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| Exploring the Mechanisms of Rosa laevigata polysaccharides in Treating Diabetic Kidney Disease Based on the SIRT1-PGC-1α-NRF2 Signaling Pathway through Oxidative Stress |
| Hits 420 Download times 266 Received:February 16, 2025 |
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| DOI
10.11656/j.issn.1673-9043.2025.06.06 |
| Key Words
diabetic kidney disease;Rosa laevigata polysaccharides;silencing regulatory protein 1;peroxisome proliferator-activated receptor gamma coactivator 1alpha;nuclear factor-like erythroid-associated factor 2;oxidative stress |
| Author Name | Affiliation | E-mail | | SUN Wenjuan | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | | | LI Yuling | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | 734883848@qq.com | | TONG Qingqing | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | | | PAN Baochao | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | | | ZHANG Tianyu | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | | | SU Xiuhai | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | | | GUO Xuan | Hebei Cangzhou Hospital of Integrated Chinese and Western Medicine, Cangzhou 061000, China | |
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| Abstract
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| [Objective] To investigate the effect of Rosa laevigata polysaccharides(RLP) in the treatment of diabetic kidney disease(DKD) and to explore its mechanism of action from the perspective of Silent regulator protein 1-peroxisome proliferator-activated receptor gamma coactivator 1 alpha-nuclear factor-like erythroid-associated factor 2(SIRT1-PGC-1α-NRF2) signaling pathway.[Methods] Sixty C57BL/6J mice were acclimatized and fed for 1 week, and all of them were given a high-sugar and high-fat diet for 8 weeks, except for 10 mice in the Control group(C), which were fed with basal chow, after which they were modeled with streptozotocin(STZ) and randomly and equally divided into a model group(M), a SIRT1 agonist group(S), a low-dose RLP group(RL), a medium-dose RLP group(RM), and a high-dose RLP group(RH). The mice were gavaged continuously for 8 weeks, and Fasting blood-glucose(FBG) and body weight were measured every 2 weeks in each group. After 8 weeks of treatment, 24h urine samples, blood samples, and kidneys of mice were collected for analysis and determination. Kits were used to determine 24h urine protein quantification(24 h-UPQ), Serum creatinine(Cr), blood urea nitrogen(BUN), and oxidative and antioxidant indices of renal tissues, superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and malondialdehyde(MDA), to assess the renal function and oxidative stress level in mice. Hematoxylin-eosin(HE) staining was performed on the same part of the kidneys to observe the pathological changes. Real-time fluorescence quantitative PCR(RT-qPCR) was used to detect silencing regulatory protein 1(Sirt1), peroxisome proliferator-activated receptor gamma coactivator 1alpha(Pgc-1alpha), nuclear factor-like erythroid-associated factor 2(Nrf2), heme oxygenase 1(HO-1), and NAD(P)H:quinone oxidoreductase 1(Nqo1) mRNA Expression. Western blotting detects SIRT1, PGC-1α, NRF2, HO-1, NQO1 protein expression.[Results] Compared with the model group, after treatment with SRT1720 and RLP, DKD mice showed a slower decrease in body mass, no difference in FBG, different degrees of reduction in 24 h-UPQ, Cr, BUN, different degrees of enhancement of SOD and GSH-Px activities, decrease in MDA content, different degrees of improvement in renal histopathological injury, and different degrees of increase in gene and protein expression levels of renal tissues SIRT1, PGC-1α, NRF2, HO-1, NQO1 protein expression levels corresponding gene were elevated to different degrees.[Conclusion] RLP may ameliorate kidney injury in DKD mice by activating the SIRT1-PGC-1α-NRF2 signaling pathway and inhibiting oxidative stress. |
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