Application of chemokine ligand 4 antibody in preparation of medicine for treating silicosis

Abstract

The invention discloses an application of a chemokine ligand 4 antibody in preparation of a medicine for treating silicosis, C-Cchemmokine ligand 4, namely the chemokine ligand 4 is called a CCL4 antibody for short, silicosis is lung diseases caused by long-term inhalation of free crystalline silicon dioxide particles in air, and is mainly characterized by inflammation and fibrosis. The treatment mechanism of silicosis and the side effects brought by the silicosis are very complex, the silicosis is progressive and irreversible and still has no curing scheme, so that the silicosis still has great threats to the life quality and the life time of silicosis patients, and the silicosis can damage the hematopoietic system of the organism besides causing inflammation and fibrosis, so that the silicosis cannot be cured. The invention discloses an inhibitor CCL4 antibody which can effectively relieve inflammation and fibrosis reaction caused by silicosis and can also recover the function of a hematopoietic system, and the number and function of hematopoietic stem progenitor cells are mainly influenced by the hematopoietic stem progenitor cells caused by silicosis caused by the hematopoietic stem progenitor cells.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to application of a chemokine ligand 4 antibody in preparation of a drug for treating silicosis. BACKGROUND

[0002] Silica (SiO2) is a widely existing mineral and belongs to the components of the earth's crust. SiO2 can be mainly divided into two categories (crystalline and amorphous), and among them, crystalline silica (cSiO2) is more invasive to the body. Due to occupational needs, part of the population inevitably inhales SiO2, mainly including mining, metallurgy and automobile manufacturing, glass, porcelain or ceramic tile industry; in addition, there is SiO2 exposure in the emerging process of jewelry manufacturing, artificial stone processing and cowboy cloth sandblasting. Silicosis is a lung disease caused by long-term inhalation of free cSiO2 in the air, and its main characteristics are inflammation and fibrosis. On the other hand, clinical studies show that in addition to inflammation and fibrosis, the content of peripheral blood lymphocytes and platelets of silicosis patients decreases significantly, suggesting that the hematopoietic system is also affected.

[0003] The pathogenesis and side effects of silicosis are very complex. The current treatment method focuses on prevention, supplemented by lung washing, oxygen inhalation, anti-inflammation, anti-fibrosis and stem cell therapy; among them, performing a healthy lung transplantation on patients has a relatively significant effect, but it is not applicable due to the tight supply of lung sources, high price and complex operation. Due to the strengthened management of air pollution, the incidence of silicosis has decreased, but because silicosis is progressive and irreversible, and there is still no cure, the quality of life and survival time of silicosis patients are still a great threat.

[0004] In addition, a number of studies have shown that the lung is also one of the hematopoietic organs, and there are a large number of megakaryocytes in the lung, which dynamically release platelets. Further through single-cell sequencing analysis, researchers believe that lung megakaryocytes are different from bone marrow megakaryocytes, are rich in maturation markers (tend to platelet production) and have immune and inflammatory characteristics. At the same time, megakaryocytes, as hematopoietic stem cell niches, have a regulatory effect on the rest and function of hematopoietic stem cells (HSC). Notably, researchers have also found functional hematopoietic stem and progenitor cells in the extravascular space of the lung. In the case of hematopoietic damage or platelet deficiency in the body, megakaryocyte HSPCs can migrate from the lung, refill the bone marrow, and complete platelet reconstruction, restoring hematopoietic system function. Therefore, it is worth further exploring whether cSiO2 and silicosis have an impact on the body's hematopoietic system.

