CN113713103A - Application of miR-124-3p agonist in preparation of IL4R alpha protein expression inhibitor - Google Patents
Application of miR-124-3p agonist in preparation of IL4R alpha protein expression inhibitor Download PDFInfo
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Abstract
The invention discloses application of a miR-124-3p agonist in preparation of an IL4R alpha protein expression inhibitor. The miR-124-3p agonist provided by the scheme of the invention can obviously inhibit protein expression of IL4R alpha, and simultaneously reduces protein expression levels of IL4 and IL13, and has important significance for treating allergic rhinitis.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a miR-124-3p agonist in preparation of an IL4R alpha protein expression inhibitor.
Background
Human interleukin 4(IL4, IL-4), also known as BCGF-1, BCGF1, BSF-1, BSF1, and the like, is mainly produced by activated T cells, participates in humoral immunity and adaptive immunity, and is a cytokine that induces primary helper T cells to differentiate into Th2 cells. The human IL-4 gene maps to 5q31.1 and consists of 4 exons and 3 introns, approximately 10 kb. Mature human IL-4 molecules consist of 129 amino acid residues, have a molecular weight of 15kDa and contain 2 glycosylation sites. All biological functions of IL-4 are mediated by the interleukin 4 receptor (IL-4R) on the surface of effector cells, IL4R is composed of a and γ subunits, and IL-4R signal by binding to the IL-4R α chain. Human IL-4R alpha is located in 16p12.1 region, and the gene and its polymorphism are related to asthma and allergic dermatitis.
The clinical indications of the antibody drugs developed against IL-4R alpha are mainly allergy, atopic dermatitis, asthma, cancer and the like. However, some patients still do not achieve good therapeutic effects with the existing drugs. Therefore, it is of great interest to explore more effective treatments.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art described above. Therefore, the invention provides application of the miR-124-3p agonist in preparation of an IL4R alpha protein expression inhibitor.
The invention also provides an application of the IL4R alpha protein expression inhibitor.
According to one aspect of the invention, the application of the miR-124-3p agonist in the preparation of the IL4R alpha protein expression inhibitor is provided.
According to some embodiments of the invention, the raw material for preparing the inhibitor of IL4R α protein expression further comprises a pharmaceutically acceptable carrier.
According to some embodiments of the invention, the pharmaceutically acceptable carrier is a pharmaceutical carrier conventional in the pharmaceutical art.
According to some embodiments of the invention, the pharmaceutically acceptable carrier comprises at least one of a diluent, an excipient, a filler, a binder, a disintegrant, an absorption enhancer, a surfactant, an adsorptive carrier, a lubricant, a sweetener, and a flavoring agent.
According to some embodiments of the invention, the excipient comprises water.
According to some embodiments of the invention, the filler comprises at least one of starch and sucrose.
According to some embodiments of the invention, the binding agent comprises at least one of a cellulose derivative, alginate, gelatin and polyvinylpyrrolidone.
According to some embodiments of the invention, the humectant comprises glycerin.
According to some embodiments of the invention, the disintegrant comprises at least one of agar, calcium carbonate and sodium bicarbonate.
According to some embodiments of the invention, the absorption enhancer comprises a quaternary ammonium compound.
According to some embodiments of the invention, the surfactant comprises cetyl alcohol.
According to some embodiments of the invention, the adsorbent carrier comprises at least one of kaolin and bentonite.
According to some embodiments of the invention, the lubricant comprises at least one of talc, calcium stearate, magnesium stearate and polyethylene glycol.
According to some embodiments of the invention, the miR-124-3p agonist is present in the inhibitor of IL4R α protein expression in an amount of 0.1% to 99% by weight.
According to some preferred embodiments of the invention, the mass fraction of the miR-124-3p agonist in the inhibitor of expression of IL4R alpha protein is between 0.5% and 95%.
According to some preferred embodiments of the invention, the mass fraction of the miR-124-3p agonist in the inhibitor of expression of IL4R alpha protein is between 10% and 20%.
According to some embodiments of the invention, the inhibitor of IL4R α protein expression is administered in amounts that are measured by: the miR-124-3p agonist is 0.01 mg/day to 1000 mg/day.
