Multi-targeting Action Mechanism of Wenyang Xiaoyin Prescription on Doxorubicin-induced Mouse with Chronic Heart Failure Based on NF-κB/AVP-AQP2 Complex Pathway Mediated by Liver X Receptor
10.13422/j.cnki.syfjx.20250313
- VernacularTitle:基于肝X受体介导NF-κB/AVP-AQP2复合通路的温阳消饮方抗阿霉素诱导慢性心力衰竭小鼠多靶向作用机制
- Author:
Baixue LI
1
;
Junfeng ZHAO
2
;
Song ZHANG
3
;
Lei LIU
3
;
Yangzhi PENG
1
;
Hang ZHOU
1
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine（TCM）， Chengdu 611137，China
2. Chengdu Pidu District People's Hospital， Chengdu 611730，China
3. Affiliated Hospital of Chengdu University of TCM， Chengdu 610072，China
- Publication Type:Journal Article
- Keywords:
Wenyang Xiaoyin prescription;
chronic heart failure;
liver X receptor;
arginine vasopressin （AVP）-vasopressin V2 receptor （V2R）-aquaporin 2 （AQP2） signaling pathway;
nuclear transcription factor （NF）-κB signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(14):286-297
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the therapeutic effects of Wenyang Xiaoyin Prescription （Linggui Zhugan Tang combined with Tingli Dazao Xiefei Tang） on a doxorubicin-induced mouse model of chronic heart failure （CHF）. The multi-targeting action mechanism of the therapy is revealed， based on the arginine vasopressin （AVP）-vasopressin V2 receptor （V2R）-aquaporin 2 （AQP2） signaling pathway and nuclear transcription factor -κB （NF-κB） pathway mediated by the liver X receptor （LXR） in the heart， brain， and kidney tissue. MethodsCHF mouse models were established by using intraperitoneal injection of doxorubicin and subsequently divided into a blank control group， a model control group， Wenyang Xiaoyin Prescription groups （Linggui Zhugan decoction combined with Tingli Dazao Xiefei decoction） with various doses， a captopril group， and a combination group receiving both Wenyang Xiaoyin prescription （as before） and captopril. Cardiac function was assessed by using color Doppler echocardiography， while the levels of brain natriuretic peptide （BNP）， AVP， and the renin-angiotensin-aldosterone system （RAAS） in the serum were measured via enzyme-linked immunosorbent assay （ELISA）. Pathological changes and ventricular remodeling in ventricular tissues were evaluated through hematoxylin and eosin （HE） and Masson staining， and myocardial cell apoptosis of mice was assessed by using TdT-mediated dUTP Nick-End Labeling （TUNEL） staining. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to detect the protein and RNA expression levels of LXRα， nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS） in the cardiac tissue， LXRβ， AVP in the hypothalamus， and LXRβ， V2R， and AQP2 in the kidneys. Furthermore， immunohistochemistry was used to quantify AQP2-positive collecting ducts in renal tissues. ResultsThe Wenyang Xiaoyin prescription significantly enhanced cardiac function indicators in CHF mice， reducing levels of BNP， AVP， and RAAS in the serum. It also mitigated myocardial cell damage and fibrosis change. The Wenyang Xiaoyin prescription inhibited the expressions of NF-κB and its downstream targets TNF-α and iNOS and improved myocardial inflammatory response， cell apoptosis， and ventricular remodeling by upregulating the expression of LXRα in cardiac tissues. Concurrently， the Wenyang Xiaoyin prescription elevated LXRβ expression in the kidneys and hypothalamus while downregulating the expression levels of AVP， V2R， and AQP2， as well as water permeability in the collecting ducts， thereby alleviating cardiac load. ConclusionThe intervention of Wenyang Xiaoyin prescription demonstrates a significant therapeutic effect on CHF， and its role involves the multi-target effect mechanism of the AVP/V2R/AQP2 and NF-κB pathways mediated by the nuclear receptor LXR in the heart， brain， and kidney tissue.