[0005] In summary, the present application constructs a silicosis model by administering cSiO2 to the lungs of mice. Experimental results show that megakaryocytes play a key role after cSiO2 intake, and regulate the number and function of lung HSPCs through the CCL4 pathway. At the same time, by inhibiting this signaling pathway through CCL4 antibody, inflammation and fibrosis can be reduced and the function of the hematopoietic system can be restored. Based on the above scientific basis, the present application first proposes that the CCL4 antibody can alleviate various symptoms of silicosis, and is expected to fill the existing treatment gap. SUMMARY

[0006] Technical problems solved:

[0007] The present application solves the technical defects in the prior art that silicosis is progressive and irreversible, there is no simple and effective treatment for silicosis, and there is still no cure, and provides a use of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, which verifies the effect of the CCL4 antibody from inflammation, fibrosis, and hematopoietic damage.

[0008] Technical scheme:

[0009] A use of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis.

[0010] Preferably, the drug for treating silicosis is specifically a drug for treating inflammation, fibrosis, and hematopoietic function damage caused by silicosis.

[0011] Preferably, the drug comprises a chemokine ligand 4 antibody and a pharmaceutically acceptable excipient.

[0012] Preferably, the excipient is one or more of a diluent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption promoter, a surfactant, an adsorption carrier, and a lubricant.

[0013] Preferably, the drug is an injection or a non-injection.

[0014] Preferably, the dose of the injection is 1.2 μg / 100 μL.

[0015] Preferably, the injection is injected through the tail vein once a week for a total of 4 weeks.

[0016] Preferably, the drug is a tablet, a capsule, a powder, a pill, a granule, a solution, a suspension, a syrup, an injection, a suppository, an adsorbent, or a spray.

[0017] Advantages

[0018] 1. The chemokine ligand 4 antibody of the present application can effectively alleviate lung inflammation caused by silicosis by inhibiting CCL4.

[0019] 2. The chemokine ligand 4 antibody of the present application can effectively alleviate the pulmonary fibrosis caused by silicosis by inhibiting CCL4;

[0020] 3. The chemokine ligand 4 antibody of the present application can effectively increase the proportion of damaged lung hematopoietic stem and progenitor cells by inhibiting CCL4;

[0021] 4. The chemokine ligand 4 antibody of the present application can effectively reduce the apoptosis rate of damaged lung hematopoietic stem and progenitor cells by inhibiting CCL4;

[0022] 5. The chemokine ligand 4 antibody of the present application can effectively restore the proportion of damaged bone marrow hematopoietic stem cells by inhibiting CCL4;

[0023] 6. The chemokine ligand 4 antibody of the present application can effectively increase the absolute number of damaged bone marrow hematopoietic stem cells by inhibiting CCL4;

[0024] 7. The chemokine ligand 4 antibody of the present application can effectively reduce the apoptosis rate of damaged bone marrow hematopoietic stem cells by inhibiting CCL4. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 Figure 1 is a diagram showing that long-term intake of cSi02inhibits lung HSPCs in mice of the present application, wherein a is a representative flow chart of lung progenitor cells and HSPCs in mice; b is a proportion chart of progenitor cells and HSPCs; c is a representative flow chart of HSPC apoptosis; d is a statistical chart of the apoptosis rate of progenitor cells and HSPCs; e is a lung HSPC transplantation model chart, n = 5 in each group; f is a representative flow chart of the proportion of peripheral blood platelets; g is a statistical chart of the proportion of peripheral blood platelets;

[0026] Figure 2 Figure 1 is a diagram showing that long-term intake of cSi02inhibits lung HSPCs in mice of the present application, wherein a is a representative flow chart of lung progenitor cells and HSPCs in mice; b is a proportion chart of progenitor cells and HSPCs; c is a representative flow chart of HSPC apoptosis; d is a statistical chart of the apoptosis rate of progenitor cells and HSPCs; e is a lung HSPC transplantation model chart, n = 5 in each group; f is a representative flow chart of the proportion of peripheral blood platelets; g is a statistical chart of the proportion of peripheral blood platelets;

