Application of Avasimibe in preparation of medicine for treating pulmonary fibrosis
Avasimibe addresses the problem of alveolar macrophage foaming caused by PHMG inhalation exposure by targeting the SOAT1 enzyme, restoring cholesterol homeostasis and cell membrane fluidity, reducing foam cell formation, and effectively alleviating pulmonary fibrosis.
Patent Information
- Application Number
- CN202511188988.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-25
- Publication Date
- 2025-11-11
AI Technical Summary
Existing technologies have not elucidated the mechanism of alveolar macrophage foaming caused by polyhexamethylene guanidine (PHMG) inhalation exposure, and there is a lack of effective intervention targets to alleviate the progression of inhalation pulmonary fibrosis.
Avasimibe targets the SOAT1 enzyme, reduces the production of foam cells, restores cholesterol and cholesterol ester homeostasis, improves cell membrane fluidity, and restores lipophagus function, thereby alleviating the occurrence and development of pulmonary fibrosis.
Avasimibe significantly reduced foam cell formation, restored lipid metabolism balance, improved lung function, reduced extracellular matrix deposition, and effectively alleviated the progression of pulmonary fibrosis in in vitro and in vivo experiments.
Smart Images
Figure CN120919095A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of specific therapeutic activity technology of pharmaceutical preparations, and in particular to the use of Avasimibe in the preparation of drugs for treating pulmonary fibrosis. Background Technology
[0002] Pulmonary fibrosis is a complex lung disease involving multiple mechanisms, with its pathogenesis involving various pathophysiological changes such as epithelial-mesenchymal transition (EMT), oxidative stress, inflammatory activation, and endoplasmic reticulum stress. Alveolar macrophages, as the main target cells of exogenous chemical inhalation exposure, play a central role in lung injury caused by environmental pollutants. Polyhexamethylene guanidine (PHMG) is a broad-spectrum antibacterial agent, widely used as a humidifier disinfectant due to its colorless and odorless properties. In 2011, PHMG was identified as the main pathogen in a humidifier disinfectant-related lung injury outbreak in South Korea. Previous studies have shown that PHMG inhalation exposure can induce pulmonary fibrosis and alveolar macrophage foaming in mice. However, the mechanism of macrophage foaming in inhaled pulmonary fibrosis is not fully elucidated. Therefore, clarifying the specific mechanisms and identifying effective intervention targets has significant public health implications.
[0003] Acyl-CoA:cholesterolacyltransferase (ACAT / SOAT) is a key enzyme in mammals that catalyzes cholesterol esterification. It exists in two isoenzymes (ACAT1 / SOAT1 and ACAT2 / SOAT2), with SOAT1 being highly expressed in macrophages, epithelial cells, and steroid-producing cells and responsible for the conversion of cholesterol into cholesterol esters. Cholesterol, as a key component of mammalian cell membranes, not only participates in the regulation of membrane fluidity but is also a precursor to steroid hormones and bile acids. The body maintains its metabolic homeostasis through four pathways: cholesterol synthesis, uptake, efflux, and esterification. Disruption of this balance is closely related to cardiovascular diseases, neurodegenerative diseases, and malignant tumors.
[0004] Avasimibe, a specific SOAT1 inhibitor, has been proven safe for the treatment of atherosclerosis and has demonstrated significant efficacy in various tumor models. Avasimibe can improve the progression of certain diseases by altering cholesterol metabolism in tumor cells, thus affecting their growth and differentiation. However, whether avasimibe can improve the progression of inhaled pulmonary fibrosis remains unknown. Summary of the Invention
[0005] To address the aforementioned technical problems, the present invention aims to provide the application of Avasimibe in the preparation of drugs for treating pulmonary fibrosis. To achieve the above-mentioned objective, the present invention provides the following technical solution:
[0006] Application of Avasimibe in the preparation of drugs for treating pulmonary fibrosis.
[0007] Avasimibe reduces the production of foam cells by targeting SOAT1, thereby alleviating the development and progression of pulmonary fibrosis.
[0008] Avasimibe alleviates the development of pulmonary fibrosis by restoring the homeostasis of cholesterol and cholesterol esters.
[0009] Avasimibe alleviates the development of pulmonary fibrosis by improving the fluidity of cell membrane structures.
[0010] Avasimibe alleviates the development and progression of pulmonary fibrosis by restoring lipophage function.
[0011] The present invention also includes
[0012] PHMG inhalation exposure led to pulmonary fibrosis and foam cell formation in mice.
