CN114870001A - Application of IL-33 in preparing medicine for preventing and/or treating aortic dissection - Google Patents

Abstract

The invention discloses an application of IL-33 in preparing a medicament for preventing and/or treating aortic dissection, belonging to the field of medical preparations. The technical problem to be solved by the invention is how to use the medicine to prevent and/or treat the thoracic aortic dissection. The invention provides an application of IL-33 in preparing a medicament for preventing and/or treating aortic dissection. Experiments prove that IL-33 can effectively prevent the formation and the development of aortic dissection and has the effects of preventing and treating the aortic dissection.

Description

Application of IL-33 in preparing medicine for preventing and/or treating aortic dissection

Technical Field

The invention belongs to the field of medical preparations, and particularly relates to an application of IL-33 in preparation of a medicament for preventing and/or treating aortic dissection.

Background

Aortic Dissection (AD) refers to the pathological changes of the aorta with a breach in intima or media, and blood enters the media from the breach, tears the media completely, and then expands along the major axis of the aorta to form the true and false lumens. Aortic dissection results in a series of manifestations including tear-like pain, which if not properly and timely treated, in turn leads to aortic rupture with a post-rupture mortality rate of >90%, ranking first in cardiovascular critical illness.

Various factors are involved in the onset of aortic dissection including genetic factors, hypertension, smoking, and other cardiovascular risk factors. The main pathological changes of aortic dissection are: degenerative changes of the artery intima caused by various pathological factors, including loss of smooth muscle cells, phenotypic transformation, initiation of inflammatory response, rupture and degradation of Extracellular matrix (ECM), etc., cause constant expansion and even rupture of the artery wall under the action of blood flow, etc., and the tearing of local intima can cause blood flow to rapidly enter the artery wall media to form a false cavity, resulting in formation of an arterial interlayer.

Interleukin-33 (IL-33) is a member of the IL-1 family, and is constitutively expressed in endothelial and epithelial cells at the barrier site and is induced in infiltrating inflammatory cells at the site of inflammation. As a warning agent, IL-33 can be released rapidly from damaged or necrotic cells. ST2 is the receptor for IL-33 and has two major subtypes: transmembrane (ST2L) and soluble (sST 2).

Disclosure of Invention

The technical problem to be solved by the invention is as follows: how to use drugs for prevention and/or treatment of aortic dissection.

In order to solve the above technical problems, the present invention provides, in a first aspect, an application of IL-33, which may be an application of IL-33 in the preparation of a medicament for preventing and/or treating aortic dissection.

Further, in the above application, the aortic dissection may be a thoracic aortic dissection.

Further, in the above-mentioned use, the prevention and/or treatment of aortic dissection may comprise inhibiting or reducing formation of thoracic aortic dissection.

Further, in the above application, the inhibiting or reducing of the formation of the thoracic aortic dissection may be inhibiting the formation of a thoracic aortic lesion or reducing the degree of thoracic aortic lesion.

Further, in the above-mentioned use, the prevention and/or treatment of aortic dissection may include inhibiting organ damage caused by thoracic aortic dissection.

Further, in the above applications, the inhibiting organ damage caused by thoracic aortic dissection may include reducing the extracellular volume of the heart and/or reducing the content of organ damage markers.

In one embodiment of the invention, the cardiac extracellular volume may be assessed by nuclear magnetic resonance techniques. The organ injury markers may include: cardiac injury biomarker Troponin (TNI), liver injury biomarker aspartate Aminotransferase (ALT), alanine Aminotransferase (AST), and/or kidney injury Biomarker Urea Nitrogen (BUN).

In the present invention, the IL-33 may be a natural IL-33, such as a mammalian-derived IL-33, or a non-natural IL-33, such as a recombinant IL-33, and the recombinant IL-33 may have the function of a natural IL-33.

Further, in the above-mentioned application, the IL-33 may be a recombinant human IL-33.

Further, in the above applications, the amino acid sequence of the recombinant human IL-33 in NCBI has the following reference sequence: NP-254274.1 (Update Date JUL 03,2022).

In one embodiment of the present invention, the recombinant human IL-33 is purchased from Beijing Yi Qian Shen science and technology, Inc., under the following product number: 10368-HNAE.

