The Role Of Matrine In Diabetic Kidney Disease And Its Molecular Mechanism

Objective: Diabetic kidney disease(DKD)is the most common cause of chronic kidney disease(CKD)and end-stage renal disease(ESRD)in the world.Podocyte dysfunction caused by hyperglycemia is the main cause of renal function damage in diabetic kidney disease.Matrine(MT)is a natural alkaloid from plants,which is used as an adjuvant for cardiovascular complications,retinopathy and nephropathy caused by diabetes.However,the research on the treatment of diabetic kidney disease with MT is still insufficient,and the related theory is unclear.The aim of this study is to explore the role of MT in diabetic kidney disease and its possible molecular mechanism.Methods: Firstly,the mouse model of diabetic kidney disease was established by high fat diet(HFD)and streptozotocin(STZ).After the success of the model,MT was given intragastrically for 4 weeks.The body weight and fasting blood glucose of mice were measured periodically,and the urine of mice was collected to detect metabolism and renal function.Kidney samples were collected at the end of the experiment.Renal tissue injury was observed by HE staining,PAS staining and transmission electron microscope.PCR,Western blot and immunohistochemical techniques were used to detect protein and gene expression.Then the effect of MT on podocytes and its possible mechanism were further verified by Western blot and flow cytometry in the cell model of diabetic kidney disease caused by high glucose.Results: In the mouse model of diabetic kidney disease induced by HFD and STZ,MT treatment could significantly reduce the symptoms of diabetes,reduce the ratio of urinary protein to creatinine,down-regulate the expression of glomerular inflammatory mediators and improve glomerular injury.MT can reduce podocyte loss and podocyte morphological changes,which may be the key to improve renal function.Further studies in the cell model of diabetic kidney disease caused by high glucose showed that MT could up-regulate the expression of autophagy-related proteins LC3 II and Beclin-1,down-regulate the expression of p62,up-regulate the expression of apoptosis inhibitor protein Bcl2,and down-regulate the expression of apoptosis-promoting executive protein BAX.It is suggested that MT can regulate the expression of autophagy regulatory genes,enhance podocyte autophagy and reduce podocyte apoptosis.To evaluate the activity of PI3K/Akt / m TOR pathways,MT can inhibit PI3K/Akt /m TOR pathways,which may be the key to promoting autophagy.Conclusion: MT can improve podocyte injury,protect renal function and alleviate diabetic kidney disease.Moreover,the improving effect of MT on diabetic kidney disease is connected with its inhibition of m Tor pathway,enhancement of podocyte autophagy and reduction of podocyte apoptosis.This study provides a new experimental basis for further research and clinical application of MT.