阿拉伯木聚糖在制备治疗肺纤维化药物中的应用

Abstract

本发明公开了一种阿拉伯木聚糖制备治疗肺纤维化药物中的应用，属于药品技术领域。本申请的发明人经过大量的研究发现，阿拉伯木聚糖（Arabinoxylan，AX）具有非常明显的肺纤维化治疗作用：不仅可以抑制博莱霉素（bleomycin，BLM）致实验小鼠肺纤维化的病理学表现及肺中羟脯氨酸含量，提高BLM诱导的肺纤维化小鼠的存活率和体重，降低博莱霉素处理实验小鼠的肺湿重 / 体重比值；减少BLM致实验小鼠纤维化肺中I型胶原蛋白（collagen）和肌成纤维细胞标志物平滑肌动蛋白（α‑Sma）的表达；减少BLM致实验小鼠纤维化肺中S100a8 mRNA和蛋白水平的表达；且AX降低TGF‑β1诱导的人肺成纤维细胞的增殖；改善在实验小鼠肺纤维化模型中由BLM导致的肺上皮细胞的缺失；还能够减少上皮细胞浸润从而减少炎症，从而在很大程度上可以抑制肺纤维化。因此，阿拉伯木聚糖可以用于制备治疗肺纤维化的药物。

Description

Technical Field

[0001] This invention relates to the fields of clinical medicine and biopharmaceutical technology, and more specifically to the application of arabinoxylan in the preparation of drugs for treating pulmonary fibrosis. Background Technology

[0002] Pulmonary fibrosis is the final pathological change in many interstitial lung diseases. It is characterized by damage and death of lung epithelial cells leading to long-term diffuse alveolitis, which in turn causes excessive proliferation of fibroblasts, differentiating them into myofibroblasts that highly express Collagen and α-Sma. This results in excessive deposition of extracellular matrix, primarily composed of Collagen, which gradually replaces normal lung tissue, ultimately causing pulmonary dysfunction and death from respiratory failure. Studies suggest that various factors, including pathogens, dust, drugs, and chemical agents, can induce pulmonary fibrosis, but the detailed mechanisms remain unclear. It has been reported that some proteins play important roles in the process of pulmonary fibrosis. For example, elevated levels of S100A8 in the serum of IPF patients can promote the proliferation and differentiation of lung fibroblasts and the progression of BLM-induced pulmonary fibrosis in mouse models. S100A8 is also considered an effective therapeutic target for IPF and a promising prognostic biomarker for IPF.

[0003] Currently, there are no treatment strategies or drugs that can cure pulmonary fibrosis or reverse existing pulmonary fibrosis. For example, only two FDA-approved drugs for PF treatment, pirfenidone (PFD) and nintedanib, are ineffective in PF patients with severe lung function decline and have significant side effects. Other drugs used clinically for pulmonary fibrosis include glucocorticoids, interferon-gamma (IFN-γ), cytotoxic drugs (azathioprine, cyclophosphamide, etc.), and antioxidants (N-acetylcysteine, etc.). Among these, glucocorticoids are currently the main clinical choice, but these drugs have significant side effects, severely affecting the body's immune function and increasing the possibility of secondary infections; interferon-gamma has many adverse reactions and is prone to inducing tolerance; cytotoxic drugs have poor selectivity, many adverse reactions, and their efficacy is not ideal. In addition, metformin has been reported to inhibit BLM-induced pulmonary fibrosis in mice, but metformin has been reported to enhance nephrotoxicity. Therefore, it is necessary to develop new, highly effective, and safe drugs for the treatment of pulmonary fibrosis.

[0004] Arabicinoxylan (AX), found in the cell walls of all major cereal plants, is a safe and non-toxic cereal polysaccharide fiber. In 2018, it was approved by the US FDA as a dietary fiber, allowing its addition to foods or dietary supplements. AX has been reported to have the potential to alter lipid metabolism and redox homeostasis in humans and animals. Studies have shown that arabinoxylan, as an effective antioxidant, protects the hematopoietic system in mice by preventing free radical formation, regulating lipid peroxidation, enhancing the antioxidant defense system, and preventing oxidative stress. Furthermore, based on its various biological activities, arabinoxylan also exhibits anti-diabetic and anti-cancer effects. The anti-pulmonary fibrosis effects of natural products have attracted significant attention from scientists and have gradually become a research hotspot in recent years. Therefore, whether and how arabinoxylan can be applied to the preparation of drugs for treating pulmonary fibrosis is a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, the present invention applies arabinoxylan to the preparation of drugs for treating pulmonary fibrosis, providing a clinical basis for the treatment of pulmonary fibrosis.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] Arabica xylan can alleviate pulmonary fibrosis, thus it can be used in the preparation of drugs for the treatment of pulmonary fibrosis.

