Application of ZLN005 in the preparation of drugs for treating silicosis

Abstract

The present invention discloses the application of ZLN005 in the preparation of a medicament for treating silicosis, which relates to the technical field of biomedicine. In the present invention, ZLN005 treatment is administered to silica-stimulated rat macrophages and a mouse silicosis model to explore its effects on lipid metabolism disorders and pulmonary fibrosis in silicosis. The results show that silica induces lipid metabolism disorders in NR8383 macrophages, and ZLN005 alleviates the lipid metabolism disorders in macrophages and silicosis mice and inhibits pulmonary fibrosis. Therefore, ZLN005 shows an anti-fibrotic effect by reducing lipid metabolism disorders in silicosis mice. The present invention provides substantial evidence for the efficacy of ZLN005 in silicosis fibrosis. ZLN005 improves lipid metabolism disorders and inhibits SiO2-induced fibrosis, indicating that ZLN005 can treat silicosis and inhibit silicosis fibrosis.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technologies, and particularly to the use of ZLN005 in the preparation of a medicament for treating silicosis. Background Art

[0002] Silicosis is a potential interstitial lung disease caused by long-term inhalation of a large amount of free silica dust, characterized by persistent inflammation and permanent pulmonary fibrosis. The abundance of silica in the earth's crust and its presence in a very wide range of industrial environments result in a high incidence of silicosis. At present, the clinical treatment methods for this disease are limited. Lung lavage, lung transplantation, and stem cell therapy are all restricted by short-term treatment effects and frequent adverse effects. Due to the complex pathogenesis of silicosis, the existing prevention and treatment means still cannot effectively improve silicosis damage. Therefore, it is urgent to deeply clarify the pathogenesis of silicosis, explore new intervention targets and prevention and treatment means, which has very important practical significance and clinical application value. Summary of the Invention

[0003] The object of the present invention is to provide the use of ZLN005 in the preparation of a medicament for treating silicosis, so as to solve the problems existing in the above-mentioned prior art. The present invention has found through research that ZLN005 can inhibit silicosis fibrosis, and thus can be used in the preparation of a medicament for treating silicosis.

[0004] In the lungs, macrophages constitute the first line of defense against pathogens and foreign substances and play an important role in maintaining tissue homeostasis. Previous studies have confirmed that after macrophages phagocytose silica entering the alveoli, they release inflammatory factors, amplifying the inflammatory response in the lungs. In addition, macrophages can stimulate the proliferation and migration of fibroblasts by secreting transforming growth factor-β1, accelerating the progression of pulmonary fibrosis. Newly discovered research shows that silica can cause lipid metabolism disorders in macrophages, exacerbate the accumulation of lipids in macrophages, and induce the formation of foam cells. In addition, studies have confirmed that the oxidized low-density lipoprotein (ox-LDL) in the bronchoalveolar lavage fluid of silicosis patients is reduced, while the ox-LDL in the macrophages of the bronchoalveolar lavage fluid is increased. The intake of ox-LDL is the key to macrophage foamification, exacerbating the accumulation of lipids in cells. As is well known, lipid metabolism is a special metabolic mode of the lungs, mainly obtaining energy through fatty acid oxidation under hypoxic conditions, and lipids such as phospholipids and sphingolipids are important components in the synthesis of pulmonary surfactant, playing an important role in maintaining normal alveolar surface tension. Previous research of the present invention has found that silica promotes lipid metabolism disorders in macrophages and may trigger the production of profibrotic factors, accelerating the progression of silicosis. These studies indicate that lipid metabolism disorders play an important role in the progression of silicosis fibrosis.

[0005] Peroxisome proliferator-activated receptor-γ coactivator-1α is a key factor in lipid and metabolism regulation and plays a crucial role in maintaining lipid homeostasis. It has been reported that PGC1α can improve diabetic kidney injury by regulating the LXR-ABCA1 signaling pathway to mediate renal cholesterol efflux. In addition, PGC1α can also improve renal interstitial fibrosis by regulating CD36-mediated lipid metabolism disorders. Our previous studies have confirmed that CD36 is involved in regulating lipid metabolism disorders in silicosis, indicating that PGC1α is a key gene regulating lipid metabolism disorders and may play an important role in silicosis lipid metabolism. However, so far, the mechanism of PGC1α in the progression of silicosis remains unclear. This invention explores the protective effect of ZLN005 in promoting lipid homeostasis and its possible regulatory mechanism on silicosis fibrosis.

