AdipoRon delays renal aging induced by D-gal in mice via activating the SIRT1 signaling pathway
10.3760/cma.j.issn.0254-9026.2024.12.014
- VernacularTitle:脂联素受体激动剂通过激活SIRT1信号通路延缓D-半乳糖诱导小鼠肾脏衰老
- Author:
Zongmin ZHANG
1
;
Jing LIANG
;
Shan HUANG
;
Guoli HE
;
Pei SHEN
;
Manhong ZHOU
Author Information
1. 遵义医科大学附属医院老年医学科，遵义 563000
- Publication Type:Journal Article
- Keywords:
AdipoRon;
D-gal;
Renal aging;
SIRT1 signaling pathway
- From:
Chinese Journal of Geriatrics
2024;43(12):1592-1598
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.