[0008] As a preferred technical solution of the present invention, arabinoxylan can significantly reduce the collagen deposition fraction, pulmonary fibrosis fraction, tracheal deposition thickness and hydroxyproline content in the lungs of mice with BLM-induced pulmonary fibrosis, improve the survival rate and body weight of mice with BLM-induced pulmonary fibrosis, and reduce the ratio of lung wet weight to body weight in mice with BLM-induced pulmonary fibrosis.

[0009] As a preferred technical solution of the present invention, arabinoxylan can downregulate the expression levels of collagen I and α-Sma in the lung tissue of BLM-induced pulmonary fibrosis in mice.

[0010] As a preferred technical solution of the present invention, arabinoxylan can downregulate the expression level of S100a8 in the lung tissue of BLM-induced pulmonary fibrosis in mice.

[0011] As a preferred technical solution of the present invention, arabinoxylan can downregulate the proliferation level of TGF-β1-induced human lung fibroblasts.

[0012] As a preferred technical solution of the present invention, arabinoxylan can improve the loss of airway epithelial cells in the fibrotic lung tissue of mice after BLM induction.

[0013] As a preferred technical solution of the present invention, arabinoxylan can downregulate the infiltration of inflammatory cells in the fibrotic lung tissue of mice after BLM-induced fibrosis.

[0014] One drug used to treat pulmonary fibrosis includes arabinoxylan.

[0015] As a preferred technical solution of the present invention, the concentration of arabinoxylan used is 200 mg / kg (in vivo mouse experiment) and 10 μg / ml (in vitro cell experiment).

[0016] As can be seen from the above technical solution, compared with the prior art, the present invention applies arabinoxylan to the preparation of drugs for treating pulmonary fibrosis with significant effects, providing a theoretical and clinical basis for the treatment of pulmonary fibrosis. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0018] Figure 1 The attached figure shows the results of arabinoxylan inhibition of BLM-induced pulmonary fibrosis in mice provided by this invention. A represents a Masson-stained lung section (collagen stained blue) on day 21 after modeling in bleomycin-induced pulmonary fibrosis model mice treated with AX (scale bar: 100 μM); PFD (pirfenidone) and MTF (metformin) serve as drug controls with therapeutic effects. BD shows the quantitative results of three pulmonary fibrosis-related parameters—Ashcroft score (B), collagen volume fraction (C), tracheal wall thickness (D), and hydroxyproline analysis (E)—on Masson-stained lung sections. FH shows the survival rate (F), body weight (G), and lung wet weight / body weight (H) of control PBS mice, BLM-treated mice, BLM-treated mice treated with AX, and AX-treated mice from day 1 to 21 after modeling. n=6 / group ( Figure 1 AE, and G, H), or n=19-23 / group ( Figure 1 F). * P <0.05,** P <0.01, *** P <0.001, **** P <0.0001;

[0019] Figure 2The attached figures show the downregulation of collagen I and α-Sma protein levels in lung tissue of BLM-induced pulmonary fibrosis mice by arabinoxylan (scale bar: 100 μM). A and B: Representative images of lung sections from AX-treated BLM-PF model mice harvested on day 21 post-modeling, showing immunofluorescence staining of collagen (A) and quantification results of the collagen / DAPI fluorescence ratio using ImageJ software (B). C and D: Representative images of lung sections from AX-treated BLM-PF model mice harvested on day 21 post-modeling, showing immunofluorescence staining of α-Sma (C) and quantification results of the α-Sma / DAPI fluorescence ratio using ImageJ software (D). n=3 / group. * P <0.05,** P <0.01, **** P <0.0001;

[0020] Figure 3 The attached figure shows that arabinoxylan can downregulate the protein and mRNA expression levels of S100a8 in lung tissue of BLM-induced pulmonary fibrosis mice. A and B, AX-treated BLM-PF model mice, lung sections harvested on day 21 post-modeling, show representative images of S100a8 immunofluorescence staining (A) and the expression levels of S100a8 in the lungs. S100a8 Transcript levels (B, n=3 / group). Scale bar is 50 μm. * P <0.05;