[0006] Based on this, the present invention provides the following solutions:

[0007] The present invention provides the use of ZLN005 in the preparation of a drug for treating silicosis.

[0008] Further, the treatment of silicosis refers to inhibiting the fibrosis of silicosis.

[0009] Further, the silicosis is induced by silica.

[0010] The present invention also provides a drug for treating silicosis, comprising ZLN005.

[0011] Further, the drug further comprises a pharmaceutically acceptable excipient.

[0012] Further, the dosage form of the drug includes tablets, granules, capsules, powders or injections.

[0013] The present invention also provides the use of ZLN005 in the preparation of a drug for improving lipid metabolism disorders.

[0014] Further, the lipid metabolism disorders are induced by silica.

[0015] The present invention discloses the following technical effects:

[0016] ZLN005 is an activator of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). In order to explore whether ZLN005 can slow down the progression of silicosis fibrosis, the present invention administered ZLN005 treatment in rat macrophages and mouse silicosis models stimulated by silica to explore its effects on silicosis lipid metabolism disorders and pulmonary fibrosis. The results showed that silica induced lipid metabolism disorders in NR8383 macrophages, and ZLN005 slowed down lipid metabolism disorders in macrophages and silicosis mice, and inhibited pulmonary fibrosis. Therefore, ZLN005 showed anti-fibrotic effects by reducing lipid metabolism disorders in silicosis mice. The present invention provides substantial evidence for the efficacy of ZLN005 in silicosis fibrosis. ZLN005 improved lipid metabolism disorders and inhibited SiO 2 This suggests that ZLN005 can treat silicosis and inhibit silicotic fibrosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0018] Figure 1 Oil red O staining and western blot detection of SiO 2 The results of the effects on lipids in NR8383 cells; A is the result of Oil Red O staining; B is the western blot detection result of PGC1α; CE are the statistical results of the relative contents of PGC1α, CD36 and LXR respectively;

[0019] Figure 2 ZLN005 to SiO 2 The effects of induced lipid metabolism disorder; A is the western blot detection result of PGC1α under different ZLN005 concentrations; B is the statistical result of the relative content of PGC1α; C is the cell survival rate; D and E are the results of immunofluorescence staining and BODIPY staining, respectively; FH are the contents of FC, TC and CE, respectively; I is the ratio of CE; J is the result of Western blot detection of the expression of lipid-related factors CD36, PGC1α, LXR and ABCA1 in cells; KN is the statistical result of the relative content of CD36, ABCA1, LXR and PGC1α; the scale bars in D and E are 20μm;

[0020] Figure 3Two-dimensional ion intensity map of retention time and mass-to-charge ratio for the ZLN005-stimulated SiO2-induced macrophage samples;

[0021] Figure 4 For the positive ion PCA score plot (A), OPLS-DA plot (B), S-plot (C) and permutation score plot (D) of ZLN005-stimulated SiO 2 induced macrophages;

[0022] Figure 5 For the negative ion PCA score plot (A), OPLS-DA plot (B), S-plot (C) and permutation score plot (D) of ZLN005-stimulated SiO 2 induced macrophages;

[0023] Figure 6 For the differential metabolites of positive ions in ZLN005-stimulated SiO 2 induced macrophages;

[0024] Figure 7 For the differential metabolites of negative ions in ZLN005-stimulated SiO 2 induced macrophages;

[0025] Figure 8 For the enrichment analysis of differential metabolites in ZLN005-stimulated SiO 2 induced macrophages;

[0026] Figure 9 For the pathway analysis of differential metabolites in ZLN005-stimulated SiO 2 induced macrophages;

