| Background: Diabetic Kidney Disease is an important microvascular complication of diabetes and a major cause of end-stage renal disease worldwide.Diabetic patients have obstacles to glucose uptake and utilization,and elevated free fatty acids in the blood.Adipocyte fatty acid-binding protein 4(FABP4)as a cytoplasmic partner of long-chain fatty acids,it plays an important role in maintaining the balance of glycolipids in the body,it is closely related to the occurrence and development of type2 diabetes and its complications.Forkhead box O1(FOXO1)is an important transcription factor that plays an important role in insulin resistance,pancreatic β-cell proliferation and differentiation,apoptosis,and glycolipid metabolism.This protein regulates FABP4 expression through nuclear translocation.Objective: In this study,we established a rat model of diabetic kidney disease to study the changes of FABP4 and FOXO1 expression in kidney tissues of rats with type 2 diabetic kidney disease and their correlation.Methods: Twelve SPF SD male rats were randomly divided into normal control group(giving ordinary basic diet),high-fat high-sugar diet + STZ group,single nephrectomy + high-fat high-sugar diet + STZ group,sham operation + high Fatty sugar diet + STZ group,three in each group.After 4 weeks of feeding,the fasting could not be stopped after 12 hours of weighing.The rats in the high-fat high-sugar group,the single nephrectomy group and the sham-operated group were given intraperitoneal injection of 1% STZ solution 30 mg/kg for 3 consecutive days.Group rats were given the same amount of sodium citrate buffer intraperitoneally.The blood glucose of the rats was measured 72 hours after the injection,and the non-fasting blood glucose was considered to be greater than 16.7 mmol/L and insulin resistance occurred,the type 2 diabetes model was successfully established.Continued feedingfor 8 weeks,with non-fasting blood glucose greater than 16.7mmol / L,urine volume greater than 150% of the original urine volume,24-hour urine protein quantitation greater than 30 mg / 24 h as a model for diabetic kidney disease.Rats were sacrificed after modeling,the jugular vein was used for blood creatinine,urea nitrogen,blood sugar and other indicators,the kidney tissue was weighed and the kidney hypertrophy index(kidney weight/weight x100%)was calculated,pathological sections were performed,and the expression of FABP4 and FOXO1 genes and proteins were detected by real-time PCR and Western blot,and correlation analysis was performed by pearson analysis.Results:(1)The rat model of type 2 diabetic kidney disease was successfully obtained.(2)The results of real-time PCR showed that compared with the normal control group,the expression levels of Fabp4 and Foxo1 in the kidney tissues of the high-fat high-sugar+STZ group,single nephrectomy+STZ group,sham operation+STZ group were increased.The expression of Fabp4 in the high-fat high-sugar + STZ group,single nephrectomy + STZ group,sham operation + STZ group was respectively 2.11 times(p>0.05),2.57 times(p<0.05),2.35 times of the normal control group(p>0.05).The expression levels of Foxo1 in the high-fat,high-sugar + STZ group,single nephrectomy + STZ group,and sham operation +STZ group was respectively 1.95 times(p>0.05),3.02 times(p<0.05),and 1.98 times of the normal control group(p>0.05).(3)Western blot was used to detect the protein expression of FABP4 and FOXO1 in the kidney tissues of each group.The protein expressions of FOXO1 and FABP4 in the kidneys of rats of of the high-fat and high-sugar group,single nephrectomy group and sham-operated group were lower than those in the normal control group,and the expression in the single nephrectomy group was significantly lower(p<0.05),the expression of the high-fat and high-sugar group and the sham-operated group was not significantly decreased(p>0.05)(4)Pearson correlation analysis showed that there was a significant positive correlation between Fabp4 and Foxo1 gene expression in the kidney tissues of normal control group,single nephrectomy and STZ group(p<0.05).There was no significant correlation between the high-fat high-sugar+STZ group and the sham-operated+STZgroup(p>0.05).Conclusion: The expression levels of Fabp4 and Foxo1 in renal tissue of type 2diabetic kidney disease rats were higher than normal control group.The gene expression level of Fabp4 and Foxo1 was positively correlated in the renal tissues of each group.The results of the study suggested that both Fabp4 and Foxo1 are involved in the development of type 2 diabetic kidney disease and both genes might be the potential new targets for the treatment of type 2 diabetic kidney disease. |
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