechanism of cognitive impairment in chronic kidney disease.Methods:The mice of uremia 4w,uremia 8w,normal group and sham-operated group were tested by Morris water maze.The experiment included hidden platform experiment and space exploration experiment.The escape latency time and the number of times of crossing the platform were recorded respectively.Results:Compared with the normal group and sham-operated group,the escape latency time extended in the group of 8-week uremic mice in the hidden platform experiment,but the number of times of crossing the platform decreased in the space exploration experiment.The difference was statistically significant(p < 0.05),but there was no significant difference in the group of 4-week uremic mice.Conclusion:The learning and memory abilities of uremic 8-week mice decreased significantly in the Morris water maze experiment,which indicated that the model met an appropriate behavioral experimental node 8 weeks after the establishment of the model,providing a good time reference for the study of uremic cognitive impairment.