Effect of Cannabidiol on Pulmonary Fibrosis Analyzed by UPLC-Q-TOF-MS
10.13422/j.cnki.syfjx.20240662
- VernacularTitle:基于UPLC-Q-TOF-MS分析大麻二酚对肺纤维化的影响
- Author:
Mengdi SUN
1
;
Feiyu ZHANG
1
;
Huicong YANG
1
;
Yu WANG
1
;
Pingping CHEN
1
;
Fang LU
1
;
Shumin LIU
1
Author Information
1. Institute of Traditional Chinese Medicine,Heilongjiang University of Chinese Medicine, Harbin 150040,China
- Publication Type:Journal Article
- Keywords:
cannabidiol;
pulmonary fibrosis;
metabolomics;
inflammation;
immunity;
ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(12):185-193
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). MethodSD rats were randomly divided into blank group, model group, prednisone group(3.15 mg·kg-1) and cannabidiol low, medium and high dose groups(12, 36, 108 mg·kg-1), with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin(5 mg·kg-1), which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of matrix metalloproteinase-7(MMP-7), type Ⅱ alveolar cell surface antigen(KL-6), pulmonary surfactant-associated protein A(SP-A) and SP-D in serum. The expression levels of type Ⅰ collagen(Col-Ⅰ) and fibronectin(FN) in lung tissues were detected by immunohistochemistry, and the expression of mucin 5 subtype AC(MUC5AC) was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis. ResultCompared with the blank group, there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group, the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group, the expressions of MMP-7, KL-6, SP-A and SP-D in serum of the model group were significantly increased(P<0.01), while the expressions of MMP-7, KL-6, SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group(P<0.05, P<0.01). Compared with the blank group, the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased, and the fluorescence intensity of MUC5AC was significantly increased(P<0.01). Compared with the model group, the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased(P<0.05, P<0.01), and the expression of MUC5AC was significantly decreased(P<0.01). Compared with the blank group, a total of 18 differential compounds were screened out in the model group, which could be used as potential biomarkers, and cannabidiol could call back 16 of them, mainly involving 4 metabolic pathways(linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, and niacin and niacinamide metabolism). Compared with the blank group, the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group(P<0.05, P<0.01), while the relative contents of 5,6-EET, L-tyrosine and niacinamide were significantly decreased(P<0.01). Compared with the model group, cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid, and significantly increase the relative contents of 5,6-EET, L-tyrosine and niacinamide(P<0.01). ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis, and its mechanism may be related to linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, niacin and niacinamide metabolism.