According to some embodiments of the present invention, the dosage form of the inhibitor of IL4R α protein expression is various dosage forms conventional in the art, preferably in solid, semi-solid or liquid form, and may be an aqueous solution, a non-aqueous solution or a suspension, more preferably a tablet, a capsule, a soft capsule, a granule, a pill, an oral liquid, a dry suspension, a drop pill, a dry extract, an injection or an infusion.
According to some embodiments of the present invention, the administration of the inhibitor of IL4R α protein expression may be conventional in the art, including but not limited to injection or oral administration. The injection can be intravenous injection, intramuscular injection, intraperitoneal injection, intradermal injection or subcutaneous injection.
The term "administered dose" as used herein is an amount capable of alleviating or delaying the progression of a disease, degenerative or injurious condition. Depending on the particular disease being treated, as well as other factors including age, weight, health, severity of symptoms, route of administration, frequency of treatment, and whether other medications are concomitant during treatment.
According to another aspect of the invention, the application of the IL4R alpha protein expression inhibitor is provided, and the application is the application in the preparation of medicines for treating the strain rhinitis.
In some embodiments of the invention, the use is in the preparation of an inhibitor of IL4 protein expression.
In some embodiments of the invention, the use is in the preparation of an inhibitor of IL13 protein expression.
In some embodiments of the invention, the use is in the preparation of an inhibitor of IL5 protein expression.
In some embodiments of the invention, the use is in the manufacture of a medicament for inhibiting an increase in eosinophil number.
In some embodiments of the invention, the use is in the preparation of an inhibitor of IgE protein expression.
The application of the embodiment of the invention has at least the following beneficial effects: the miR-124-3p agonist provided by the scheme of the invention can obviously inhibit protein expression of IL4R alpha, inhibit increase of eosinophil number, reduce protein expression levels of IL4, IL13, IL5 and IgE, achieve good effect in treating allergic rhinitis, and has important significance in treating allergic rhinitis.
Drawings
The invention is further described with reference to the following figures and examples, in which:
FIG. 1 is a flow chart of the modeling of mice with allergic rhinitis in example 1 of the present invention;
FIG. 2 is a graph showing the effect of miR-124-3P agonist in example 2 on the number of sneezes in allergic rhinitis mice, wherein C is saline control group, T is miR-124-3P agonist treatment group, AR is dust mite-sensitized allergic rhinitis group, and P is < 0.05;
FIG. 3 is a graph showing the effect of miR-124-3P agonist in example 3 on the expression level of dust mite-specific IgE in serum of mice with allergic rhinitis, wherein C is saline control group, T is miR-124-3P agonist treatment group, AR is dust mite-sensitized allergic rhinitis group, and P is less than 0.05;
fig. 4 is a graph showing the effect of the miR-124-3P agonist in example 4 of the present invention on eosinophil infiltration in the nasal mucosa of allergic rhinitis mice, wherein C is saline control group, T is miR-124-3P agonist-treated group, AR is dust mite-sensitized allergic rhinitis group, P is < 0.01, and P is < 0.001;
fig. 5 is a graph showing the effect of miR-124-3P agonist on the expression level of IL4R α in nasal mucosa of mice with allergic rhinitis in example 5 of the present invention, wherein C is saline control group, T is miR-124-3P agonist-treated group, AR is dust mite-sensitized allergic rhinitis group, and P < 0.001;
fig. 6 is a graph showing the effect of miR-124-3P agonists on the expression level of IL4 in the nasal mucosa of mice with allergic rhinitis in example 5 of the present invention, wherein C is saline control group, T is miR-124-3P agonist-treated group, AR is dust mite-sensitized allergic rhinitis group, P is < 0.01, and P is < 0.001;
FIG. 7 is a graph showing the effect of the miR-124-3P agonist in example 6 on the expression level of IL4R a in the spleen of mice with allergic rhinitis, wherein NC is a control group, mimic is a miR-124-3P mimetic-treated group, and P is < 0.01;
FIG. 8 is a graph showing the effect of miR-124-3P agonist in example 6 of the present invention on the expression level of IL4 in spleen of mice with allergic rhinitis, wherein NC is a control group, mimic is a miR-124-3P mimetic-treated group, and P is < 0.05;
FIG. 9 is a graph showing the effect of the miR-124-3P agonist in example 6 of the present invention on the expression level of IL13 in the spleen of mice with allergic rhinitis, wherein NC is a control group, mimic is a miR-124-3P mimetic-treated group, and P is < 0.01;
FIG. 10 is a graph showing the effect of miR-124-3P agonist in example 6 of the present invention on IL5 protein expression in spleen, wherein NC is a control group, mimic is a miR-124-3P mimetic-treated group, and P is < 0.01.