[0027] Figure 3 Figure 1 is a diagram showing that long-term intake of cSi02inhibits lung HSPCs in mice of the present application, wherein a is a representative flow chart of lung progenitor cells and HSPCs in mice; b is a proportion chart of progenitor cells and HSPCs; c is a representative flow chart of HSPC apoptosis; d is a statistical chart of the apoptosis rate of progenitor cells and HSPCs; e is a lung HSPC transplantation model chart, n = 5 in each group; f is a representative flow chart of the proportion of peripheral blood platelets; g is a statistical chart of the proportion of peripheral blood platelets;

[0028] Figure 4 Figure showing the changes in the levels of inflammation and fibrosis in mice after tail vein injection of CCL4 antibody;

[0029] Figure 5 Figure showing the changes in the proportion, number, and apoptosis and cell cycle of lung hematopoietic stem and progenitor cells in mice after tail vein injection of CCL4 antibody, wherein the left graph shows the proportion of lung hematopoietic stem and progenitor cells after inhibition of CCL4 to restore lung hematopoietic stem and progenitor cell function, and the right graph shows the apoptosis rate of lung hematopoietic stem and progenitor cells after inhibition of CCL4 to restore lung hematopoietic stem and progenitor cell function;

[0030] Figure 6 Figure showing the changes in the proportion, number, and apoptosis and cell cycle of bone marrow hematopoietic stem and progenitor cells in mice after tail vein injection of CCL4 antibody, wherein a is a representative flow cytometry graph of bone marrow LT-HSCs, ST-HSCs, MPP2s, and MPP3 / 4s, b is a graph of cell number (m), and c is a graph of the apoptosis rate of hematopoietic stem cells. DETAILED DESCRIPTION

[0031] The application will be described in detail below with specific embodiments. The following examples will help those skilled in the art to further understand the application, but do not limit the application in any form. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the application. These are within the scope of protection of the application.

[0032] Example 1

[0033] Application of a CCL4 antibody in the preparation of a drug for treating silicosis, mouse silicosis model construction, the specific steps are as follows:

[0034] The purchased normal C57BL / 6J (CD45.2) mice were randomly divided into control and silicosis groups (5 mice in each group). First, the mice were anesthetized with 300 μL of anesthetic intraperitoneal injection; 3 minutes later, the mouse body was hung, and the tongue was gently pulled out; 40 μL of cSiO2 solution (1 mg) was dropped into the mouse lung through tracheal instillation; once a week, for a total of 4 weeks; the model establishment includes a 4-week modeling period and an 8-week waiting period. Eight weeks later, the mice were euthanized and analyzed.

[0035] CCL4 antibody treatment model: silicosis model was constructed according to the above method, and 1.2 μg / 100 μL CCL4 antibody was injected into the mouse tail vein, once a week for a total of four weeks. At the 12th week, the mice were euthanized and analyzed.

[0036] Example 2

[0037] Application of a CCL4 antibody in the preparation of a drug for treating silicosis, mouse lung lavage fluid and single nuclear cell acquisition, the specific steps are as follows:

[0038] Lung lavage fluid:

[0039] First step: fix the euthanized mouse on the foam board, expose the trachea of the mouse neck with scissors and forceps; second step: cut a small hole in the trachea of the mouse transversely with scissors, carefully insert a 12-gauge flat needle, and tie the flat needle and the trachea with cotton thread;

[0040] Third step: suck 1 mL of PBS containing 2% FBS into a 1 mL syringe, insert the flat needle, and slowly push the liquid into the mouse lung;

[0041] Fourth step: after waiting for 1 minute, slowly suck out the liquid to obtain the lung lavage fluid. The final volume of the lavage fluid is 600-800 μL.