Further, in the above application, the drug for preventing and/or treating aortic dissection can be a drug administered through gastrointestinal tract, a drug administered through intravenous injection, or a drug administered by a subcutaneous embedding administration mode.

In the medicament for preventing and/or treating aortic dissection, recombinant human IL-33 can be used as one of the effective components.

In the present invention, when preparing a medicament for preventing or treating aortic dissection, a carrier material may also be added.

The carrier material includes, but is not limited to, water-soluble carrier materials (e.g., polyethylene glycol, polyvinylpyrrolidone, organic acids, etc.), sparingly soluble carrier materials (e.g., ethyl cellulose, cholesterol stearate, etc.), enteric carrier materials (e.g., cellulose acetate phthalate, carboxymethyl cellulose, etc.). The materials can be prepared into various dosage forms, including but not limited to tablets, capsules, dripping pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, liposomes, transdermal agents, buccal tablets, suppositories, freeze-dried powder injections and the like. Can be common preparation, sustained release preparation, controlled release preparation and various microparticle drug delivery systems. In order to prepare the unit dosage form into tablets, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agents such as dried starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene, sorbitol fatty acid ester, sodium dodecylsulfate, methyl cellulose, ethyl cellulose, etc.; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao butter, hydrogenated oil and the like; absorption accelerators such as quaternary ammonium salts, sodium lauryl sulfate and the like; lubricants, for example, talc, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer and multi-layer tablets. In order to prepare the dosage form for unit administration into a pill, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, kaolin, talc and the like; binders such as acacia, tragacanth, gelatin, ethanol, honey, liquid sugar, rice paste or batter, etc.; disintegrating agents, such as agar powder, dried starch, alginate, sodium dodecylsulfate, methylcellulose, ethylcellulose, etc. In order to prepare the unit dosage form into suppositories, various carriers known in the art can be widely used. As examples of the carrier, there may be mentioned, for example, polyethylene glycol, lecithin, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semisynthetic glycerides and the like. In order to prepare the unit dosage form into preparations for injection, such as solutions, emulsions, lyophilized powders and suspensions, all diluents commonly used in the art, for example, water, ethanol, polyethylene glycol, 1, 3-propanediol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol fatty acid esters, etc., can be used. In addition, for the preparation of isotonic injection, sodium chloride, glucose or glycerol may be added in an appropriate amount to the preparation for injection, and conventional cosolvents, buffers, pH adjusters and the like may also be added. In addition, colorants, preservatives, flavors, flavorings, sweeteners or other materials may also be added to the pharmaceutical preparation, if desired.

The preparation can be used for subcutaneous embedding administration; administered via the digestive tract, such as orally; and the injection administration comprises subcutaneous injection, intravenous injection, intramuscular injection, intracavity injection and the like.

The invention has the following beneficial technical effects: the IL-33 provided by the invention can effectively inhibit or reduce the formation of aortic dissection and/or the damage degree of aortic dissection. Provides support of experimental data and drug selection for drug prevention and/or treatment of aortic dissection.

Drawings

FIG. 1 shows the degree of injury in the aortic dissection model.

Figure 2 is the serum soluble ST2 level in the aortic dissection model.

Figure 3 is a correlation of cardiac injury biomarker Troponin (TNI) with mouse aortic injury severity.

FIG. 4 is a graph of the correlation of the liver injury biomarker aspartate Aminotransferase (ALT) with the severity of aortic injury in mice.

FIG. 5 is a graph of the correlation of alanine Aminotransferase (AST) with the severity of aortic injury in mice.

Figure 6 is a correlation of the kidney injury Biomarker Urea Nitrogen (BUN) level with mouse aortic injury severity.

FIG. 7 is a graph showing the prophylactic effect of IL-33 administration on aortic dissection.

FIG. 8 is a FA _ CINE _ FLASH sequence fitting equation.

FIG. 9 shows the results of an experiment in which IL-33 prevents the increase in extracellular volume of heart cells caused by aortic dissection.

FIG. 10 shows the results of an experiment in which IL-33 can prevent renal injury due to aortic dissection.