Detailed Description
The concept and technical effects of the present invention will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present invention. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and those skilled in the art can obtain other embodiments without inventive effort based on the embodiments of the present invention, and all embodiments are within the protection scope of the present invention.
Relevant studies indicate that miRNA can target and regulate inflammatory response. According to the scheme, the whole genome comparison analysis of the allergic rhinitis mouse and the normal mouse shows that the expression of miR-124-3p in the nasal mucosa of the allergic rhinitis mouse is obviously lower than that of the normal mouse, and the miR-124-3p can be combined with IL4R alpha to negatively regulate the expression of IL4R alpha. In addition, IL4R α is the IL4 and IL13 receptor genes, the latter being key molecules in type 2 inflammatory responses.
The miR-124-3p agonist and miR-124-3p mimic (mimics) used in the invention are purchased from Ruibo Biotechnology, Inc., Guangzhou.
Example 1 allergic rhinitis mouse modeling
Experimental animals: taking C57BL/6J female mice 6-8 weeks old, randomly dividing into 3 groups, wherein each group comprises 5 mice, the group C is a normal saline control group, the group AR is a dust mite-sensitized allergic rhinitis group, and the group T is a miR-124-3p agonist treatment group.
AR modeling: it is divided into two stages of abdominal cavity sensitization and nasal cavity excitation. An abdominal cavity sensitization stage: 40 μ g HDM (Stallengenesgreener, US) was dissolved in 200 μ L physiological saline and intraperitoneally injected into the mice on days 1, 5, 10, and 15, respectively. A nose excitation stage: day 16-25 for 10 consecutive days, with nasal drip challenge of 20 μ g HDM dissolved in 20 μ L saline daily, 10 μ L nasal cavity on each side.
The difference between mice in group T and mice modeled on AR in the miR-124-3p agonist treatment group is that 1.4nmol of miR-124-3p agonist is respectively given for nasal drip intervention 3h before each nasal cavity excitation of HDM, and each nasal cavity is 10 mu L for 7 consecutive days.
Saline control group C mice were different from AR modeled mice in that they were each replaced with saline nasal drip sham. The allergic rhinitis mouse modeling flow chart is shown in figure 1.
Example 2 application of miR-124-3p agonist in alleviating nasal symptoms of allergic rhinitis mice
In 3 groups of mice prepared in example 1, the number of sneezes was observed within 15 minutes after the last nasal drip.
The experimental result is shown in figure 2, and it can be seen from the figure that the miR-124-3p agonist can effectively relieve nasal symptoms of the allergic rhinitis mice, and after the treatment by the miR-124-3p agonist, the nasal symptoms of the allergic rhinitis mice can basically reach the level of normal mice.
Example 3miR-124-3p agonists inhibit the level of dust mite-specific IgE in serum of mice with allergic rhinitis
The 3 groups of mice prepared in example 1 were bled from the eyes and the resulting serum was centrifuged to detect the level of dust mite-specific IgE using an ELISA kit (Invitrogen).
The experimental result is shown in figure 3, and it can be seen from the figure that the miR-124-3p agonist can effectively reduce the expression level of the dust mite specific IgE protein, and after the treatment by the miR-124-3p agonist, the expression level of the dust mite specific IgE protein of the allergic rhinitis mice can basically reach the level of the control group normal mice.