[0021] Figure 4 The attached figure shows that arabinoxylan downregulates TGF-β1-induced proliferation in human lung fibroblasts, but does not alter the proliferation of normal human lung fibroblasts. A and B: Human primary lung fibroblasts were treated with TGF-β1 and AX (A), or with different concentrations of AX (B), for 24 hours, and cell viability was detected using the MTT assay. The experiment was repeated three times. * P <0.05;

[0022] Figure 5 The attached figure shows how arabinoxylan can improve the loss of airway epithelial cells (Ccsp as a marker of airway epithelial cells) in the fibrotic lung tissue of mice after BLM-induced fibrosis (scale bar: 100 μM). A and B, representative images of lung sections harvested on day 21 after modeling in AX-treated BLM-PF mice, show double immunofluorescence staining for α-Sma and Ccsp (A, white triangles indicate bronchioles), and the quantitative results of the relative area of ​​Ccsp / α-Sma fluorescence signal around the trachea using ImageJ (B). n=3 / group. * P <0.05,** P <0.01, **** P <0.0001;

[0023] Figure 6 The attached figure shows that arabinoxylan can downregulate macrophages (F4 / 80) in lung tissue of mice with pulmonary fibrosis after BLM-induced pulmonary fibrosis. + ) and T lymphocytes (Cd3) + ) infiltration (scale bar: 50 μM). Detailed Implementation

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] In the examples, arabinoxylan is represented by AX;

[0026] Example 1: Construction of a mouse pulmonary fibrosis model: C57BL / 6J mice (8-13 weeks old, 22-25g in weight) were randomly divided into two groups. The bleomycin (BLM) treatment group was intratracheally instilled with 0.05mL of BLM at a dose of 1.5 units / kg, while the control group was instilled with the same volume of PBS.

[0027] Tracheal drip irrigation steps

[0028] (1) Disinfect tools such as tweezers used for modeling in advance;

[0029] (2) Mice were anesthetized by intraperitoneal injection of 5% chloral hydrate (5 mL / kg);

[0030] (3) Fix the mouse vertically and use sterilized tweezers to clamp the mouse's nose to force it to breathe through its mouth;

[0031] (4) Use tweezers to pull the front half of the mouse's tongue out of the mouth, and use a pipette to inject 50 μL of BLM solution (or PBS) into the mouse's throat;

[0032] (5) After the mice showed obvious respiratory movements in their chest cavity (ensuring BLM was inhaled into the trachea) for about 25 seconds, they were placed back in their cages and laid flat. After resuscitation, the mice in the BLM-treated group were randomly divided into two groups: the BLM group and the BLM+AX group. The BLM+AX group was administered AX (200 mg / kg / day) via drinking water from the tenth day of modeling until the 21st day when the mice were sacrificed and their lungs were harvested. For the BLM group mice, from the tenth day of modeling until the 21st day when the mice were sacrificed and their lungs were harvested, they were fed the same volume of water via drinking water.

[0033] Twenty-one days after bleomycin instillation, mice were anesthetized by intraperitoneal injection of 5% chloral hydrate (10 mL / kg), blood was collected from the eyeballs, and the lungs were removed by exposing the thoracic cavity with surgical scissors. The lungs were washed twice with PBS and then directly placed in liquid nitrogen at -80°C for hydroxyproline analysis or mRNA level analysis. Alternatively, an appropriate amount of 4% PFA was injected into the trachea and the lungs were fixed in pre-prepared 4% PFA for 24 hours. After appropriate treatment, the lung tissue was embedded in paraffin, sectioned, and then subjected to histological staining or histoimmunological analysis.

[0034] Example 2 Paraffin embedding and sectioning: (1) The fixed lung tissue was removed and placed in a dehydrator for dehydration according to the following steps:

[0035] Reagent time

[0036] 70% ethanol for 20 min

[0037] 80% ethanol for 20 min

[0038] 90% ethanol for 20 min

[0039] 95% ethanol for 20 min

[0040] 100% ethanol I 10 min

[0041] 100% Ethanol II 10 min

[0042] (2) The dehydrated lung tissue was subjected to paraffin permeation treatment:

[0043] Reagent time

[0044] xylene 5 min

[0045] Xylene I 5 min

[0046] Xylene II 5 min

[0047] Paraffin wax (70℃) for 20 min

[0048] Paraffin I (70℃) 1 h

[0049] Paraffin II (70℃) 12 h

[0050] (3) Place the lungs into an embedding frame containing molten paraffin. After the paraffin cools and solidifies into a block, label the wax block.