FIG. 11 shows the results of an experiment in which IL-33 can prevent liver damage due to aortic dissection.

FIG. 12 shows aortic dissection and rupture rates.

FIG. 13 is a statistical result of the therapeutic effect of administration of rpIL-33 on aortic dissection.

FIG. 14 is a survival curve for aortic dissection given IL 33.

Detailed Description

The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.

The experimental procedures in the following examples, unless otherwise indicated, are conventional and are carried out according to the techniques or conditions described in the literature in the field or according to the instructions of the products. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

The following examples were processed using SPSS11.5 statistical software and the results were expressed as mean ± standard deviation using One-way ANOVA test with significant difference (P < 0.05), with very significant difference (P < 0.01), and with very significant difference (P < 0.001).

Example 1: construction and evaluation of aortic dissection mouse model (mouse TAD model)

1.1 construction method

Respectively constructing an aortic dissection mouse model by using an Ang II perfusion method, and specifically comprising the following operation steps:

ang II perfusion: 15 male BALB/c mice, 20-25g, 6-8 weeks old, were selected and purchased from Beijing Huafukang Biotech GmbH. All animals were bred in the SPF-grade environmental animal room of the institute for cardiovascular and pulmonary diseases, Beijing, Ang II (angiotensin II, Sigma, A9525) was dissolved in 0.1% acetic acid aqueous solution and was infused by an Alzet osmotic pump (1007D, Alzet) for 7 days to construct an aortic dissection mouse model at an infusion dose of 1. mu.g/kg/min.

1.2 evaluation of mouse TAD model

The evaluation scheme for the effect of the model induction interlayer is as follows: unified treatment for no death during model construction and after 7 days, and material drawing of mouse aorta. Referring to Chinese aortic dissection diagnosis and treatment guidelines, the aortic injury degree is divided into: mild injury: dissections only involve the descending aorta and its distal end; moderate damage: the dissections involve the ascending aorta, and the abdominal aorta is merged or not merged, so that the injury is discontinuous; ③ severe injury: the primary laceration is located in the ascending aorta, the injury reaches the abdominal aorta, and death occurs during continuous injury or induction model process.

Example 2: animal model verification that aorta injury degree is related to each organ injury biomarker

2.1 test methods

2.1.1 construction of animal models

An aortic dissection mouse model (15 mice) was constructed using Ang II infusion as described in example 1, and saline was infused as a control group (4 mice) in the same treatment method.

2.1.2 carotid bleeding and serum isolation

At the end of aortic dissection mouse model construction (7 days after Ang II perfusion), mice were sacrificed under anesthesia with 1% pentobarbital solution (100mg/kg, 1% pentobarbital solution usage/mouse weight), animals were fixed in elevation, neck skin was incised, subcutaneous connective tissue was separated, carotid arteries were separated on both sides of trachea to fully expose carotid arteries, cut into the cardiac end, blood was aspirated with syringe and transferred into EP tubes. Centrifuging at 3000r/min for 15min, and separating upper layer serum.

2.1.3 detection of biomarkers for injury to various organs

Serum from mice prepared at 2.1.2 was tested by ELISA for sST2 levels and for biomarkers of injury in various organs, including cardiac injury biomarker Troponin (TNI), liver injury biomarker aspartate and alanine Aminotransferases (AST) and kidney injury Biomarker Urea Nitrogen (BUN).

Taking the detection of the level of mouse serum soluble ST2(sST2) as an example, the specific detection steps are as follows:

mouse serum sST2 level was measured using Mouse ST2/IL-33R (R & D systems, MST200, USA) according to the instructions of the products, with the following steps:

1) placing all reagents and samples at room temperature before use, performing duplicate determination on all standards, controls and samples, and preparing all reagents, working standards, quality controls and samples;

2) removing the redundant microporous plate strips from the plate frame, putting the redundant microporous plate strips back into the aluminum foil bag filled with the desiccant bag, and then resealing;

3) 50 μ L of Assay dilution RD1-41 was added to each well;

4) 50 μ L of standard, control or sample was added per well. Covered with the tape provided and incubated for 2 hours at room temperature on a horizontal orbital microplate shaker set at 500 ± 50 rpm;