[0027] Figure 10 For the effect of ox-LDL on the expression of lipid-related factors in NR8383 cells; among them, A is the result of Oil Red O staining; B is the result of western blot detection of lipid-related factors; C-E are the statistical results of the relative contents of lipid-related factors PGC1α, CD36 and LXR respectively;

[0028] Figure 11 For the BODIPY staining result of using ZLN005 to activate PGC1 expression;

[0029] Figure 12Effects of ZLN005 on lipid metabolism disorder and fibrosis in silicosis mice; among them, A shows the results of HE and VG staining; B shows the results of BODIPY staining, Oil Red O staining, CD36 immunofluorescence and PGC1α immunofluorescence staining respectively; C-E show the contents of TC, FC and CE respectively; F shows the proportion of CE; G shows the results of detecting the expression of PGC1α, LXR, CD36, Eca, COLI and IL-6 by Western blot; H-M show the statistical results of the relative contents of PGC1α, LXR, CD36, Eca, COLI and IL-6. Detailed implementation manners

[0030] Now, various exemplary implementation manners of the present invention will be described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and implementation schemes of the present invention.

[0031] It should be understood that the terms used in the present invention are only for describing particular implementation manners and are not used to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the range.

[0032] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0033] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific implementation manners of the present invention specification, which are obvious to those skilled in the art. Other implementation manners obtained from the present invention specification are also obvious to those skilled in the art. The present invention specification and examples are only exemplary.

[0034] Regarding "comprising", "including", "having", "containing", etc. used herein, they are all open-ended terms, meaning including but not limited to.

[0035] Term description: ZLN005 referred to in the present invention has a CAS number of 49671-76-3, and its structural formula is as follows:

[0036] Example 1

[0037] 1. Materials and methods

[0038] 1.1 Animals and sample collection

[0039] Male C57BL / 6J mice at 8 weeks of age were purchased from Beijing Huafukang Biotechnology Co., Ltd. [License number: SCXK (Beijing) 2019-0008] and were housed in the Animal Experiment Center of North China University of Science and Technology [License number: SYXK (Hebei) 2020-007]. All mice were kept in a specific pathogen-free facility and maintained under conditions of constant temperature (23-25 °C), humidity (40-50%), and a 12-hour light / dark cycle. All experiments involving mice were approved by the Animal Experiment Ethics Committee of North China University of Science and Technology (Ethical approval number: SK2022128) and complied with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, USA.

[0040] The mice were randomly divided into 3 groups (n = 6 per group) as follows: (1): control group (C), (2) silica group (SiO 2 ), (3) silica plus ZLN005 group (SiO 2 +ZLN005). The control group was perfused with 50 μL of normal saline; the SiO 2 and SiO 2 +ZLN005 groups were instilled with 50 μL of silica suspension (5 mg / mouse, s5631, Sigma-Aldrich, St. Louis, MO, USA) into the trachea to induce silicosis. One week after the mice were exposed to silica, the mice in the SiO 2 +ZLN005 group were intraperitoneally injected with 12 mg / kg of ZLN005 (14121, Cayman, Cayman Chemical Company, USA) daily for 4 weeks, and then the lungs were harvested and stored at -80 °C.

[0041] 1.2 Histopathological observation of lung tissue

[0042] The lung tissues of rats were fixed with 4% paraformaldehyde solution and embedded in paraffin. Paraffin sections were prepared, and HE staining was performed to observe histopathological changes, while VG staining was used to detect fibrosis. The lung tissues of rats were fixed with 4% paraformaldehyde solution, dehydrated with 30% sucrose, embedded in OCT, and frozen sections were prepared. Oil red O staining and BODIPY staining were used to observe lipid levels. Pathological images were observed using an Olympus DP80 optical microscope (Olympus Corporation, Tokyo, Japan). After cell fixation, BODIPY staining was performed to observe intracellular lipid droplets. Observation was carried out using an Olympus FLUOVIEW FV-1000 laser scanning confocal microscope (Olympus Corporation, Tokyo, Japan).

