Metabonomic Analysis of Wenfei Huaxian Granules Against Idiopathic Pulmonary Fibrosis in Mice
10.13422/j.cnki.syfjx.20220849
- VernacularTitle:温肺化纤颗粒抗小鼠特发性肺纤维化的代谢组学分析
- Author:
Shanshan LI
1
;
Jun HUANG
1
;
Longxue LI
1
;
Shaofeng LI
2
;
Cheng ZHANG
2
;
Xiao YU
1
;
Yuanbing ZHANG
2
Author Information
1. Laboratory Animal Science and Technology Center，School of Traditional Chinese Medicine， School of Pharmacy，Jiangxi University of Chinese Medicine，Nanchang 330004，China
2. The Affiliated Hospital of Jiangxi University of Chinese Medicine，Nanchang 330006，China
- Publication Type:Journal Article
- Keywords:
Wenfei Huaxian granules;
idiopathic pulmonary fibrosis（IPF）;
metabolomics;
bleomycin sulfate;
ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）;
inflammatory factors;
oxidative stress
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(9):166-178
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate（BLM）-induced pulmonary fibrosis modeling and administration， and the mechanism of Wenfei Huaxian granules（WHG）against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group， control group of 14 days， model group， model group of 14 days， low-dose WHG group and high-dose WHG group. BLM（0.04 U per mouse）was injected into the trachea of mice in the model group， model group of 14 days， low-dose WHG group and high-dose WHG group， and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM， and mice of control group， control group of 14 days， model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days， and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid（BALF）was collected for leucocyte differential count， the pathological examination and hydroxyproline（HYP）content determination of lung tissues of mice were performed， and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA）were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group， a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group， the alveolitis score， fibrosis degree score and HYP content increased significantly（P<0.01）， and the total number of leukocytes， macrophages and lymphocytes in BALF increased significantly（P<0.05）. A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days， mainly lipid metabolites， which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites， mainly amino acid metabolites， were screened between the control group and model group， mainly involving nucleic acid damage and inflammatory process. Compared with the model group， the HYP content， fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly（P<0.05， P<0.01）， and the total number of lymphocytes in BALF decreased significantly（P<0.05）. Compared with the model group， 27， 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group， which mainly involved in the metabolic pathways of inflammation related lipids metabolism， arginine and tryptophan metabolism， and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis， collagen deposition and inflammatory reaction in mice， and its anti-fibrotic effect may be related to the adjusting of inflammatory factors， nitric oxide and oxidative stress related metabolic pathways.
