Effect of Qigui Didang Decoction in Improving Metabolic Memory of Diabetic Nephropathy Through Sirt1/p53/NF-κB p65 Pathway
10.13422/j.cnki.syfjx.20251105
- VernacularTitle:芪归抵挡汤通过Sirt1/p53/NF-κB p65途径改善糖尿病肾病代谢记忆效应
- Author:
Tingting HU
1
;
Lifei FAN
1
;
Yuqin GUO
1
;
Min LIN
1
Author Information
1. Fujian University of Traditional Chinese Medicine，Fuzhou 350122，China
- Publication Type:Journal Article
- Keywords:
diabetic nephropathy;
metabolic memory;
silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65;
method of tonifying deficiency and unblocking collateral;
Qigui Didang decoction
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(18):20-29
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect and mechanism of Qigui Didang decoction， formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals， on improving metabolic memory of db/db mice with diabetic nephropathy （DN） through silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65 pathway. MethodsFifteen db/db mice were randomly divided into model group （10 mL·kg-1·d-1）， resveratrol group （20 mg·kg-1·d-1）， and Qigui Didang decoction group （3.34 g·kg-1·d-1） Another five db/m mice were selected as the normal group （10 mL·kg-1·d-1）. After the intervention， the kidney weight of each group was measured， and the kidney index （KI） was calculated. Fasting blood glucose （FBG）， creatinine （CRE）， β2-microglobulin （β2-MG）， blood urea nitrogen （BUN）， and cystatin C （CysC） were measured. Renal pathology was observed by hematoxylin-eosin （HE） staining and Masson staining. The mRNA and protein expression levels of Sirt1， NF-κB， tumor suppressor gene p53， interleukin-1β （IL-1β）， and cysteine aspartate protease-3 （Caspase-3） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered renal structure， obvious renal damage， and markedly elevated levels of renal function indexes （CRE， β2-MG， BUN， and CysC） （P<0.01）. The KI and blood glucose were significantly increased （P<0.01）， while Sirt1 expression was markedly decreased （P<0.01）. Expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were increased significantly （P<0.05）. Compared with those in the model group， DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG， improved renal function， and markedly decreased KI （P<0.01）， along with reduced CRE， β2-MG， BUN， and CysC levels （P<0.05）. Protein expression of Sirt1 was significantly upregulated （P<0.05）， while that of NF-κB p65， p53， IL-1β， and Caspase-3 was markedly decreased （P<0.05）. The mRNA expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were significantly decreased （P<0.05）. The staining results indicate improved renal fibrosis， significantly decreased fiber deposition （P<0.05）， and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN， thereby inhibiting renal cell apoptosis and inflammatory response in mice， and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.