[0043] 1.3 Immunofluorescence staining (IF)

[0044] For IF staining, paraffin sections of lung tissues and cell smears were incubated overnight at 4°C with antibodies against CD36 (Huaan Biotechnology Company, China), COLΙ (Affinity Biosciences, UK), IL-6 (Huaan Biotechnology Company, China), and PGC1α (Santa Cruz Biotechnology, USA). Incubation with the secondary antibody was carried out at 37°C for 60 min. The cell nuclei were stained with DAPI (8961s; Cell Signaling Technology, Inc., Danvers, MA, USA).

[0045] 1.4 Lipidomics

[0046] Methanol-acetonitrile (1:1) extraction solution was added to the cells, and then ultrasonic treatment was performed. The mixture was placed at -20°C for 4 h, centrifuged at 12,000 rpm for 20 min at 4°C, and the supernatant was taken. Subsequently, it was centrifuged at 12,000 rpm for 5 min at 4°C, and the supernatant was taken again.

[0047] Lipid analysis was performed using a combination of Waters I-Class Acquity UPLC (Waters, Elstree, UK) and Vion IMS QToF (Waters, Elstree, UK), with a BEH C18 1.7 μm chromatographic column (2.1 × 100 mm i.d.) (Waters, Inc., Elstree, UK). The fragment ion spectra were analyzed in MSE mode. Mobile phase A consisted of 0.1% formic acid, and mobile phase B consisted of acidic acetonitrile and methanol (1:1, v / v) with 0.1% formic acid. The fragment ion mass spectrometry analysis was performed in MSE mode. Lipid metabolites were separated by gradient elution under the following conditions. 0 - 1 minute, 99% - 70% A; 2.5 - 6.5 min, 40% - 10% A; 7 - 10 minutes, 0% A; the column temperature was maintained at 45 °C. The flow rate was 0.4 mL / min. The parameters are shown below. MS range, m / z 50 - 1000; scan time 0.2 s; cone voltage, 60 V; desorption temperature 500 °C; source temperature, 120 °C; desorption gas, 1000 l / h; cone gas, 50 l / h; capillary voltage, 2000 V. Locked calibration (locked nebulizer reference: mass, 556.2766 m / z; sampling time, 0.5 minute; CE, 60 V; flow rate 10 μL / min). To eliminate instrumental errors, quality control (QC) samples were prepared by mixing all lung tissue or cell samples. The QC samples were inserted into the detection queue to monitor and evaluate the stability and reliability of the system during the experiment.

[0048] Peak identification, peak extraction, and deconvolution calculations were performed on the original LC / MS data using Progenesis QI, and principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed using Ezinfo. Lipids were identified by combining the Human Metabolome Database (HMDB) (https: / / hmdb.ca / ), KEGG, Mass Bank, and LipidMaps (http: / / lipidmaps.org) and Lipidblast, and finally, the metabolic pathways most relevant to lipid differential metabolites were identified using Metaboanalyst 5.0 (https: / / www.metaboanalyst.ca / ).

[0049] 1.5 Cell culture and treatment

[0050] Rat alveolar macrophage NR8383 cells were purchased from the Shanghai Institute of Cell Biology, Chinese Academy of Sciences. The cells were cultured in F12K medium with 15% fetal bovine serum by volume fraction. First, the stimulation concentration of ZLN005 was screened based on the expression of PGC1α and cell viability. In addition, SiO with a concentration of 50 μg / mL 2NR8383 macrophages were treated with ox-LDL at 50 μg / mL for 36 h. In SiO 2 and at 12 h after ox-LDL stimulation, ZLN005 (20 μM) was added to the culture medium, and then the cells were incubated for 24 h. The experimental groups were set as control group (C), ZLN005 group, SiO 2 group, and ZLN005 + SiO 2 group. Among them, group C: cultured normally in normal medium; ZLN005 group: stimulated with ZLN005 at a final concentration of 20 μM for 24 h; SiO 2 group: stimulated with SiO 2 at a final concentration of 50 μg / mL for 36 h; ZLN005 + SiO 2 group: stimulated with SiO 2 at a final concentration of 50 μg / mL for 36 h, and at the 12th h, treated with ZLN005 at a final concentration of 20 μM for 24 h.

