Evaluation Of The Protective Effect Of Celastrol On Early Kidney Injury In Diabetic Rats Using ^99mTc-DTPA Renal Dynamic Imaging

Objective:Diabetes can cause kidney damage in the early stages of the disease and eventually develop into Diabetic Nephropathy（DN）as the disease progresses.Diabetic nephropathy is an important cause of end-stage renal disease because its onset is insidious and difficult to detect in the early stages.It has been found that Celastrol can protect the kidney and improve renal function in the early stage of diabetes,but the evaluation of its efficacy by SPECT renal dynamic imaging is unclear.We evaluated the effect of Celastrol on early renal function in type 2 diabetic rats（DM）by SPECT.Methods:After successful modeling of healthy male Sprague-Dawley（SD）rats,the rats were divided into Normal control group（NC）,Diabetic model group（DM）,Diabetic model+low-dose celastrol group（DM+LC）,Diabetic model+high-dose celastrol group（DM+HC）,after 3 weeks of intervention.^99mTc-DTPA SPECT renal dynamic imaging was performed to detect the glomerular filtration rate（GFR）,and the kidney tissues were obtained from the execution and biochemical indexes were obtained,and the kidney tissues were preserved in HE staining and Masson staining.The pathological morphological changes were observed under light microscope after HE staining and Masson staining in each group of rats.Results:1.General condition and biological behavior of rats:During the experimental period,the NC group rats were in good mental condition,responsive,with dry and shiny hair,normal development,normal feeding,drinking and urination.The rats in each DM group were in a slightly poorer mental state,with slow response,damp,dark yellow hair,lethargy,excessive drinking,polyphagia and polyuria.2.Body weight and renal index:At the end of the 3rd week of the experiment,compared with the NC group,the rats in the DM group had significantly reduced body weight（P<0.05）;compared with the DM group,the DM+HC group had significantly reduced body weight（P<0.05）.Compared with the DM group,the DM+HC group showed a significant decrease in body weight（P<0.05）,and the DM+LC group showed no statistical difference in body weight.Compared with the DM group,there was no statistically significant difference in renal index between DM+LC group and DM+HC group.3.Blood glucose,blood lipids and renal biochemical indexes:compared with the NC group,blood urea nitrogen（BUN）was significantly increased in the DM group（P<0.05）;compared with the DM group,there was no statistically significant difference in the drug intervention group（DM+LC group and DM+HC group）;compared with the DM group,there was no statistically significant difference in the drug intervention group（DM+LC group and DM+HC group）.The immediate blood glucose,blood creatinine（SCr）,serum low-density lipoprotein（LDL）,serum high-density lipoprotein（HDL）,total cholesterol（TC）,and triglyceride（TG）levels in the DM group were not significantly different from those in the DM group（DM+LC and DM+HC groups）.The effect of ryanodine on renal histomorphology of diabetic rats:the glomerular volume was normal in the NC group,capillary collaterals were clear,the thylakoid matrix and endothelial cells were not hyperplastic,the renal tubules were normal,the renal interstitium was rarely infiltrated by inflammatory cells,and the renal glomeruli were normal.In the DM group,the glomerular volume was significantly increased,the capillary collaterals were swollen,the thylakoid matrix was proliferated,the endothelial cells were enlarged,the tubules were enlarged,the interstitium was infiltrated with inflammatory cells,and the glomeruli were infiltrated with collagen fibers;in the DM+LC and DM+HC groups,the above conditions were improved to different degrees under the microscope.Conclusion:The therapeutic effect of celastrol on the kidney of early DM rats was found to be relatively sensitive by SPECT renal dynamic imaging,which can be used as a routine test.