Example 4 Effect of miR-124-3p agonists on eosinophil infiltration in nasal mucosa of allergic rhinitis mice
The complete nasal mucosa of 3 groups of mice prepared in example 1 was dissected and separated under a microscope, immersed in 4% paraformaldehyde, treated at 4 ℃ for 12 hours, decalcified with EDTA, embedded in paraffin, sectioned, HE-stained, and the number of eosinophil infiltrations was observed under a microscope. The specific process comprises the following steps:
(1) tissue fixation and decalcification: fixing in 4% paraformaldehyde overnight at 4 deg.C, adding 10% EDTA, placing on a shaking table, decalcifying at room temperature for 3 days, and changing the liquid once a day.
(2) Gradient dehydration: 75% alcohol for 30min → 95% alcohol for 2h → absolute ethanol I for 2h → absolute ethanol II for 2 h.
(3) And (3) xylene transparency: xylene I15 min → xylene II 15 min.
(4) Wax dipping: the tissue was immersed in paraffin wax at 60 ℃ for 2h to allow the tissue to soak into the melted wax mass.
(5) Slicing: slicing with a paraffin slicer, baking at 45 deg.C for 2 hr, and dyeing.
(6) Dewaxing: xylene I15 min → xylene II 15 min.
(7) Gradient rehydration: absolute ethyl alcohol I10 min → absolute ethyl alcohol II 10min → 95% alcohol 5min → 75% alcohol 5min → double distilled water 1 min.
(8) Hematoxylin-eosin staining: staining with hematoxylin water solution for 5min, and flushing with running water for 5 min. 1% ethanol hydrochloride (75% ethanol +5ml hydrochloric acid) removed the color of the components other than the cell nucleus and left for 2 seconds. And flushing with flowing water for 2 minutes, flushing with hydrochloric acid, and flushing with double distilled water for 2 minutes. Then the obtained product is placed into alcohol eosin dye liquor for dyeing for 5 minutes, and is washed by double-distilled water for 2 seconds.
(9) And (3) dehydrating: 1min of 75% alcohol → 5min of 95% alcohol → 5min of absolute ethyl alcohol II.
(10) And (3) xylene transparency: xylene I5 min → xylene II 5 min.
(11) And sealing the neutral gum, naturally drying the slices, and observing under a microscope.
The experimental results are shown in FIG. 4, and it can be seen that the miR-124-3p agonist can effectively reduce the number of eosinophils.
Example 5 Effect of miR-124-3p agonists on the number of IL4R α, IL4 positive cells in the nasal mucosa of allergic rhinitis mice
Dissecting and separating intact nasal mucosa under microscope, soaking in 4% paraformaldehyde, performing EDTA decalcification after overnight refrigeration at 4 deg.C, embedding in paraffin, slicing, performing immunofluorescence staining on IL4R alpha, observing the number of IL4R alpha positive cells under the microscope, performing immunohistochemical staining on IL4, and observing the number of IL4 positive cells under the microscope. The experimental method comprises the following steps:
1. immunofluorescence detection of mouse nasal mucosa IL-4R alpha expression
(1) Dewaxing: xylene I15 min → xylene II 15min → absolute alcohol I5 min → absolute alcohol II 5min → 85% alcohol 5min → 75% alcohol 5min → double distilled water wash.
(2) Repairing antigen: putting the EDTA antigen repairing solution into a microwave oven for repairing.
(3) Quenching: the tissue was circled with a histochemical pen, quencher was added and after 5 minutes rinsed with water.
(4) Blocking, BSA was added to the loop and incubated for 30 min.
(5) Adding a primary antibody: the blocking solution was spun off, washed with PBS and incubated overnight at 4 ℃ in a chamber containing primary antibody.
(6) Adding a secondary antibody: PBS was washed 3 times for 5 minutes each. Spin-drying the slices, adding secondary antibody dropwise, and incubating for 50min in dark.
(7) Counterstaining nuclei: PBS was washed 3 times for 5 minutes each. DAPI stain was added and incubated for 10min in the dark.
(8) Sealing: PBS was washed 3 times for 5 minutes each. Mounting the plate with an anti-fluorescence quencher.
(9) And (3) photographing: observed under a fluorescent microscope and photographed.
