Mechanism of Huazhuo Jiedu Prescription in Alleviating Renal Fibrosis in 5/6 Nephrectomy Rats Based on AMPK/mTOR Pathway
10.13422/j.cnki.syfjx.20250638
- VernacularTitle:基于AMPK/mTOR通路探讨化浊解毒方减轻5/6肾切除大鼠肾纤维化的作用机制
- Author:
Wanqing WANG
1
;
Yashi WANG
1
;
Hui GAO
1
;
Linlin ZHENG
2
;
Dong BIAN
2
;
Cun FENG
2
;
Xiaona WEI
1
Author Information
1. Graduate School of Hebei University of Chinese Medicine， Shijiazhuang 050091， China
2. The First Affiliated Hospital of Hebei University of Chinese Medicine/Hebei Provincial Hospital of Traditional Chinese Medicine， Shijiazhuang 050011， China
- Publication Type:Journal Article
- Keywords:
Huazhuo Jiedu prescription;
renal fibrosis;
autophagy;
AMP-activated protein kinases;
mammalian target of rapamycin
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(22):90-97
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveBased on the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway， this study aimed to observe the effect of the Huazhuo Jiedu prescription on renal fibrosis in 5/6 nephrectomy rats and explore its underlying mechanism. MethodsA total of 67 SPF-grade male SD rats were used， of which 11 were randomly selected as the normal group. A chronic renal failure （CRF） model was established using 5/6 nephrectomy. The successfully modeled rats were randomly assigned to the model group， losartan potassium group （4.5 mg·kg-1）， and low- （1.175 g·kg-1）， medium- （2.35 g·kg-1） and high-dose （4.7 g·kg-1） Huazhuo Jiedu prescription groups， with 9 rats per group. Each group received an equivalent volume of saline or the corresponding concentration of Huazhuo Jiedu prescription by gavage once daily for 8 weeks. Hematoxylin-eosin （HE） and Masson staining were used to observe renal tissue pathological changes. Transmission electron microscopy examined renal ultrastructure. Immunohistochemistry （IHC） detected expressions of α-smooth muscle actin （α-SMA） and transforming growth factor-β1 （TGF-β1）. Western blot analyzed expression levels of microtubule-associated protein Ⅰ light chain 3Ⅱ （LC3Ⅱ）， Beclin1， p62， AMPK， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultsCompared with the normal group， the model group exhibited glomerular shrinkage， mesangial and interstitial thickening， and tubular vacuolar degeneration， with no evident autophagosomes or autophagolysosome structures. Expression levels of α-SMA and TGF-β1 were significantly increased （P0.01）， while p-AMPK/AMPK， Beclin1， and LC3Ⅱ were significantly decreased （P0.01）， and p-mTOR/mTOR and p62 were significantly increased （P0.01）. Compared with the model group， the medium- and high-dose Huazhuo Jiedu prescription groups and the losartan potassium group showed varying degrees of pathological improvement. Autophagosomes with double- or multiple-layer membranes and autophagolysosomes with monolayer membranes containing undegraded organelles were observed. Renal α-SMA and TGF-β1 protein expression levels were markedly reduced （P0.05， P0.01）， p-mTOR/mTOR and p62 were significantly decreased （P0.05， P0.01）， and p-AMPK/AMPK， Beclin1， and LC3Ⅱ expression levels were significantly increased （P0.05， P0.01）. ConclusionHuazhuo Jiedu prescription may improve renal fibrosis in 5/6 nephrectomy rats by regulating the AMPK/mTOR signaling pathway and enhancing autophagy.