5) each well was aspirated and washed, and the process was repeated four times for a total of five washes; washing was performed by filling each well with a washing buffer (400 μ L) using a squirt bottle, a manifold dispenser, or an automatic washer; complete removal of liquid in each step is critical for good performance, and after the last wash any remaining wash buffer is removed by aspiration or decantation. Invert the plate and blot with clean paper towel;

6) add 100. mu.L Mouse ST2 Conjugate to each well, re-cover and incubate for 2 hours on a shaker at room temperature;

7) repeating the pumping/washing in step 5;

8) adding 100 mu L of substrate solution into each hole, and incubating for 30 minutes on a workbench at room temperature in a dark place;

9) add 100. mu.L of stop solution to each well, gently tap to ensure thorough mixing;

10) the optical density of each well was determined within 30 minutes using a microplate reader set at 450 nm.

Detecting the content of cardiac injury biomarker Troponin (TNI) in mouse serum by using a mouse cardiac Troponin (TNI) kit (GeneMei, cat number JYM0409Mo) according to a product instruction;

detecting the content of alanine Aminotransferase (ALT) in the serum of the mouse by using an ALT (alanine aminotransferase assay kit) (Radu, cargo number S03030) according to a product instruction;

detecting the content of aspartate Aminotransferase (AST) in the serum of the mouse by using an aspartate aminotransferase AST (Radu, cargo number S03040) detection kit according to a product specification;

the content of urea nitrogen (BUN) in mouse serum was determined using a urea nitrogen assay kit (ledum, cat # S03036) according to the product instructions.

2.2, results of the experiment

2.1 constructing aorta interlayer mouse model to obtain 5 mice with mild injury, 1 mouse with moderate injury and 3 mice with severe injury.

The results of the mouse dissection photographs and the injury marker measurements are shown in FIGS. 1 to 6.

FIG. 1 shows the degree of injury in the aortic dissection model. 4 models of the damage degree are shown respectively: control group perfused with normal saline, mild injury (interlayer only affects descending aorta), moderate injury (interlayer affects ascending aorta), and severe injury (primary laceration is located in ascending aorta, injury reaches abdominal aorta, and injury is continuous);

FIG. 2 is the serum soluble ST2(sST2) level in the aortic dissection model. The ordinate of figure 2 is the logarithm of the base 10 serum sST2 levels, and the abscissa is the mouse serum with different degrees of aortic injury. The results show that: the increase in the level of sST2 positively correlated with the severity of aortic injury in mice (Pearson correlation coefficient 0.963, P < 0.001).

Fig. 3 is a correlation of cardiac injury biomarker Troponin (TNI) with mouse aortic injury severity, fig. 4 is a correlation of liver injury biomarker aspartate Aminotransferase (ALT) with mouse aortic injury severity, fig. 5 is a correlation of alanine Aminotransferase (AST) with mouse aortic injury severity, and fig. 6 is a correlation of kidney injury Biomarker Urea Nitrogen (BUN) level with mouse aortic injury severity. The results show that the level of circulating soluble ST2 in mice is positively correlated with the level of organ damage (Pearson correlation coefficient for sST2 with Troponin (TNI) 0.575, P = 0.0064; Pearson correlation coefficient for aspartate Aminotransferase (ALT) 0.797, P = 0.0002; Pearson correlation coefficient for alanine Aminotransferase (AST) 0.699, P = 0.0026; Pearson correlation coefficient for urea nitrogen (BUN) 0.627, P = 0.0218). The base of the logarithm in the ordinate in fig. 3-6 is 10.

Example 3: prophylactic effects of IL33 administration on aortic dissection

3.1 Experimental procedures

3.1.1 recombinant human IL-33 protein

The recombinant human IL-33 protein (rpIL-33) was purchased from Beijing Yiqiao Shenzhou science and technology GmbH, having the following product number: 10368-HNAE.

The amino acid sequence of the recombinant human IL-33 protein at NCBI has the reference sequence numbers: NP-254274.1 (Update Date JUL 03,2022).