2. Immunohistochemical detection of mouse nasal mucosal IL-4 expression
(1) Dewaxing: xylene I15 min → xylene II 15min → xylene III 15min → absolute alcohol I5 min → absolute alcohol II 5min → 85% alcohol 5min → 75% alcohol 5min → double distilled water wash.
(2) Repairing antigen: and (3) placing the tissue slices into a box containing citric acid antigen repairing liquid, and placing the box into a microwave oven for repairing the antigen.
(3) Blocking endogenous peroxidase: put into 3% hydrogen peroxide solution, incubate for 25 minutes in the dark, wash 3 times with PBS for 5 minutes each.
(4) And (3) sealing: 3% BSA was added dropwise to the assembly circle, and the assembly was blocked at room temperature for 30 minutes.
(5) Adding a primary antibody: the blocking solution was gently spun off, washed with PBS and incubated overnight at 4 ℃ in a chamber containing primary antibody.
(6) Adding a secondary antibody: PBS was washed 3 times for 5 minutes each. The secondary antibody was added dropwise to the circle and incubated for 50 minutes in the dark.
(7) Color development: PBS was washed 3 times for 5 minutes each. DAB color developing solution is dripped into the ring, and the section is washed by running water to stop color development.
(8) Counterstaining nuclei: hematoxylin was added and rinsed with water after 3 minutes. Hematoxylin differentiation solution was then added and after a few seconds, rinsed with water. Finally adding hematoxylin bluing liquid and washing with water.
(9) Sealing: 75% alcohol 5min → 85% alcohol 5min → absolute alcohol I5 min → absolute alcohol II 5min → xylene I5 min, air dried and then encapsulated with neutral gum.
The experimental result is shown in fig. 5-6, and as can be seen from fig. 5, the miR-124-3p agonist can significantly reduce the expression level of IL4R alpha in nasal mucosa of mice with allergic rhinitis, and can basically reach the level of normal mice in a control group; as can be seen from FIG. 6, the miR-124-3p agonist can significantly reduce the expression level of IL4 in nasal mucosa of mice with allergic rhinitis
Example 6 Effect of miR-124-3p mimic on expression levels of IL4R α, IL4, IL15 and IL13 in spleen
The strain rhinitis mice prepared in example 1 are removed from spleen, lymphocytes are separated, miR-124-3p mimics are transfected to stimulate miR-124-3p, and RT-qPCR is used for detecting the mRNA expression levels of IL4R alpha, IL4, IL5 and IL 13. The method comprises the following steps:
1. extraction of mouse spleen lymphocytes
(1) Spleens of mice were aseptically harvested and the splenic capsule was removed.
(2) The filter was placed in a 50ml centrifuge tube and wetted with tissue diluent.
(3) The spleen was placed on a filter screen, ground with a syringe plunger, and the washed cells were collected.
(4) To the collected single cell suspension, an equal lymphocyte separation medium was added.
(5) The single cell suspension was aspirated and added to the surface of the separation medium.
(6) After centrifugation, the cells were separated into four layers from top to bottom. The first layer is a diluent; the second layer is opalescent lymphocytes; the third layer is transparent separation liquid; the fourth layer is red blood cells.
(7) Pipette the lymphocyte cell layer into a new 15mL centrifuge tube, add 10mL of wash solution, 300 Xg, and centrifuge for 10 min.
(8) The supernatant was discarded, 5mL of PBS was used to resuspend the cells, 300 Xg, and centrifuged for 5 min.
(9) The supernatant was discarded and the cells were resuspended for use.
2. miR-124-3p mimic transfected cell
(1) Cell preparation cells were seeded in 24-well plates 1 day before transfection, and the number of seeded cells was determined according to the cell growth rate and cell line type, and was generally 0.5 to 1X 106 cells. The medium was replaced with fresh medium 2 hours before transfection.
(2) Mu.l Lipofectamine 3000 reagent (ThermoFisher, US) was added to 25. mu.l Opti-MEM medium, mixed gently, and allowed to stand at room temperature for 2-3 minutes.
(3) And respectively adding 2.5 mu L of miR-124-3p micnc and 2.5 mu L of miR-124-3p micnc into 50 mu L of Opti-MEM reduced serum culture medium for dilution to prepare a premixed solution.