[0051] 1.6 Western blot

[0052] The Western blot detection was performed using the method described in "Hao X, Jin Y, Zhang Y, et al. Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K / AKT Pathway[J]. Int J Mol Sci, 2023, 24(1): 774". The primary antibodies used in the detection included β-Actin (Boster Biotechnology, China), COLΙ (Affinity Biosciences, UK), PGC1α (Santa Cruz Biotechnology, USA), LXR (HuaAn Biotechnology, China), ABCA1 (HuaAn Biotechnology, China), CD36 (HuaAn Biotechnology, China). After incubating with the primary antibody, the lung tissue and cell samples were incubated with goat anti-rabbit or anti-mouse secondary antibody at a concentration of 1:5000 for 2 hours. The target bands were detected using ECL developing solution.

[0053] 1.7 Measurement of total cholesterol, free cholesterol and cholesterol esters in cells

[0054] According to the kit instructions, the microplate reader measures the levels of total cholesterol (TC) and free cholesterol (FC) at 500 nm, and calculates the content of intracellular cholesterol ester (CE) and the proportion of CE. CE% = (TC - FC) / TC.

[0055] 1.8 Statistical analysis

[0056] Statistical analysis was performed using SPSS 21 software. All results were expressed as mean ± SD and were obtained from at least 3 experiments. One-way analysis of variance (ANOVA) was used to compare the means of more than two groups, followed by LSD test. Independent-samples t-test was used to compare the means of two groups of samples. P < 0.05 was considered statistically significant.

[0057] 2. Results

[0058] 2.1 SiO 2 Induces lipid metabolism disorder in macrophages

[0059] In the present invention, Oil Red O staining and western blot were used to detect the effect of SiO 2 on lipids in NR8383 cells. The results of Oil Red O staining found that lipid increased after SiO 2 stimulation ( Figure 1 in A). Western blot showed that PGC1α and LXR were significantly down-regulated in the SiO 2 stimulation group, and CD36 was significantly up-regulated in the SiO 2 stimulation group ( Figure 1 in B - C). The above suggests that SiO 2 induces lipid metabolism disorder in macrophages.

[0060] 2.2 ZLN005 alleviates the lipid metabolism disorder induced by SiO 2 Induced lipid metabolism disorder

[0061] To explore the effect of ZLN005 on the lipid metabolism disorder induced by SiO 2 First, the concentration of ZLN005 stimulating cells was screened, and the expression of PGC1α was detected by western blot. The results found that the expression of PGC1α was the highest under the condition of 20 μM, and the cell viability was not inhibited ( Figure 2 in A - C). The results of immunofluorescence staining and BODIPY staining ( Figure 2 in D and E) found that compared with group C, the expression of PGC1α decreased and the lipid content increased after SiO 2 stimulation. After ZLN005 stimulation, compared with the SiO 2 group, the expression of PGC1α increased and the lipid content decreased. In addition, ZLN005 also inhibited SiO 2Induced elevation of TC, FC, and CE ( Figure 2 in F-I). Western blot was used to detect the expression of lipid-related factors in cells. Compared with group C, after SiO 2 stimulation, the expression of PGC1α, LXR, and ABCA1 decreased, while the expression of CD36 increased. After overexpressing ZLN005, the decrease in PGC1α, LXR, and ABCA1 and the increase in CD36 caused by SiO 2 stimulation were inhibited ( Figure 2 in J-N). This suggests that ZLN005 alleviated the lipid metabolism disorder induced by SiO 2 .