[0013] PHMG upregulates SOAT1 and disrupts cholesterol metabolism homeostasis.
[0014] Avasimibe targets and inhibits SOAT1 in an in vitro foam cell model.
[0015] Avasimibe restores altered lipid composition in an in vitro foam cell model.
[0016] Avasimibe restored the content and distribution of cholesterol and cholesterol esters in an in vitro foam cell model.
[0017] Avasimibe restored the fluidity of cell membrane structures in an in vitro foam cell model.
[0018] Avasimibe restored lipophage function in an in vitro foam cell model.
[0019] Avasimibe alleviated the formation of foam cells in vitro.
[0020] Avasimibe reduced PHMG-induced abnormal extracellular matrix deposition.
[0021] Avasimibe intervention restored general physical signs in mice, such as body weight, organ coefficients, and lung function.
[0022] Avasimibe intervention alleviated lipophage disorder in mouse lung tissue.
[0023] Avasimibe intervention reduced the formation of foam cells in bronchoalveolar lavage fluid in mice.
[0024] Avasimibe intervention improved the development of pulmonary fibrosis in mice.
[0025] The main advantages of this invention are: it reveals that Avasimibe can reduce the production of foam cells by targeting SOAT1, thereby alleviating the development and progression of pulmonary fibrosis. It also demonstrates that Avasimibe can restore cholesterol and cholesterol ester homeostasis, improve cell membrane fluidity, and restore lipophage function. This invention develops the application of Avasimibe in the treatment of pulmonary fibrosis. Attached Figure Description
[0026] Figure 1 To illustrate the effects of PHMG inhalation exposure on pulmonary fibrosis and lipid metabolism disorders in mice.
[0027] Figure A shows HE staining and Masson staining; Figure B shows co-localization staining of lipid droplets and macrophages in lung tissue; Figures C and D show transcriptome sequencing results; Figures E and F show SOAT1 detection.
[0028] Figure 2 To demonstrate that Avasimibe restores cholesterol metabolic homeostasis and improves cell membrane fluidity in an in vitro foam cell model, [the following diagram is provided].
[0029] Figure A shows MH-S cell lipidomics analysis; B shows quantitative analysis of cellular cholesterol and cholesterol esters; C shows the distribution of intracellular free cholesterol; and D shows changes in membrane fluidity.
[0030] Figure 3 To demonstrate that Avasimibe can improve lipophage disorder and slow down foam cell formation in an in vitro constructed foam cell model.
[0031] Figure A shows the detection and co-localization analysis of MH-S lipophage; B shows the KEGG analysis of lipidomics; and C shows the detection of intracellular lipid droplets.
[0032] Figure 4 To illustrate how Avasimibe reduces PHMG-induced abnormal extracellular matrix deposition.
[0033] Figure A shows the cell co-culture model; B and C show the detection of fibrosis-related markers in NIH3T3 cells after conditioned medium treatment; D shows the detection of TGF-β1 in the culture supernatant.
[0034] Figure 5To demonstrate the effectiveness of Avasimibe in vivo intervention in mice (Figure 1)
[0035] In the figure, A represents the intervention model; B represents changes in mouse body weight; C represents changes in mouse organ coefficients; D represents changes in mouse lung function; and E represents changes in SOAT1 levels in mouse lung tissue after intervention.
[0036] Figure 6 Figure showing the reduction in foam cell production and improvement in pulmonary fibrosis in mice after Avasimibe intervention.
[0037] In the figure, A and B represent changes in lipophage-related indicators; C represents Oil Red O staining of bronchoalveolar lavage fluid; D and E represent Western blotting of pulmonary fibrosis-related indicators; F represents HE staining and Masson staining of lung tissue; and G represents the detection of hydroxyproline in lung tissue. Detailed Implementation
[0038] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.
[0039] Example 1:
[0040] This example demonstrates an experiment on PHMG inhalation exposure leading to pulmonary fibrosis and lipid metabolism disorders in mice.
[0041] 1. Experimental materials:
[0042] 1.1 Wild-type male C57BL / 6J mice, 6-8 weeks old, were purchased from Beijing Vital River Company.
[0043] 1.2 HE staining kit, purchased from Wuhan Saiweier Biotechnology Co., Ltd.
[0044] 1.3 Masson staining kit, purchased from Wuhan Saiweier Biotechnology Co., Ltd.