(4) And respectively adding the diluted miR-124-3p micnc and miR-124-3p micnc into the diluted Lipofectamine 3000 reagent, and incubating for 10-15 minutes.
(5) The above mixture was added dropwise to 24-well plates, 0.5. mu.L of IL-2, 0.25. mu.L of CD3 antibody and 0.25. mu.L of CD28 antibody were added to each well, and finally Opti-MEM reduced serum medium was added to 500. mu.L each well, which was shaken well and then added to 37 ℃ CO2Culturing in an incubator.
(6) After 23 hours, 2.5. mu.L of HDM (1. mu.g/. mu.L) was added to each well of cells for 1 hour of in vitro stimulation, and then the cells were collected and the expression of the relevant genes and proteins was detected by RT-qPCR.
3、
Total RNA Kit II for extracting Total RNA of mouse spleen cells
(1) Spleen lymphocytes in 24-well plates were collected: the cells in each well were washed with physiological saline, and centrifuged to obtain a cell pellet.
(2) Adding 1ml of RNA lysate to lyse cells, transferring the liquid to a 1.5ml centrifuge tube, and standing at room temperature for 5 min.
(3) Adding 200 μ L chloroform, shaking at high speed for 20s, and standing at room temperature for 2 min.
(4) Centrifugation was carried out at 12000 Xg for 15min at 4 ℃.
(5) Transfer the supernatant to a 2ml centrifuge tube and add equal 70% ethanol.
(6) The RNA binding column was inserted into the collection tube, the liquid from the previous step was added, centrifuged at 10000 Xg for 1min at room temperature, and the filtrate was discarded.
(7) Repeating step (6) until all the liquid is bound to the RNA binding column.
(8) The RNA binding column was inserted into the collection tube, 500. mu.L of RNA Wash Buffer I was added, and the mixture was centrifuged at 10000 Xg for 30s, and the filtrate was discarded.
(9) The RNA binding column was inserted into the collection tube, 500. mu.L of RNA Wash buffer II was added, centrifugation was carried out at 10000 Xg for 1min, and the filtrate was discarded.
(10) And (5) repeating the step (9).
(11) The RNA binding column was inserted into the collection tube and spun off at 10000 Xg for 2 min.
(12) The RNA binding column was inserted into a new 1.5ml centrifuge tube, appropriate amount of DEPC water was added, and centrifugation was carried out for 2min at 10000 Xg.
(13) Finally, the RNA concentration is measured. The OD260/280 values between 1.8 and 2.0 are generally considered to be very pure.
Reverse transcription of Total RNA into cDNA
(1) RNA denaturation: heat denatured at 65 ℃ for 5min and immediately cooled on ice.
(3) Removal of genomic DNA: the reaction solution was prepared on ice.
(4) Reverse transcription: the reaction solution was prepared on ice. After the reaction solution is mixed evenly, the reaction is carried out according to the following temperature and time: 37 ℃/15min → 50 ℃/5min → 98 ℃/5min → 4 ℃. The cDNA was stored at-20 ℃.
4. RT-qPCR detection of mRNA expression levels of IL-4R alpha, IL-4, IL-5 and IL-13 of mouse spleen lymphocytes
TABLE 1
(1) The cDNA obtained by reverse transcription is taken as a template, PCR reaction liquid is prepared on ice according to the following components, and recording is made. The fluorescent quantitative PCR primers for IL-4R α, IL-4, IL-5 and IL-13 genes are shown in Table 1.
(2) After the sample is added, the top of the cover is not touched, the cover is covered, the mixture is fully mixed, and the mixture is centrifuged on a small centrifuge for a few seconds to prepare for loading.