[0042] Lung mononuclear cells:

[0043] S1: cut the mouse lung tissue in a centrifuge tube, digest with 1 mL of mouse lung cell digestion solution at 37°C for 30 minutes, and invert the centrifuge tube once at 15 minutes;

[0044] S2: filter with a 70 μm filter, centrifuge at 4°C and 400g for 5 minutes, and discard the supernatant;

[0045] S3: add 2 mL of red blood cell lysis solution, lyse for 5 minutes, and then add twice the volume of PBS containing 2% FBS to terminate lysis;

[0046] S4: centrifuge at 4°C and 400g for 5 minutes, discard the supernatant, add 1 mL of PBS containing 2% FBS, and count.

[0047] Example 3

[0048] Application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, hematoxylin and eosin (H&E) staining, the specific steps are as follows:

[0049] First step: after the mouse lung is removed, it is first fixed in 4% formaldehyde for 6 hours;

[0050] Second step, dehydration: after washing with PBS, use ethanol solution gradient (70%, 80%, 95%) for 1 hour each; replace the fresh 95% ethanol solution and soak for 2 hours twice; dehydrate with 100% ethanol solution for 1 hour; finally, replace the fresh ethanol solution (100%) and soak for 2 hours;

[0051] Third step, wax immersion: soak the sample in dimethylbenzene I for 10 minutes and dimethylbenzene II for 20 minutes; after the tissue is transparent, place it in melted paraffin for 1 hour, and repeat the above steps 3 times;

[0052] Fourth step, embedding section: paraffin embedding using embedding machine, and cutting into 4 μm thickness, 37℃ baking 4 hours;

[0053] Fifth step, deparaffinization: paraffin section in xylene I soak 20 minutes, then move into xylene II soak 20 minutes; after paraffin dissolves, 100% ethanol soak 5 minutes, repeat twice, finally with sterile water soak 5 minutes;

[0054] Sixth step, staining: section into staining rod, hematoxylin staining 5 minutes, water washing until section colorless; differentiation liquid and return blue liquid each staining 3-5 seconds, fast water washing; finally, in the following solution in turn soak 5 minutes (85% ethanol, 90% ethanol, eosin, 100% ethanol, n-butanol, xylene I and xylene II);

[0055] Seventh step, mounting: section air drying, using resin mounting;

[0056] Eighth step: using optical microscope observation.

[0057] Example 4

[0058] The application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, mouse lung Masson staining, the specific steps are as follows:

[0059] First step: sample preparation, dehydration, wax immersion, embedding section and deparaffinization process are consistent with H&E sample preparation process; second step, staining: section is placed in Masson dye 1 overnight incubation;

[0060] Third step: take out the section, and wash the section fast with water until colorless;

[0061] Fourth step: section is placed in Masson dye 2 (Lichun red, preheated at 65℃ for 30 minutes before staining) staining 3-5 minutes, and washed with water 2-3 times;

[0062] Fifth step: section is placed in Masson dye 3 (phosphomolybdic acid) staining 30-60 seconds;

[0063] Sixth step: take out the section, slightly drain, and dye in Masson dye 4 (benzamine blue, preheated at 65℃ for 30 minutes before staining) 5-20 seconds;

[0064] Seventh step: section into 1% glacial acetic acid, differentiate for several seconds, three cylinders, and differentiate 5-10 seconds in each cylinder;

[0065] Eighth step, dehydration: section is placed in three cylinders containing anhydrous ethanol, 5-10 seconds in each cylinder; then put into n-butanol for 10-20 seconds;

[0066] Step 9, cover the slice: put the slice into xylene I for 5 minutes, then into xylene II for 5 minutes; dry quickly at the air outlet and cover the slice with neutral gum.