[0045] 1.4 BODIPY 493 / 503 probes were purchased from Thermo Fisher Scientific, USA. Serum-free culture medium was used to prepare the working solution, and the solution was stored at -20°C protected from light.
[0048] 1.5 CD68 antibody was purchased from Shanghai Immunoway Co., Ltd., diluted 1:200 and stored at -20℃.
[0049] 1.6 SOAT1 antibody, purchased from Abcam, USA, was diluted 1:1000 and stored at -20°C.
[0050] 1.7% Polyhexamethylene guanidine hydrochloride, purchased from Shanghai Gaoju Biotechnology Co., Ltd., dissolved in ultrapure water to a concentration of 0.1%.
[0051] Inhalation via ultrasonic nebulization using a PHMG solution at a concentration of mg / mL.
[0052] 2. Experimental steps:
[0053] 2.1 Pathological staining of lung tissue: The obtained tissue was fixed in 4% paraformaldehyde and then dehydrated in ethanol at different concentration gradients. The tissue was then embedded in paraffin to prepare 0.5 μm thick tissue sections. These sections were stained with hematoxylin and eosin (HE), and collagen fibers were stained using the Masson trichrome method. Finally, the sections were observed under an optical microscope (EclipseCi-L, Nikon, Japan).
[0054] 2.2 Lipid Droplet Staining: Tissue sections were fixed for 60 min at room temperature using an immunostaining fixative. Cell membrane permeability was then achieved by treatment with Triton X-100 for 40 min, followed by incubation with blocking solution for 30 min. A diluted primary antibody solution was then added and incubated overnight at 4°C. The next day, fluorescent secondary antibody was added and incubated at 37°C for 2 h. The specificity of the fluorescent secondary antibody must match that of the primary antibody. Subsequently, lipid droplets (LDs) were stained with BODIPY 493 / 503 working solution for 30 min. Finally, cell nuclei were stained with DAPI. Images were captured using a Leica microscope.
[0055] 2.3 Lung Tissue Transcriptome Sequencing: Total RNA was isolated from lung tissue using TRIzol LS reagent, and a cDNA library was generated using the Oxford Nanopore Technology (ONT) cDNA-PCR Sequencing Kit (SQK-LSK 110+EXP-PCB 096). Template conversion activity of reverse transcriptase enhanced the generation of full-length cDNA, incorporating specific PCR adaptors into both ends of the first-strand cDNA. Then, 14 cycles of cDNA PCR were performed using the LongAmp Tag (NEB), followed by ligation of the resulting products with ONT adapters using T4 DNA ligase (NEB). DNA was purified using ONT technology and Agencourt XP beads. The final cDNA library was loaded into a FLO-MIN 109 flow cell at Biomarker Technologies (Beijing, China) and run on the PromethION platform. Differentially expressed genes (DEGs) were analyzed using Deseq 2 (1.34.0).
[0056] 2.4 SOAT1 Protein Immunoblotting Assay: First, lung tissue proteins were extracted, and protein quantification was performed using the BCA method. The upper and lower gel layers were prepared using a rapid PAGE gel preparation kit. Electrophoresis was performed at a constant voltage of 60V for 40 min, then adjusted to 120V and continued for another 60 min. Transfer buffer was prepared, and the PVDF membrane was activated with methanol and transferred at 280mA on ice for 2 h. After blocking with rapid blocking buffer for 1 h, SOAT1 primary antibody was added and incubated overnight at 4℃. The next day, the corresponding secondary antibody was added and incubated at room temperature for 2 h before development.
[0057] 3. Experimental Results:
[0058] Figure 1 A and Figure 1 B shows that PHMG inhalation exposure leads to pulmonary fibrosis in mice, accompanied by alveolar macrophage foaming.
[0059] Figure 1 C and Figure 1 D shows abnormal lipid metabolism in lung tissue, with upregulated steroid biosynthesis and cholesterol metabolism pathways, and upregulated SOAT1 expression.
[0060] Figure 1 E and Figure 1 F showed that the content of SOAT1 protein in the lung tissue of mice with pulmonary fibrosis was significantly increased.
[0061] Example 2:
[0062] This embodiment demonstrates that Avasimibe can restore cholesterol metabolic balance and improve cell membrane fluidity in an in vitro constructed foam cell model.