(3) Performing RT-qPCR detection by using a Roche LightCycler 480 real-time fluorescent quantitative PCR system, and setting an RT-qPCR instrument: firstly, the reaction temperature is 95 ℃, the time is 30s, and the cycle number is 1; the reaction temperature is 95 ℃, the reaction time is 5s, the reaction temperature is 60 ℃, the reaction time is 30s, and the cycle number is 40; ③ the reaction temperature is 95 ℃, the time is 5s, the reaction temperature is 60 ℃, the time is 1min, and the cycle number is 1; fourthly, the reaction temperature is 50 ℃, the time is 30s, and the cycle number is 1. The well plate was placed in an RT-qPCR apparatus for amplification. And (3) deriving CT values after the detection is finished, making 3 repeated holes on each sample, calculating the average value of the samples, and calculating the relative content of the target mRNA by using a formula 2-delta Ct. The internal reference gene was β -actin, and primers were designed using PrimerBank and synthesized by Sangon Biotech, Inc., Productivity Co.
The experimental results are shown in FIGS. 7-10, and it can be seen from the graphs that the mRNA expression levels of IL4R alpha, IL4, IL5 and IL13 in the spleen of the strain rhinitis mice can be effectively reduced by using the miR-124-3p agonist.
Allergic rhinitis is a non-infectious chronic inflammatory disease of the nasal mucosa mediated primarily by IgE after exposure of the body to allergens. The global incidence rate is about 10-40%, and the trend is rising. Symptoms such as nasal obstruction, watery nasal discharge, sneeze and even headache frequently occur during the allergic rhinitis attack, which seriously affect the sleep, work, study and memory of patients and even cause emotional and cognitive disorders such as depression. Therefore, it is very important to actively control and treat the occurrence and development of allergic rhinitis.
At present, the main treatment modes of allergic rhinitis comprise allergen contact avoidance, drug therapy, immunotherapy, surgical therapy, traditional Chinese medicine therapy and other comprehensive treatments. However, a good therapeutic effect is still not obtained in some patients. The application of the protocol is therefore also of great significance for the treatment of allergic rhinitis.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present invention. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.
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Claims (9)
- Application of miR-124-3p agonist in preparation of IL4R alpha protein expression inhibitor.
- 2. The use according to claim 1, wherein the inhibitor of the expression of IL4R α protein is prepared from a starting material further comprising a pharmaceutically acceptable carrier.
- 3. The use of claim 2, wherein the pharmaceutically acceptable carrier comprises at least one of a diluent, excipient, filler, binder, disintegrant, absorption enhancer, surfactant, adsorptive carrier, lubricant, sweetener, and flavoring agent.
- 4. The use of claim 1, wherein the miR-124-3p agonist is present in the inhibitor of expression of IL4R α protein in an amount of 0.1% to 99% by weight.
- 5. The use of claim 4, wherein the mass fraction of the miR-124-3p agonist in the inhibitor of the expression of the IL4R alpha protein is 0.5-95%.
- 6. The use of claim 5, wherein the mass fraction of the miR-124-3p agonist in the inhibitor of the expression of the IL4R alpha protein is 10% -20%.
- 7. The use according to claim 1, wherein the inhibitor of IL4R α protein expression is administered in amounts measured as: the miR-124-3p agonist is 0.01 mg/day to 1000 mg/day.
- 8. The use of the inhibitor of IL4R α protein expression of claim 1 in the preparation of an inhibitor of IL4 protein expression.
- 9. Use of the inhibitor of IL4R α protein expression according to claim 1 for the preparation of an inhibitor of IL13 protein expression.
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| CN110105451A (en) * | 2018-02-01 | 2019-08-09 | 北京凯因科技股份有限公司 | IL-4R Alpha antibodies and application thereof |
| US20200208152A1 (en) * | 2017-09-08 | 2020-07-02 | Mina Therapeutics Limited | Stabilized sarna compositions and methods of use |
| US20200255827A1 (en) * | 2017-09-08 | 2020-08-13 | Mina Therapeutics Limited | Stabilized hnf4a sarna compositions and methods of use |
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|---|---|---|---|---|
| US20200208152A1 (en) * | 2017-09-08 | 2020-07-02 | Mina Therapeutics Limited | Stabilized sarna compositions and methods of use |
| US20200255827A1 (en) * | 2017-09-08 | 2020-08-13 | Mina Therapeutics Limited | Stabilized hnf4a sarna compositions and methods of use |
| CN110105451A (en) * | 2018-02-01 | 2019-08-09 | 北京凯因科技股份有限公司 | IL-4R Alpha antibodies and application thereof |
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