[0062] 2.3 ZLN005 regulates lipid metabolites in SiO 2 induced lipid metabolism disorder

[0063] To further explore the changes in lipid metabolites or metabolic pathways involved in ZLN005 in improving SiO 2 induced lipid metabolism, lipid metabolomics analysis was performed on NR8383 cells in the SiO 2 group and the ZLN005 + SiO 2 group. The positive and negative ion intensity maps of the two groups had similar ion distributions ( Figure 3 ), indicating that the metabolomic characteristics of the two groups were comparable. The PCA results ( Figure 4 in A and Figure 5 in A) showed that the SiO 2 group and the ZLN005 + SiO 2 group had clear sample clusters (positive ions: R2X = 0.434, Q2 = 0.187, negative ions: R2X = 0.307, Q2 = 0.181), indicating differences in metabolites between different groups. To further analyze the metabolic differences between the two groups, OPLS-DA and S-plot analysis were applied ( Figure 4 in B-C, Figure 5 in B-C), and the results showed that the SiO 2 group and the ZLN005 + SiO 2 group were clearly separated (positive ions: R2Y = 0.993, Q2 = 0.937, negative ions: R2Y = 0.989, Q2 = 0.886). The 200-iteration cross-validation test ( Figure 4 in D and Figure 5 in D) showed that the model did not overfit, indicating that all models were reliable. In addition, compared with the SiO 2 group, 71 lipid metabolism biomarkers were obtained in the ZLN005 + SiO 2 group, among which 51 differential lipid metabolites were up-regulated and 20 differential lipid metabolites were down-regulated ( Figures 6 - 7)。Based on the MetaboAnalyst 5.0 software, the metabolic pathways of these differential metabolites were analyzed. In the present invention, Impact > 0.1 was used as the screening condition for the most important metabolic pathways, and it was found that the differential metabolites were mainly enriched in glycerophospholipid metabolism, linolenic acid metabolism, glutathione metabolism, and glycerolipid metabolism( Figures 8 - 9 )。

[0064] 2.4 ox-LDL induces macrophage lipid metabolism disorder

[0065] To determine the effect of ox-LDL on the expression of lipid-related factors in NR8383 cells, the present invention used ox-LDL to stimulate NR8383 cells. The results of Oil Red O staining showed an increase in lipids after ox-LDL stimulation( Figure 10 in A). Western blot showed that PGC1α and LXR were significantly down-regulated in the ox-LDL stimulation group, and CD36 was significantly up-regulated in the ox-LDL stimulation group( Figure 10 in B-E). These results indicate that ox-LDL plays a key role in macrophage lipid metabolism.

[0066] 2.5 ZLN005 alleviates ox-LDL-induced macrophage lipid metabolism disorder

[0067] Next, the present invention used ZLN005 to activate the expression of PGC1α. The results of BODIPY staining( Figure 11 ) found that compared with Control, the lipid content increased after ox-LDL stimulation. After ZLN005 stimulation, compared with the ox-LDL group, the lipid content decreased. It is suggested that ZLN005 alleviates ox-LDL-induced lipid metabolism disorder.

[0068] 2.6 ZLN005 alleviates lipid metabolism disorder and fibrosis in silicosis mice

[0069] Since it was observed that ZLN005 inhibited lipid metabolism disorder in macrophages, the present invention considered whether ZLN005 could alleviate the fibrotic response to silica in vivo. To verify this hypothesis, the present invention administered ZLN005 treatment to mice exposed to silica. ZLN005 attenuated fibrosis in silicosis mice. And Oil Red O staining and BODIPY staining( Figure 12 in A-B) found that the lipids in the lung tissue of silicosis mice increased. After ZLN005 treatment, the lipid disorder was improved. Immunofluorescence and western blot observed that the expression of PGC1α decreased and the expression of CD36 increased in the lung tissue of silicosis mice. ZLN005 reversed the expression of PGC1α and CD36 in silicosis mice( Figure 12 in G-M). In addition, ZLN005 also inhibited the increase in TC, FC, and CE in the serum of silicosisFigure 12 In (C-F). In summary, these data support the anti-fibrotic effect of ZLN005 by inhibiting lipid metabolic disorders in macrophages.

[0070] The above-described embodiments are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. Use of ZLN005 in the preparation of a medicament for treating silicosis, Characterized in that, the CAS number of the said ZLN005 is 49671-76-3, and the structural formula is as follows: 。

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