[0067] Example 5

[0068] The application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, mouse lung immunohistochemistry, the specific steps are as follows:

[0069] Step 1: sample preparation, dehydration, wax immersion, embedding sectioning and dewaxing process are consistent with the description above;

[0070] Step 2, antigen repair: take citric acid repair solution and heat to boiling, put the slice into the pressure cooker, heat for 3 minutes, open the exhaust valve; after cooling, shake the slice in PBS, wash the slice, repeat 3 times, 5 minutes each time;

[0071] Step 3, endogenous enzyme blocking: put the slice into 3% H2O2 aqueous solution, incubate at room temperature for 20 minutes, PBS wash 3 times, 5 minutes each time;

[0072] Step 4, serum blocking: mark the tissue around with the histological pen, and drop serum on the tissue, incubate at 37℃ for 30 minutes;

[0073] Step 5, primary antibody incubation: dilute the antibody (F4 / 80 and fibronectin) with antibody diluent, shake off the serum on the slice, and drop the antibody diluent on the tissue, incubate at 4℃ overnight;

[0074] Step 6, secondary antibody incubation: prepare the secondary antibody with phosphate buffer, drop the secondary antibody solution on the tissue, incubate at 37℃ for 1 hour, wash the slice with buffer 3 times, 5 minutes each time;

[0075] Step 7, DAB color development: drop DAB solution on the tissue, observe under the microscope, after specific brown expression appears, wash off the DAB color development solution on the tissue, and soak the slice in water;

[0076] Step 8, re-stain with hematoxylin: put the slice into hematoxylin dyeing solution, dye for 3-5 minutes, wash the excess hematoxylin dyeing solution on the tissue with water, after the nucleus turns blue, put the slice into 0.5% hydrochloric acid alcohol differentiation solution, differentiate for 1-2 seconds, then wash with water; put the glass slice into the anti-blue solution, soak for 3-5 seconds, then wash with water (nucleus is blue, and there is no obvious blue color in the rest of the position);

[0077] Ninth step, dehydration, mounting: the slices are placed in the dye vat containing anhydrous ethanol 1, anhydrous ethanol 2, anhydrous ethanol 3, n-butanol 1, n-butanol 2, xylene 1, xylene 2 in turn, each vat is soaked for 5 minutes; then the slices are taken out and air dried, an appropriate amount of neutral gum is added on the tissue, a cover glass is covered, and it is dried.

[0078] Example 6

[0079] The application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, hydroxyproline content detection, the specific steps are as follows:

[0080] First step: weigh 0.1 g of sample in a centrifuge tube, and cut the tissue as much as possible to facilitate subsequent digestion;

[0081] Second step: add 1 mL of 6 mol / L hydrochloric acid solution, 100℃, metal bath 2-6 hours, digest until there are no obvious lumps;

[0082] Third step: after cooling, adjust the pH value of the solution with 10 mol / L NaOH and detect it with a pH meter, so that the pH value of the lung long-term silica exposure inhibits the function of the hematopoietic system in silicosis mice is between 6-8, and the volume is adjusted to 2 mL with sterile water;

[0083] Fourth step: 16000g, 25℃, centrifuge for 20 minutes, take the supernatant for detection;

[0084] Fifth step: add 60 μL of sample and 60 μL of chloramine T to each well, mix well, and stand at room temperature for 20 minutes;

[0085] Sixth step: add 60 μL of dimethylbenzaldehyde and 120 μL of sterile water to the above solution, mix well, 60℃, 20 minutes, take out and stand at room temperature for 15 minutes;

[0086] Seventh step: take 200 μL of liquid in a 96-well plate and detect the absorbance at 560 nm.

[0087] Example 7

[0088] The application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis, mouse lung HSPCs transplantation experiment, the specific steps are as follows:

[0089] First step: euthanize the mice from the control and cSiO2 treatment groups;

[0090] Second step: take the lung cells of the mice, digest and separate to obtain single nucleus cells;

[0091] Third step: sort 2000 HSPCs cells from each group, and inject them into the recipient Mpl knockout mice through the tail vein;

[0092] Fourth step: 4 weeks later, detect the proportion and number of platelets in peripheral blood.

