天津中医药大学学报2025，Vol.44Issue(6)：512-518,7.DOI:10.11656/j.issn.1673-9043.2025.06.06
SIRT1-PGC-1α-NRF2通路探讨金樱子多糖介导氧化应激改善糖尿病肾脏病的作用机制
Exploring the Mechanisms of Rosa laevigata polysaccharides in Treating Diabetic Kidney Disease Based on the SIRT1-PGC-1α-NRF2 Signaling Pathway through Oxidative Stress
摘要
Abstract
[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.关键词
糖尿病肾脏病/金樱子多糖/沉默调节蛋白1/过氧化物酶体增殖物激活受体γ共激活因子1α/核因子类红细胞相关因子2/氧化应激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分类
医药卫生引用本文复制引用
孙文娟,李玉玲,佟晴晴,潘保朝,张天宇,苏秀海,郭煊..SIRT1-PGC-1α-NRF2通路探讨金樱子多糖介导氧化应激改善糖尿病肾脏病的作用机制[J].天津中医药大学学报,2025,44(6):512-518,7.基金项目
河北省中医药管理局科研计划项目(2024488) （2024488）
苏秀海全国名老中医药专家传承工作室项目(国中医药人教函[2022]75 号). （国中医药人教函[2022]75 号）