[0051] (4) Cut 3-4 pieces of wax block continuously with a slicer, keeping the thickness at 5μm. Place them in a 42℃ water bath for spreading, lift them out with a glass slide, bake them to fix them for later use.

[0052] Example 3 Hydroxyproline detection: (1) Take out the lung tissue frozen at -80℃ and put the lung tissue into a 2mL EP tube (containing 1mL PBS with protease inhibitor and magnetic beads). Grind it on ice. After grinding, take 500uL of lung tissue homogenate and put it into a glass vial. Add 12N HCl to 1mL. Put the glass vial into a 125℃ oven for 24h. Add 6N HCl to 1mL every 3h.

[0053] (2) Prepare chloramine T solution and Ehrlich reagent according to the following systems respectively. Chloramine T solution and Ehrlich solution should be prepared and used immediately and stored away from light;

[0054] Chlorine T solution:

[0055] Chloramine T 0.282g

[0056] 2 mL of n-propanol

[0057] 2mL of distilled water

[0058] 16 mL of citric acid-acetic acid buffer solution

[0059] Ehrlich's solution:

[0060] 2.5g of 4-DMAB Ehrlich's reagent

[0061] 9.3 mL of n-propanol

[0062] 3.9 mL of 70% perchloric acid

[0063] (3) Dilute hydroxyproline standard: 400ug / mL hydroxyproline is serially diluted to different concentrations.

[0064] (4) After cooling each glass vial, mix them thoroughly. Take 5 μL of lung tissue suspension from each vial and place it into a 96-well plate, with three replicate wells for each sample. Add 5 μL of citrate-acetate buffer to each well.

[0065] (5) Add 100 μL of chloramine T solution to each well and let stand in the dark for 30 min.

[0066] (6) Finally, add 100 μL of Ehrlich reagent to each well and place it in a 65°C oven for 30 min.

[0067] (7) Place the 96-well plate into the microplate reader and measure the absorbance at 550 nm.

[0068] Masson staining was performed on sections of harvested mouse lungs, and collagen deposition, tracheal wall thickness, and Ashcroft score were statistically analyzed. The results showed that AX treatment from day 10 to day 21 after bleomycin perfusion inhibited BLM-induced pulmonary fibrosis. Figure 1 As shown in AD, compared to control mice perfused with PBS, BLM-induced lung fibrosis was observed in mice. Specifically, this manifested as increased deposition of extracellular matrix components such as collagen fibers, thickening of the tracheal wall, and destruction of normal alveolar structure. Figure 1 A). For control mice perfused with PBS, BLM-induced mouse fibrosis parameters, including lung fibrosis fraction ( Figure 1 B) Collagen deposition ( Figure 1 C) Tracheal wall thickness ( Figure 1 All parameters (D) were significantly elevated, while these parameters were significantly reduced after AX treatment. Furthermore, in control mice perfused with PBS, the hydroxyproline content in the fibrotic lungs of mice with BLM-induced fibrosis was significantly elevated, while it was significantly reduced after AX treatment. Figure 1 E).

[0069] Example 4 Immunofluorescence staining: (1) Paraffin sections of the lungs were dehydrated by treatment with xylene and gradient alcohols;

[0070] Reagent time

[0071] Xylene I 20 min

[0072] Xylene II 10 min

[0073] 100% ethanol I 5 min

[0074] 100% ethanol I 3 min

[0075] 95% ethanol for 2 min

[0076] 80% ethanol for 1 min

[0077] 70% alcohol for 1 min

[0078] ddH2O 5-10s

[0079] (2) Place the tissue sections into a repair box filled with 1×citric acid antigen repair solution and place it in a microwave oven for repair. Do not dry the sections during this process. After cooling naturally, wash with PBS 3 times, 3 minutes each time.