[0063] 1. Experimental materials:
[0064] 1.1 Mouse alveolar macrophages (MH-S) were purchased from Wuhan Pronosai Biotechnology Co., Ltd. MH-S cells were cultured in 1640 complete medium (90% 1640 basal medium + 10% fetal bovine serum + 1% penicillin-streptomycin antibiotics + 0.05mM β-mercaptoethanol) and in a constant temperature incubator at 37℃ and 5% CO2.
[0065] 1.2 Cholesterolase assay kit, purchased from Beijing Beyotime Biotechnology Co., Ltd.
[0066] 1.3 Filipin III staining kit, purchased from Targetmol, USA, dissolved in PBS and stored at -20°C.
[0067] 1.4 The Laurdan staining kit was purchased from Targetmol, USA. After dissolving in PBS, it was stored at -20°C.
[0068] 1.5 Avasimibe was purchased from InvivoChem in Guangzhou. It was dissolved in DMSO to prepare a stock solution, and then dissolved in culture medium to prepare a 4 μM working solution before use.
[0069] 2. Experimental steps:
[0070] 2.1 Construction of foam cell model: MH-S cells were exposed to PHMG (2.5 μg / ml) and ox-LDL (100 μg / ml) in combination to construct an in vitro foam cell model by providing exogenous lipids.
[0071] 2.2 Lipidomics assay of MH-S cells: After treatment, the precipitate of MH-S cells was collected, chloroform was added, and the cells were sonicated at 1620W on ice for 10 min, followed by sonication for 10 min and incubation overnight at 4°C. The cells were centrifuged at 12000 rpm at 4°C for 10 min, and 450 μL of the lower layer was evaporated to dryness. The cells were reconstituted with 200 μL of isopropanol-methanol (V:V = 1:1), vortexed for 30 s, sonicated in ice water for 3 min, and centrifuged again. The supernatant was analyzed using a liquid chromatography-mass spectrometry (LC-MS) system consisting of an ACQUITY UPLC I-Class plus ultra-high performance liquid chromatography-tandem high resolution mass spectrometer. Quality control samples (QCs) were prepared by mixing equal volumes of extracts from all samples, with each QC sample having the same volume as the original sample.
[0072] 2.3 Cholesterol Detection: After macrophage treatment, cell pellets were collected, and the levels of total cholesterol (TC) and free cholesterol (FC) were quantified using an enzyme assay kit (Applygen, Beijing, China). Cholesterol was measured at 550 nm using a microplate reader (Thermo Fisher Scientific, USA). Normalization was performed using a quinolinic acid (BCA) assay (Meilunbio, Dalian, China), and protein concentrations in cell lysates were measured and corrected using nitric acid. Macrophages treated with Filipin III probe staining were used to observe free cholesterol in the cells under a Leica microscope.
[0073] 2.4 Fluorescent probe staining: Cell slides were fixed with immunostaining fixative at room temperature for 60 min. Then, they were treated with Triton X-100 for 40 min to allow cell membrane permeability, followed by incubation with blocking solution for 30 min. Subsequently, fluorescent probe working solution was added for staining for 30 min. Images were captured using a Leica microscope.
[0074] 3. Experimental Results:
[0075] Figure 2 A shows that Avasimibe can improve changes in the lipid composition of cells in an in vitro foam cell model;
[0076] Figure 2 B and Figure 2 C showed that Avasimibe can improve the changes and distribution of cholesterol and cholesterol ester content in the foam cell model;
[0077] Figure 2 D shows that Avasimibe restores the fluidity of cell membrane structures.
[0078] Example 3:
[0079] This embodiment demonstrates that Avasimibe can improve lipophage disorder and slow down foam cell formation in an in vitro constructed foam cell model.
[0080] 1. Experimental materials:
[0081] 1.1LC3B antibody, purchased from Beijing Vibio Co., Ltd., was stored at -20℃.
[0082] 1.2 P62 antibody, purchased from Beijing Vibio Co., Ltd., stored at -20℃.
[0083] 2. Experimental steps:
[0084] 2.1. Staining for lipophage markers: Cell slides were fixed with an immunostaining fixative at room temperature for 60 min. Then, cell membrane permeability was achieved by treatment with Triton X-100 for 40 min, followed by incubation with blocking buffer for 30 min. A diluted primary antibody solution was then added and incubated overnight at 4°C. The next day, fluorescent secondary antibody was added and incubated at 37°C for 2 h. The specificity of the fluorescent secondary antibody must match that of the primary antibody. Finally, cell nuclei were stained with DAPI. Images were captured using a Leica microscope.
