AS-Ⅳ Slows the Progression of Diabetic Nephropathy by Inhibitting mTORC1 and Enhancing Autophagic Flux
We investigated the effect of AS-Ⅳ on the progression of diabetic nephropathy (DN) in rats in-duced with streptozotocin ( STZ) and the underlying mechanism involving autophagy. Methods:Male SD rats were divided into normal control group ( Normal group) and diabetic nephropathy rats group,diabetic nephropathy rats treated with AS-Ⅳ ( AS-Ⅳ group) or 4-phenylbutyrate (PBA group) or rapamycin (RAPA group) or AS-Ⅳ plus bafilomycin A1 (AS-Ⅳ+BA group). After 8 weeks of treatment,the renal function and renal injury indicators were detected by HITACHI automatically,morphology change of kid-ney was examined by histological evaluation ( HE) and periodic acid-Schiff ( PAS),The express of LC3 Ⅱ/Ⅰ and p62 were tested to evaluate the autophagy activity,the phosphorylation level of mTOR,Raptor,and the main downstream signal targets of S6K1 and 4EBP were measured to evaluate the activity of mTOR1 signaling pathway. Results:AS-IV treated animals had less histological glo-merular injury. A remarkable restoration of impaired autophagy,as indicated by altered expression and activity of p62 and LC3 Ⅱ/Ⅰ,and significant suppressed the mTOR1 signal pathway activity,as evidenced by decreasing of phosphorylation of Raptor and mTOR,and the downstream targets of S6 kinase and eukaryotic initiation factor 4B. Inhibiting autophagic flux with bafilomycin A1 abolished the renoprotection effect of AS-IV under diabetes conditions. Conclusion:AS-Ⅳ attenuates the progression of DN,which is media-ted at least in part by inhibition of mTOR1,with increased autophagy flux.
Astragaloside ⅣDiabetic nephropathyAutophagyMammalian target of rapamycin
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