3.1.2 test methods

35 male BALB/c mice, 20-25g, 6-8 weeks old, were selected and purchased from Beijing Huafukang Biotech GmbH. All animals were bred in the SPF-level environmental animal house of the institute of cardiovascular and cerebrovascular diseases, Beijing. 35 male BALB/c mice, 20-25g, 6-8 weeks old, were randomized into three groups: IL33 prevention group (AngII + IL-33), model group (AngII) and control group (saline), the number of mice per group was 15, 5 respectively.

IL-33 prevention group (AngII + IL-33): each mouse was infused daily with Ang II solution (solvent 0.1% acetic acid in water and solute Ang II (Sigma, A9525) by an Alzet osmotic pump (1007D, Alzet), continuously for 7 days at an infusion dose of 1. mu.g/kg/min, and each mouse was administered with rpIL-33 solution (solvent physiological saline and solute rpIL-33) at a dose of 0.2. mu.g rpIL-33/g (mouse body weight)/day by injecting the rpIL-33 solution once in the cavity on days 1,3, 5 and 7 from the start of the infusion of the Ang II solution, respectively.

Model group (Ang II): each mouse was infused daily with Ang II solution (solvent 0.1% aqueous acetic acid, solute Ang II (Sigma, A9525)) via an Alzet osmotic pump (1007D, Alzet) at a dose of 1. mu.g/kg/min for 7 consecutive days, with 100. mu.l per mouse per injection per day, by intraluminal injection of physiological saline on days 1,3, 5 and 7 from the start of the infusion of Ang II solution.

Control group (saline): the Alzet osmotic pump infuses the same amount of physiological saline as the model group, and intraperitoneally injects physiological saline 100 μ l each per mouse on days 1,3, 5, and 7 from the start of the infusion of Ang II solution.

3.1.3, uniformly treating the mouse aorta without death in the model construction process and after 7 days, taking materials from the aorta of the mouse according to the steps of the embodiment 1.2, and counting the damage degree of the aorta.

3.2, results of the experiment

The prophylactic effect of IL33 administration on aortic dissection is shown in Table 1 and figure 7.

Table 1: model construction results of aortic dissection given IL33

Experiment grouping	Without damage	Mild injury	Moderate injury	Severe injury	Death by accident
						Model set	4 are	5 are	1 is composed of	3 pieces of	2 are
IL-33 preventive group	8 are	4 are	1 is composed of	1 is composed of	1 is composed of

The total number of mice dead due to mild injury, toxic injury, severe injury and aortic injury is used as the number of models, the number of mice dead due to no injury is used as the number of non-models, and the mice dead due to other reasons except for model building are not included in statistics.

The results of table 1 and fig. 7 show that: the overall modulus of the IL-33 prevention group is significantly lower than that of the model group, and particularly the number of models with severe injury is significantly lower than that of the model group; this result demonstrates that the rpIL-33 intervention significantly reduced the incidence of aortic dissection (42.9% vs69.2%), especially severe aortic injury (7.1% vs 23.1%).

Example 4: administration of IL-33 to ameliorate multiple organ injury due to aortic dissection

4.1 Experimental procedures

4.1.1 mouse model constructed using example 3

4.1.2, evaluating the perfusion condition of the heart, the liver and the kidney of the mouse by the nuclear magnetism of the small animal one day before the material is obtained. The method comprises the following specific steps:

1) the abdominal cavity of 250ul avermectin is used for anesthesia, after an osmotic pump is taken out, subcutaneous copper needle electrocardio electrodes are inserted into the left forelimb and the two side hind limbs of the mouse, the mixed gas of high-purity oxygen and isoflurane (1% -2%) is input during MRI scanning, and a rodent respiratory mask is used for maintaining the respiratory frequency at 40-50 times/min.

2) An ECG module (Model 1030, SA Instruments inc., usa) was used to acquire respiratory and cardiac electrical signals and trigger cardiac and respiratory gating.

3) CINE imaging of the mid-left ventricle and apical portion of the short axial axis of the heart was performed using the 5FA _ CINE _ FLASH and 3FA _ CINE _ FLASH sequences.

4) Baseline images were acquired followed by an automatic injection of 0.37g/ml 40 ul/mic Gadolinium contrast agent (Gadolinium) over 4-5s via the angular vein and further acquisition for a total time of up to 12 min.