[0085] 2.2. Cell slides were fixed at room temperature for 60 min using an immunostaining fixative. Then, the slides were treated with Triton X-100 for 40 min to allow cell membrane permeability, followed by incubation with blocking solution for 30 min, and staining with BODIPY 493 / 503 working solution for lipid droplets (LDs) for 30 min. Finally, the cell nuclei were stained with DAPI. Images were captured using a Leica microscope.
[0086] 3. Experimental Results:
[0087] Figure 3 A shows that Avasimibe slowed the accumulation of LC3B and P62 and restored their fusion;
[0088] Figure 3 KEGG analysis using lipidomics showed that Avasimibe restored autophagy in cells;
[0089] Figure 3 C showed that Avasimibe slowed down the accumulation of lipid droplets.
[0090] This indicates that Avasimibe can restore the lipophagus function of cells and slow down the formation of foam cells.
[0091] Example 4:
[0092] This example demonstrates an experiment where Avasimibe reduced PHMG-induced abnormal extracellular matrix deposition in fibroblasts.
[0093] 1. Experimental materials:
[0094] 1.1 Mouse embryonic fibroblasts (NIH3T3 cells) were purchased from Wuhan Pronosei Biotechnology Co., Ltd.
[0095] 1.2 Fibronectin antibody, purchased from Abcam, USA, was diluted 1:1000 and stored at -20°C.
[0096] 1.3 Collagen I antibody, purchased from Abcam, USA, was diluted 1:1000 and stored at -20°C.
[0097] 1.4TGF-β1ELISA assay kit, purchased from Wuhan Boster Biological Technology Co., Ltd.
[0098] 2. Experimental steps:
[0099] 2.1 Cell Culture: NIH3T3 cells were cultured in high-glucose DMEM complete medium (90% high-glucose DMEM basal medium + 10% fetal bovine serum + 1% penicillin-streptomycin antibiotic) and in an incubator at 37°C and 5% CO2.
[0100] 2.2 Conditioned culture medium co-culture: MH-S cells were co-treated with PHMG and ox-LDL for 24 h, and then the supernatant of the culture medium was collected and used to treat NIH3T3 cells for 48 h.
[0101] 2.3 Detection of TGF-β1: The cell culture supernatant was centrifuged to remove the precipitate, and immediately analyzed or aliquoted, then frozen at -20℃. 100 μL of the diluted cell culture supernatant sample was added to each well of an ELISA plate, and the plate was sealed with a sealing film and incubated at 37℃ for 90 minutes. The plate was then discarded to remove any remaining liquid; washing was not required. Biotin-anti-mouse TGF-β1 antibody was added to each well at a volume of 100 μL of working solution. The plate was sealed again and incubated at 37℃ for 60 minutes. ABC working solution was added to each well at a volume of 100 μL of working solution. The plate was sealed again and incubated at 37℃ for 30 minutes. After washing with buffer, TMB chromogenic solution was added to each well at a volume of 90 μL of working solution and incubated at 37℃ in the dark for 25 minutes. Stop solution was added to each well at a volume of 100 μL of working solution, and the blue color was observed to change to yellow. The absorbance was measured at 450 nm using an ELISA reader.
[0102] 3. Experimental Results:
[0103] Figure 4 A is a diagram of a co-culture model using conditioned medium;
[0104] Figure 4 B and Figure 4 C shows that Avasimibe treatment of the culture supernatant reduced the induced transformation of fibroblasts;
[0105] Figure 4 D showed that the TGF-β1 content in the supernatant treated with Avasimibe was significantly reduced.
[0106] This indicates that Avasimibe can reduce abnormal deposition of the extracellular matrix.
[0107] Example 5:
[0108] This example is an in vivo intervention experiment of Avasimibe on mice.
[0109] 1. Experimental materials:
[0110] 1.1 Avasimibe was purchased from InvivoChem in Guangzhou. It was dissolved in DMSO to form a stock solution, and then dissolved in PBS before use.
[0111] 2. Experimental steps:
[0112] 2.1 Animal Intervention Experiment: Mice were randomly assigned to four different experimental groups, with 10 mice in each group. These were the saline group, the Avasimibe group, the PHMG group, and the PHMG+Avasimibe group. Avasimibe was purchased from Guangzhou.
