Effects of quercetin on renal autophagy and interstitial fibrosis in diabetes mellitus

Abstract

To observe the effect of quercetin (Que) on renal autophagy level and renal interstitial fibrosis in the mice with diabetes mellitus (DM),and to discuss the possible mechanism. The wild-type C57BL/6 mice were randomly divided into 3 groups,including normal control (Normal) group, DM group and Que group (n = 9 in every groups). The diabetic mouse model was established by injection of streptozotocin. After 8 weeks of successful replication of the diabetic model,Que was given to the mice in Que group by continuous gavage for 12 weeks,and then the mice in each group were sacrificed to detect the relevant biochemical parameters. The pathological changes of the kidney tissues were observed by HE staining and Masson staining. The levels of the proteins related to autophagy,epithelial-mesenchymal transition(EMT)and fibrosis were determined by Western blot. The mRNA expression of collagen type IV (Col IV),α-smooth muscle actin(α-SMA)and E-cadherin were detected by real-time PCR. Compared with Normal group, fasting blood glucose (FBG), kidney index (KI),serum creatinine, 24-hour urinary albumin excretion rate and 24-hour urine total protein were remarkably increased in DM group (P < 0. 001). The results of HE and Masson staining indicated that renal tissue presented fibrosis in DM group. The protein levels of E-cadherin,beclin-1,microtubule-associated protein 1 light chain 3-II (LC3-II)/LC 3I ratio were reduced in DM group,while the levels of α-SMA,Col IV and Snail1 were increased (P < 0.001). After intervention with Que for 12 weeks,all the relevant biochemical parameters and KI were reduced (P < 0.001) except FBG (P > 0. 05), and renal fibrosis lesions were obviously alleviated. Compared with DM group,the protein levels of E-cadherin,beclin-1 and LC3-II were increased in Res group,but the protein expression levels of α-SMA,Col IV,Snail1 were reduced(P < 0. 001). Compared with DM group, the mRNA level of E-cadherin was increased in Que group, but the mRNA levels of Col IV and α-SMA were reduced (P < 0.001). Quercetin significantly inhibits EMT and reduces renal interstitial fibrosis in diabetic mice,and its mechanism may be related to the promotion of renal autophagy.