ABSTRACT
Aim: To investigate the effect of Jinguishenqi decoction on renal podocyte autophagy in db/db diabetic mice and its mechanism. Methods: Twenty 6-week old db/db diabetic mice were randomly divided into four groups, with five mice in each group: saline group, Jinguishenqi decoction low dose group, Jinguishenqi decoction high dose group, metformin positive control group, and 5 male db/m mice as normal control group. The animals were sacrificed at 18 weeks old, and urinary albumin and creatinine were detected in 24 hours' urine. Blood glucose and creatinine were measured. The glomerular extracellular matrix proliferation in renal tissues was observed by PAS staining. The expression of WT1 in renal tissues was detected by immunohistochemistry, and autophagy in podocyte was observed by transmission electron microscopy. The protein expressions of LC I/II, p62, p-mTOR/mTOR and p-AMPK/AMPK in renal tissues were detected by Western blot. Results Compared with saline group of db/db diabetic mice, urinary albumin, urinary albumin/creatinine in 24 hours urine, serum creatinine and glomerular mesangial width all decreased after the treatment of Jinguishenqi decoction. Autophagosome in podocyte and the number of WT1 positive cell increased (P < 0. 05), and the expression of LC3 II in renal cortex decreased significantly (P < 0. 05) after the treatment of Jinguishenqi decoction. The phosphorylation of AMPK increased significantly (P < 0. 05) and the phosphorylation of mTOR was inhibited (P < 0. 05) after the treatment of Jinguishenqi decoction. Conclusions: Jinguishenqi decoction could promote autophagy, protect podocyte and delay the progression of diabetic nephropathy through AMPK-mTOR pathway.
ABSTRACT
Aim To investigate the effect of Jinguishenqi decoction on renal podocyte apoptosis in db/db diabetic mice and the underlying mechanism. Methods Six weeks old db/db diabetic mice were randomly divided into three groups; saline group, Jinguishenqi decoction group, metformin positive control group, and male db/m mice as normal control group. The animals were sacrificed at 18 weeks old, urinary albumin was detected in 24 hours urine, and blood glucose was measured. The glomerular mesangial proliferation was observed by PAS staining in renal tissues. The foot processes in podocyte were observed by transmission electron microscopy. The expression of podocin in renal tissues was detected by immunofluorescence. The protein expressions of caspase-3, p-Bcl-2, p-JNKl/JNKl in renal cortex were detected by Western blot. Results Compared with saline group of db/db diabetic mice, urinary albumin in 24 hours urine, foot process fusion and mesangial width were all reduced after the treatment of Jinguishenqi decoction. Podocin fluorescence in glomerular increased, and the expression of caspase-3 in renal cortex decreased significantlyafter the treatment of Jinguishenqi decoction (P < 0. 05) . The phosphorylation of JNK1 and Bcl-2 was inhibitedsignificantly after the treatment of Jinguishenqi decoction (P < 0. 05). Conclusions Jinguishenqi decoction could alleviate apoptosis of podocyte, protect podocyte and delay the progression of diabetic nephropathy through JNK1/Bcl-2 signaling pathway.