[0113] Invivochem, for intraperitoneal administration. Avasimib was dissolved in dimethyl sulfoxide (DMSO), purchased from Solarbio Beijing. It was then diluted with physiological saline to achieve the desired concentration. Intraperitoneal injection of Avasimib was initiated one week after the mice's initial exposure to PHMG. Injections were given daily at fixed times at a dose of 15 mg / kg.
[0114] 2.2 Lung Function Testing in Mice: Mice were anesthetized with sodium pentobarbital, and lung function was measured using a fliiVent FX system (SCIREQ, Montreal, Canada). All tests were performed strictly in accordance with the manufacturer's guidelines and previous studies. The system was equipped with an FX1 module and an NPFE module, and data analysis was performed using fliiWare v7.2 software. Instrument parameters were set as follows: tidal volume 10 mL / kg, respiratory rate 150 breaths / min, inspiratory-to-expiratory ratio 2:3, and positive end-expiratory pressure 3 cmH2O. Forced expiratory volume in 0.05 seconds (FEV0.05), forced vital capacity (FVC), and other parameters were measured.
[0115] 3. Experimental Results:
[0116] Figure 5 A is a schematic diagram of the Avasimibe intervention experiment in mice;
[0117] Figure 5 B and 5C showed that the body weight and organ coefficient of the mice were improved to some extent after the intervention;
[0118] Figure 5 D shows that lung function was improved in mice after intervention;
[0119] Figure 5 E showed a decrease in SOAT1 expression after intervention;
[0120] The above demonstrates that Avasimibe's intervention is effective.
[0121] Example 6:
[0122] This example demonstrates an experiment showing reduced foam cell production and improved pulmonary fibrosis in mice after Avasimibe intervention.
[0123] 1. Experimental materials:
[0124] 1.1 Oil Red O staining kit, purchased from Beijing Solarbio Science & Technology Co., Ltd.
[0125] The 1,2-hydroxyproline detection kit was purchased from Hubei Pumei Technology Biotechnology Co., Ltd.
[0126] 2. Experimental steps:
[0127] 2.1 Acquisition of bronchoalveolar lavage fluid: Mice were first anesthetized with sodium pentobarbital at a dose of 10 mg / kg. After anesthesia, the mice were endotracheally intubated and injected with 1 ml of pre-cooled phosphate-buffered saline (PBS). 1.5 mL of PBS was slowly drawn into an EP tube using a syringe. This process was repeated three times to ensure complete collection of bronchoalveolar lavage fluid (BALF). The collected BALF was then centrifuged at 1000 g for 10 min to separate the cell pellet and supernatant, which were then frozen at -80°C for further analysis.
[0128] 2.2 Oil Red O staining: Cell smears were prepared from the bronchoalveolar lavage fluid sediment, fixed, rinsed with 60% isopropanol for 20 seconds, stained with Oil Red O reagent, and then mounted for observation under a microscope.
[0129] 2.3 Hydroxyproline determination: Mouse lung tissue was minced, digested in a water bath, and the supernatant was collected. The pH was then adjusted and the volume was brought to a constant. The absorbance was measured using a reagent kit and calculated.
[0130] 3. Experimental Results:
[0131] Figure 6 A and Figure 6 B shows that Avasimibe restored lipophage function in mouse lung tissue;
[0132] Figure 6 C showed a significant reduction in foam cells in the bronchoalveolar lavage fluid after the intervention;
[0133] Figure 6 D and Figure 6 E showed that Avasimibe intervention significantly downregulated pulmonary fibrosis-related markers in mice;
[0134] Figure 6 F showed that the intervention reduced pathological changes and collagen deposition in lung tissue;
[0135] Figure 6 G showed that Avasimibe intervention significantly reduced HYP levels.
[0136] The above demonstrates that Avasimibe intervention can play a certain therapeutic role in PHMG inhalation-induced pulmonary fibrosis.
Claims
1. Application of Avasimibe in the preparation of drugs for treating pulmonary fibrosis.
2. The application as described in claim 1, characterized in that: Avasimibe reduces the production of foam cells by targeting SOAT1, thereby alleviating the development and progression of pulmonary fibrosis.
3. The application as described in claim 1, characterized in that: Avasimibe alleviates the development of pulmonary fibrosis by restoring the homeostasis of cholesterol and cholesterol esters.
4. The application as described in claim 1, characterized in that: Avasimibe alleviates the development of pulmonary fibrosis by improving the fluidity of cell membrane structures.
5. The application as described in claim 1, characterized in that: Avasimibe alleviates the development and progression of pulmonary fibrosis by restoring lipophage function.