NMN在糖尿病肾病大鼠肾脏纤维化中的作用及其机制

doi:10.13481/j.1671-587x.20180608

Abstract

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(Sirt1) 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 Sirt1, AKT, p-FoxO3a 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 μmol·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 Sirt1, AKT, and p-FoxO3a 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 Sirt1 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-FoxO3a 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 Sirt1 and AKT proteins in the HBZY-1 cells of the rats in 50 μmol·L^-1 NMN group were significantly increased (P<0.01), and the expression levels of Sirt1, AKT,and p-FoxO3a proteins in the HBZY-1 cells in 100 and 200 μmol·L^-1 NMN groups were increased significantly (P<0.05 or P<0.01).Conclusion: NMN can increase the expression levels of endogenous p-FoxO3a and Cav-1 proteins in the glomerular cells of the DN rats by regulating the expression levels of Sirt1 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.

Key words: diabetic nephropathy, nicotinamide mononucleotide, silent information regulator 1, protein kinase B, Forkhead box O3

CLC Number:

R363.1

CUI Qi, WANG Manyi, NONG Linlin, ZHAI Xiaoya, FENG Leping. Effect of NMN on renal fibrosis of diabetic nephropathy rats and its mechanism[J].Journal of Jilin University(Medicine Edition), 2018, 44(06): 1156-1162.

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Effect of NMN on renal fibrosis of diabetic nephropathy rats and its mechanism

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