Effect of NMN on renal fibrosis of diabetic nephropathy rats and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective: To investigate the effect of niacinamide mononucleotide (NMN) on the fibrosis of renal cells in the rats with diabetic nephropathy (DN), and to elucidate the mechanism of NMN in regulating the fibrosis of renal parenchymal cells through silent information regulator 1 (Sirtl) and AKT pathways. Methods: The rat models of type 2 diabetes mellitus were induced by streptozotocin (STZ) and the model rats were randomly divided into experiment group (n= 30) and control group (n=10). The rats in experiment group were divided into diabetes + NMN group (n=15) and diabetes + PBS group (n=15). The rats in diabetes+ NMN group were given subcutaneous injection of NMN for 20 d and the rats in diabetes + PBS group were given 200 μL sterile PBS in the same way. Then the rats were decapitated and the kidney tissues were taken for section and protein extraction. The expression levels of Sirtl, AKT, p-Fox03a and Cav-1 proteins in kidney tissue of the rats in various groups were detected by Western blotting method and immuno-confocal focusing. The glomerular mesangial HBZY-1 cells were treated with high concentration of glucose (200 mmol · L-1) for 3-6 d, and then the cells were further randomly divided into 4 groups (treated with 0, 50, 100, and 200 mmol · L-1 NMN) and the cells only treated with 5. 6 mmol · L-1 glucose were regareded as control group. After 24 h culture, the cells were collected and the expression levels of Sirtl, AKT, and p-Fox03a proteins in the HBZY-1 cells in various groups were detected by Western blotting method. Results: Compared with diabetes +PBS group, the expression levels of Sirtl and AKT proteins in the renal parenchyma cells of the rats in diabetes+ NMN group were significantly increased (P<0. 01) and the expression levels of p-Fox03a and Cav-1 proteins in the renal parenchyma cells of the rats in diabetes + NMN group were also increased (P<0. 01). Compared with control group, the expression levels of Sirtl and AKT proteins in the HBZY-1 cells of the rats in 50 mmol · L-1 NMN group were significantly increased (P<0. 01), and the expression levels of Sirtl, AKT, and p-Fox03a proteins in the HBZY-1 cells in 100 and 200 mmol · L-1 NMN groups were increased significantly (P<0. 05 or P<0. 01). Conclusion: NMN can increase the expression levels of endogenous p-Fox03a and Cav-1 proteins in the glomerular cells of the DN rats by regulating the expression levels of Sirtl and AKT proteins, indicating that NMN and its analogues may play an important role in the prevention and treatment of the renal fibrosis of the DN rats.