Exploring the Mechanism of Pinggan Yishen Decoction Against Target Organ Damage in Spontaneously Hypertensive Rats Based on UPLC-Q-TOF/MS and Network Pharmacology
10.14148/j.issn.1672-0482.2024.0949
- VernacularTitle:基于UPLC-Q-TOF/MS整合网络药理学探讨平肝益肾方治疗自发性高血压大鼠靶器官损害的效应机制
- Author:
Weiting ZHANG
1
,
2
,
3
;
Qiong WANG
;
Yadong FAN
;
Huihui WANG
;
Shanshan CHEN
;
Siqi ZHANG
;
Yiying CHEN
;
Lei WU
;
Guoliang DAI
;
Bingbing SONG
;
Zhuyuan FANG
Author Information
1. 南京中医药大学附属医院,江苏 南京 210029
2. 江苏省中医院高血压研究所,江苏 南京 210001
3. 江苏省中医院高血压病临床医学创新中心,江苏 南京 210019
- Keywords:
Pinggan Yishen Decoction;
hypertension;
target organ damage;
UPLC-Q-TOF/MS;
network pharmacology
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2024;40(9):949-961
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.