[0080] medium heat 8 min

[0081] Ceasefire 8 min

[0082] Low heat for 7 minutes

[0083] (3) Use a brush to draw circles around the tissue, and add 2% BSA inside the circles. Seal at 37℃ for 30 minutes.

[0084] (4) After removing the blocking solution, add a certain proportion of diluted primary antibody to the slide, incubate in a humidified chamber at 4°C, and rinse with PBS 3 times for 5 min each time. After slightly drying the slide, add fluorescent secondary antibody to cover the tissue and incubate in the dark for 1 h. Rinse with PBS 3 times for 3 min each time;

[0085] Note: If only one antibody is stained by immunofluorescence, skip steps (5)-(7); if two antibodies are used, proceed with steps (5)-(7):

[0086] (5) Add FITC reagent to the circle, incubate in the dark for 10 min, wash 3 times with TBST for 3 min each time.

[0087] (6) Place the tissue sections in a humidified box filled with citric acid antigen retrieval solution and heat in a microwave oven (repeat step 2). Do not dry the sections to remove the antibodies bound to the tissue.

[0088] (7) Drop a certain proportion of diluted second primary antibody onto the slide, incubate overnight at 4°C in a humidified chamber, wash 3 times with PBS for 3 min each time, shake dry slightly, add fluorescent secondary antibody, and incubate at room temperature in the dark for 1 h.

[0089] (8) After gently shaking off the water, add the autofluorescence quencher, incubate for 5 min, and wash with distilled water for 10 min;

[0090] (9) After slightly drying, add DAPI nuclear staining solution to the center of the slice and incubate in the dark for 5 minutes;

[0091] (10) Wash the sections three times with PBS for 3 minutes each time, gently shake dry, and mount. Observe under a fluorescence microscope, take pictures at 200× and collect images.

[0092] A mouse model of pulmonary fibrosis was established by administering 1.5 Units / kg of BLM to male C57BL / 6 mice aged 8-13 weeks via endotracheal instillation. A randomized subset of mice were administered AX (200 mg / kg) once daily by gavage from day 10 to day 21 following BLM instillation. Male C57BL / 6 mice aged 8-13 weeks that received an equal volume of PBS via endotracheal instillation served as controls. Figure 2 Figure A shows that the collagen I content in the lungs of mice with BLM-induced pulmonary fibrosis is elevated, and the collagen I content decreases after treatment with AX. Figure B shows the quantitative analysis of the relative signal intensity of collagen in immunofluorescence using ImageJ. Figure 2 Figure C shows that the α-Sma content in the lungs of mice with BLM-induced pulmonary fibrosis is increased, and the α-Sma level decreases after AX treatment. Figure D shows the quantitative analysis of the relative signal intensity of α-Sma in immunofluorescence using ImageJ. Figure 3A showed that the immunofluorescence signal of S100a8 in the lungs of mice with BLM-induced pulmonary fibrosis was increased, while the immunofluorescence signal of S100a8 was decreased after the addition of AX treatment. Figure 5 Immunofluorescence staining results showed that, compared with PBS control mice, Ccsp in BLM-induced pulmonary fibrosis model mice was significantly lower. + (Clara cell secretory protein) The lung airway epithelial cells are partially missing, but the loss of airway epithelial cells is significantly improved after AX treatment.

[0093] Example 5: Determination of mRNA levels: (1) Lung tissue was taken out from a -80℃ refrigerator and placed in a 2mL EP tube. 1mL PBS and two magnetic beads were added and the tissue was ground. After grinding, 100uL of lung tissue homogenate was taken to extract total RNA. RNA was extracted from lung tissue or cells using an RNA kit (FOREGENE). After the concentration was measured, cDNA was reverse transcribed using a reverse transcription kit (novoprotein).

[0094] (2) Real-Time PCR

[0095] Configure the PCR reaction system as follows, with three replicate wells for each sample:

[0096] Component Volume (μL)

[0097] 1xSYBR Green PCR Mix 10

[0098] Primer Forward 0.5

[0099] Primer Reverse 0.5

[0100] Template DNA 2.0

[0101] ddH2O 7.0

[0102] Total Volume 20

[0103] The above reaction system was used to amplify cDNA using a real-time fluorescence PCR instrument.

[0104] Results analysis: Using β-actin as an internal control, according to 2 -(delta(deltaCt)) The method was used to analyze the results and obtain the mRNA levels of the detected genes in different samples.

