HuangQi Decoction Improves Glomerular Injury Mediated By Autophagy Regulation Through Activating AMPK/mTOR Signaling Pathway In ApoE^-/- Diabetic Nephropathy Mice

Objective:The animal model of diabetic nephropathy was established to explore the renal protective effect of Huangqi decoction（HQD）on STZ-induced diabetic nephropathy ApoE^-/-mice and the specific mechanism.Methods:8 weeks old male ApoE^-/-mice were intraperitoneally injected with streptozotocin（55mg/kg）for 5 consecutive days.Two weeks later,blood glucose>15 mmol/L mice were considered successful.The successful mice were randomly divided into 5 groups:normal group,model group,model+HQD group,model+Compound C group and model+HQD+Compound C group,all mice were sacrificed after 8 weeks of intragastric administration of HQD,Compound C was administered intraperitoneally two weeks before sacrifice.Serum and kidney samples were taken at the time of sacrifice,and the general parameters,renal function indexes and pathological changes of kidney tissues were detected in each group,Western blot and immunofluorescence were used to detect the protein expression of AMPK/m TOR and autophagy-related signaling pathway.Results:1.HQD significantly improved the general parameters of diabetes mice（body weight,blood glucose and 24h urine volume etc.）,reduced ACR and relieved kidney inflammation,and alleviated renal pathological damages caused by DN..2.HQD inhibited the over-activation of m TOR by up-regulating AMPK expression and activate the downstream autophagy signaling pathway,which can express the expression of autophagy-related proteins ULK1,LC3II and Beclin-1,and decrease the expression of p62 and p-m TOR,thereby improving autophagy to protect the glomerulus and delay the development of DN.Conclusion:1.HQD can improve the body weight,blood glucose,daily water intake and 24h urine volume of DN mice,and reduce proteinuria,BUN and serum creatinine,and alleviating kidney inflammation.These effects are related to the AMPK/m TOR signaling pathway;2.HQD can improve glomerular injury caused by diabetic nephropathy by up-regulating AMPK expression and regulating autophagy,thereby alleviating the progression of DN.