| Background:Diabetic kidney disease(DKD)is the most important microvascular complication of diabetes mellitus.The disease is not only a major cause of chronic kidney failure and end-stage kidney disease,but also an independent risk factor for cardiovascular disease.lt has become a public health issue of increasing concern worldwide.At present,the treatment of DKD is mainly for the control of blood glucose,blood pressure and proteinuria.Although these treatments can relieve symptoms and delay the development of end-stage renal failure,they cannot effectively control its development.Therefore,it is necessary to seek safe and effective treatment methods and traditional Chinese medicine.Objectives:To observe the effect on Yunpiheluo decoction(YPHL)on renal injury in ZDF rats and to explore the mechanism from the perspective of Sirtl/AMPK.So as to provide new ideas and experimental basis for the prevention and treatment of kidney injury in diabetes mellitus.Methods:1.Modeling:Male Zucker diabetic fatty(ZDF)rats(n=30)and ZL rats(n=10)for 8 weeks.The ZDF rats were fed withhigh-fat and high-sugar diet for 4 weeks,the ZL rats were fed with normal diet throughout the whole process.Fasting blood glucose was detected for 4 consecutive weeks,and the fasting blood glucose value was>7.8mmol/L after 4 weeks,which was a diabetic rat model.The model rats continued to be fed withhigh-fat and high-sugar diet.2.Model rats were randomly divided into model group,sirt1 strengthening group,YPHL group,and metformin group.ZL rats were used as normal control.3.Drug intervention:rats in the sirt1 strengthening group were initially injected with recombinant adenovirus Ad-SIRT1 through the tail vein.Rats in the YPHL group,12.5g/kg·d gavage was given to Yunpiheluo decoction.Metformin group was given Merformin Hydrochloride 0.15g/kg·d by gavage.Rats of normal control group,model group and sirt1 strengthening group were given 4 mL distilled water daily.Rats in each group were gavaged once a day for 10 weeks.4.Urine and blood were collected for renal function detection.In addition,the renal pathological changes were observed under light microscope with HE and Masson staining.the mRNA expression of Sirtl and AMPK were analyzed by real-time PCR.The protein levels of SIRT1,AMPK,p-AMPK,Drp-1,LC3,P62 and Parkin in the renal tissues wene determined by Western blot.Results:?Compared with control group,the rats in the model group were obviously obese,with dry and dull coat,severe depilation,lazy activities,no struggle in intragastasis,excessive urine,and loose stool.Fasting blood glucose(FBG),renal function related indicators namely urine protein(UP),urine microprotein(u-alb)and blood creatinine(Scr)were obviously increased(P<0.01).The mRNA expression of Sirt1 and AMPK were decreased(P<0.05).The protein levels of SIRT1,AMPK,p-AMPK,Parkin and LC3 were decreased(P<0.01)),P62 and Drp-1 were increased(P<0.05).Glomerular focal fibrosis,focal renal tubular epithelial cell vacuolation,necrosis,shedding and atrophy,tubular type,partial renal tubules dilated and renal interstitial fibrosis were observed,thickening of the wall of the arterioles.?The general condition of ZDF rats improved significantly after yunpiheluo decoction 1 treatment.Renal function improved,Scr and U-ALB were decreased(P<0.05),the mRNA expression of Sirtl and AMPK were increased(P<0.05),the protein levels of SIRT1,AMPK,p-AMPK,Parkin and LC3 were increased(P<0.01),P62 and Drp-1 were decreased(P<0.05).Kidney disease change also has obvious alleviate.Conclusion:?ZDF rats showed impaired renal function during early stage.?After yunpiheluo decoction 1 treatment,the degree of kidney disease is alleviated,which has a protective effect on the kidney.?Yunpiheluo decoction may protect the kidney of ZDF rats by activating Sirtl/AMPK signaling pathway,and regulating autophagy. |
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