[0105] Figure 3 B shows that, in control mice perfused with PBS, BLM-induced fibrotic lung tissue... S100a8Transcript levels were significantly elevated, but significantly decreased after AX treatment.

[0106] Compared to untreated human lung fibroblasts, treatment with 3.5 μg / L TGF-β1 resulted in a fusion rate of approximately 30%. After 24 hours, cell viability significantly increased using the MTT assay / cytotoxicity assay / cell proliferation assay kit (Solarbio, M1020) following the manufacturer's instructions. Compared to TGF-β1-treated cells, simultaneous treatment with 10 μg / ml AX and 3.5 μg / L TGF-β1 for 24 hours significantly decreased cell viability. Furthermore, compared to untreated human lung fibroblasts, treatment with AX alone at concentrations of 0.5, 1, 2.5, 5, 10, 20, 40, 80, and 160 μg / ml for 24 hours had no significant effect on cell viability. Figure 4 As shown.

[0107] Example 6 Immunohistochemistry: (1) Dewaxing paraffin sections to water: Soak the sections in the following reagents in sequence, and finally wash with distilled water.

[0108] Reagent time

[0109] Environmentally friendly dewaxing solution I 10min

[0110] Environmentally friendly dewaxing solution II 10min

[0111] Environmentally friendly dewaxing solution III 10min

[0112] Anhydrous ethanol I 5 min

[0113] Anhydrous ethanol II 5 min

[0114] Anhydrous ethanol III 5 min

[0115] (2) Antigen retrieval: After natural cooling, place the slide in PBS (pH 7.4) and wash it three times on a decolorizing shaker for 5 minutes each time.

[0116] (3) Blocking endogenous peroxidase: Place the slide in 3% hydrogen peroxide solution and incubate at room temperature in the dark for 25 min. Then place the slide in PBS (pH 7.4) and wash it three times on a decolorizing shaker for 5 min each time.

[0117] (4) Serum blocking: Add 3% BSA to the histochemistry zone and evenly cover the tissue. Block at room temperature for 30 min. (Use rabbit serum to block if the primary antibody is of goat origin, and use BSA to block if it is of other origin).

[0118] A mouse model of pulmonary fibrosis was established by administering BLM (1.5 Units / kg) to 8-13 week old male C57BL / 6 mice via endotracheal instillation. A randomized subset of mice were then administered AX (200 mg / kg) daily by gavage from day 10 to day 21 after BLM instillation. In the control model, 8-13 week old male C57BL / 6 mice administered an equal volume of PBS via endotracheal instillation were used. Compared to the PBS-infused control mice, immunohistochemical results showed significant aggregation of macrophages (marker F4 / 80) and mature T lymphocytes (marker CD3) in the lungs of the BLM-induced pulmonary fibrosis model mice. AX treatment significantly reduced their expression, and AX treatment alone did not result in significant inflammatory cell infiltration. Figure 6 As shown.

[0119] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0120] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Application of arabinoxylan as the sole active ingredient in the preparation of drugs for treating pulmonary fibrosis.

2. The application according to claim 1, characterized in that, Arabic xylan significantly reduced the degree of collagen deposition, pulmonary fibrosis fraction, tracheal deposition thickness and hydroxyproline content in the lungs of bleomycin-induced pulmonary fibrosis mice, improved the survival rate and body weight of bleomycin-induced pulmonary fibrosis mice, and reduced the lung wet weight / body weight ratio of bleomycin-induced pulmonary fibrosis mice.

3. The application according to claim 1, characterized in that, Arabica xylan can downregulate the expression levels of collagen I and α-Sma in bleomycin-induced pulmonary fibrosis lung tissue of mice.

4. The application according to claim 1, characterized in that, Arabicaxylan can downregulate the expression level of S100a8 in bleomycin-induced pulmonary fibrosis lung tissue of mice.

5. The application according to claim 1, characterized in that, Arabica xylan can downregulate the proliferation level of TGF-β1-induced human lung fibroblasts.

6. The application according to claim 1, characterized in that, Arabica xylan can improve the loss of airway epithelial cells in fibrotic lung tissue of mice after bleomycin induction.

7. The application according to claim 1, characterized in that, Arabica xylan can downregulate the infiltration of inflammatory cells in the lung tissue of mice with bleomycin-induced pulmonary fibrosis.

Images