[0093] Example 8

[0094] Use of a CCL4 antibody in the preparation of a drug for treating silicosis, mouse bone marrow cell extraction, the specific steps are as follows:

[0095] First step: take the hind legs of the mouse and put them in the alcohol in the six-well plate;

[0096] Second step: place the thigh bone in the six-well plate containing 2% FBS PBS, and cut off both ends;

[0097] Third step: use a 3mL syringe to suck the 2% FBS PBS to gently blow out the bone marrow, and use a 1mL pipette to blow the cells;

[0098] Fourth step: filter through a 70μm filter screen;

[0099] Fifth step: 4℃, 1500rpm, 5 minutes, centrifuge and discard the supernatant;

[0100] Sixth step: after lysing for 3 minutes (3mL per mouse) with red blood cell lysis solution, blow the cells evenly;

[0101] Seventh step: add twice the volume of 2% FBS PBS (6mL per mouse) and mix well to stop lysis;

[0102] Eighth step: filter through a 70μm filter screen;

[0103] Ninth step: 4℃, 400g, 5 minutes, centrifuge and discard the supernatant;

[0104] Tenth step: resuspend the cells with 1mL of 2% FBS PBS, mix well, and take 1μL for cell counting.

[0105] Example 9

[0106] Use of a CCL4 antibody in the preparation of a drug for treating silicosis, flow cytometry detection, the specific steps are as follows:

[0107] After obtaining mouse mononuclear cells, the corresponding antibody was added, and the cells were incubated at 4°C in the dark for 30-45 minutes; 1 mL of PBS containing 2% FBS was added to resuspend the cells, which were centrifuged at 4°C at 400g for 5 minutes, and the supernatant was discarded; finally, 200 μL of PBS containing 2% FBS was added to resuspend the cells, which were filtered through a 70 μm filter screen before being detected on the machine. HSCs staining: 5e6 cells were taken, and 7 μL of antibody combination (Lineage, Sca1, c-Kit, CD150, CD48) was added; the Lineage was composed of CD3e, CD4, CD8a, CD45R, IgM, Mac-1, Gr-1, Ter-119, etc.

[0108] Apoptosis detection:

[0109] First step: the cells first completed the first step of staining (HSC antibody combination), and then 1 mL of apoptosis buffer was added to resuspend the cells, which were centrifuged at 4°C at 400g, and the supernatant was discarded;

[0110] Second step: the cells were resuspended with 200 μL of apoptosis buffer, and 5 μL of AnnexinV was added to each 5e6 cells, which were stained at 4°C in the dark for 30 minutes;

[0111] Third step: the cells were resuspended with 1 mL of apoptosis buffer, which were centrifuged at 4°C at 400g, and the supernatant was discarded;

[0112] Fourth step: the cells were resuspended with 200 μL of buffer, filtered through a 70 μm filter screen, and detected on the machine. Apoptotic cells were the AnnexinV positive cell population.

[0113] As shown in Figure 1 , the intake of cSiO2 caused lung inflammation and fibrosis. Among them, a, representative pictures of lung and H&E staining, Masson staining and immunohistochemistry of F4 / 80 and FN, scale bar: 200 μm. b is a representative flow chart of macrophages and neutrophils in lung lavage fluid; c is a bar chart of the proportion of macrophages and neutrophils in lung lavage fluid; d is a bar chart of the absolute number of macrophages and neutrophils in lung lavage fluid; e is a bar chart of lung hydroxyproline content. By constructing a mouse model, it is proved that long-term inhalation of silica particles can cause lung inflammation and fibrosis.

[0114] As shown in Figure 2 , the intake of cSiO2 inhibited HSPCs in the lungs of mice. Among them, a is a representative flow chart of HSPCs and progenitor cells in the lungs of mice; b is a bar chart of the proportion of HSPCs and progenitor cells; c is a representative flow chart of HSPC apoptosis; d is a statistical chart of the apoptosis rate of HSPCs and progenitor cells; e is a chart of lung HSPC transplantation model, n=5 in each group; f is a representative flow chart of the proportion of peripheral blood platelets; g is a statistical chart of the proportion of peripheral blood platelets. Long-term inhalation of silica particles can cause damage to lung hematopoietic stem and progenitor cells.

[0115] like Figure 3 As shown, the function of hematopoietic stem cells (HSCs) in mouse bone marrow was inhibited by cSiO2 ingested through the lungs. Figure a shows a representative flow cytometry plot of the corresponding bone marrow cells; figure b shows the proportions of LT-HSCs, ST-HSCs, MPP2s, and MPP3 / 4s; and figure c shows the absolute numbers of LT-HSCs, ST-HSCs, MPP2s, and MPP3 / 4s. Long-term inhalation of silica particles can damage bone marrow hematopoietic progenitor cells.

[0116] like Figure 4 As shown, inhibiting CCL4 reduces lung inflammation and fibrosis. Lung tissue and H&E staining and Masson staining are also included.

[0117] like Figure 5 As shown, Figure 5 The figures show the proportion, number, apoptosis, and cell cycle changes of hematopoietic stem and progenitor cells in the lungs of mice after tail vein injection of CCL4 antibody. The left figure shows the ratio of lung progenitor cells to HSPCs in the recovery of lung hematopoietic stem and progenitor cell function by inhibiting CCL4; the right figure shows the apoptosis rate in the recovery of lung hematopoietic stem and progenitor cell function by inhibiting CCL4.

[0118] like Figure 6 As shown, Figure 6 The figures show the proportion, number, apoptosis, and cell cycle changes of hematopoietic stem and progenitor cells in mouse bone marrow after tail vein injection of CCL4 antibody. Figure a shows representative flow cytometry plots of bone marrow LT-HSCs, ST-HSCs, MPP2s, and MPP3 / 4s; figure b shows the cell number (m); and figure c shows the apoptosis rate of hematopoietic stem cells, indicating that inhibiting CCL4 restores bone marrow hematopoietic stem cell function.

[0119] The embodiments selected in the above materials are for ease of understanding and not for limiting the process method. Those skilled in the art can easily modify the process flow or transfer it to other cases without inventive change. If these modifications also fall under the category of similar claims or similar technology of this invention, then the intent of this invention also includes these modifications.

Claims

1. Application of a chemokine ligand 4 antibody in the preparation of a drug for treating silicosis.

2. The use of the chemokine ligand 4 antibody according to claim 1 in the preparation of a drug for treating silicosis, characterized in that: The drugs mentioned for treating silicosis are specifically drugs used to treat inflammation, fibrosis, and hematopoietic dysfunction caused by silicosis.

3. The use of the chemokine ligand 4 antibody according to claim 1 in the preparation of a drug for treating silicosis, characterized in that: The drug includes a chemokine ligand 4 antibody and pharmaceutically acceptable excipients.

4. The use of the chemokine ligand 4 antibody according to claim 3 in the preparation of a drug for treating silicosis, characterized in that: The excipients are one or more of the following: diluent, excipient, filler, binder, wetting agent, disintegrant, absorption promoter, surfactant, adsorbent carrier, and lubricant.

5. The use of the chemokine ligand 4 antibody according to claim 1 in the preparation of a drug for treating silicosis, characterized in that: The drug may be an injectable or non-injectable formulation.

6. The use of the chemokine ligand 4 antibody according to claim 5 in the preparation of a medicament for treating silicosis, characterized in that: The dosage of the injection is 1.2 μg / 100 μL.

7. The use of the chemokine ligand 4 antibody according to claim 5 in the preparation of a medicament for treating silicosis, characterized in that: The injection is administered via tail vein injection, once a week for a total of 4 weeks.

8. The use of the chemokine ligand 4 antibody according to claim 1 in the preparation of a medicament for treating silicosis, characterized in that: The drug is in the form of tablets, capsules, powders, pills, granules, solutions, suspensions, syrups, injections, suppositories, adsorbents, or sprays.

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