5) The T1 values for the left ventricular wall were calculated using the curve fitting kit of Matlab2010 (Mathworks inc., usa). The FA _ CINE _ FLASH sequence fitting formula is shown in fig. 8, where in fig. 8 SI is the acquired imaging signal intensity, T1 is the inversion time, TR is the repetition time, TE is the echo time, and α is the flip angle.

6) Curve fitting was performed using the Levenberg-Marquardt algorithm to calculate M0, T1 values, T2 values.

And judging the curve fitting degree by determining a coefficient and an error square.

7) Calculation of left ventricular wall T1 values myocardial activity and lesion extent were studied by examining changes in myocardial T1 values by first manually plotting the endocardial and epicardial contours of the mice. Myocardial primitive T1 values (pre.t1) and blood pool Tl values were measured, post-dose myocardial T1 values [ T1(T) -myo ] and blood pool Tl values [ T1(T) -blood ], and extracellular volume fraction (ECV) was calculated in conjunction with HcT.

4.1.3 Kidney and liver T2 assays

The liver and kidney positions were determined using the T1 sequence, and then the lesion positions were determined using the SWI sequence. Scans using the T2 mapping sequence covered the entire kidney and liver. Renal and hepatic T2 values were measured using Mricron software. The influences of the intervention of the rpIL-33 on organ perfusion failure and injury, the prognosis of the rpIL-33, and the evaluation of the perfusion failure condition of each organ by magnetic resonance imaging are shown, compared with a control group of mice, the ECV value of the myocardium of a model group of mice is obviously increased, which indicates that serious myocardial injury and edema exist, and compared with the model group, the extracellular volume of the heart cell of an IL-33 prevention group is obviously reduced (P is less than 0.0001, and figure 9); the IL-33 prevented group had significantly elevated renal T2 values compared to the model group (P < 001, fig. 10); the IL-33-prevented group had significantly higher liver T2 values compared to the model group (P < 0001, fig. 11); these results indicate that IL33 administration ameliorated multi-organ injury due to aortic dissection.

Example 5: therapeutic Effect of IL33 administration on aortic dissection

5.1 Experimental procedures

5.1.1 model construction

BAPN water feeding method: a rat aortic dissection mouse model was constructed by taking A3-week-old male mouse with a C57BL/6 background and weighing about 10g, and administering a normal diet, dissolving BAPN (3-aminopropionitrile fumarate, Sigma, A3134) in drinking water at a dose of 1g/kg/day, and feeding the mouse for 4 weeks. C57BL/6 background Male mice were purchased from Beijing Weishanglide Biotech, Inc.

All animals were bred in the SPF-level environmental animal house of the institute of cardiovascular and cerebrovascular diseases, Beijing.

5.1.2 mice with 5.1.1 induced aortic dissection were randomized into three groups, one group being the IL-33 treatment group (18): from the 14 th day of BAPN-containing water feeding, performing intraperitoneal injection of rpIL-33 once every two days at the dose of 2 mug/ml and 100 ul/mouse; the other group was a control group (10): the same frequency as in the IL-33 treatment group, differing only by: the same volume of saline was given by intraperitoneal injection; the third group was a normal feeding group (5).

5.1.3, uniformly treating the model without death in the construction process and after 7 days, taking the aorta of the mouse, and counting the survival curve and the molding rate.

5.2, results

The results of the model formation rate are shown in fig. 12 and fig. 13, in fig. 13, the total number of mice in the IL-33 treatment group is 18, the model formation rate is 11, and the model formation ratio is 61.1%; wherein, the proportion of aortic dissection (not ruptured) is 4, the proportion is 22.2, the proportion of aortic dissection (ruptured) is 7, the proportion is 38.9%; the total number of mice in the normal saline group is 10, the modulus of formation is 8, and the proportion of the modulus of formation is 80%; wherein the aortic dissection (not ruptured) is 2 in 20%, and the aortic dissection (ruptured) is 6 in 60%; the percentage of total module and aortic dissection (rupture) in mice in the IL-33 treated group were lower than in the saline group.

In fig. 12, a bar graph represents the total modulus. Wherein the black column portion in the bar graph represents the proportion of aortic dissection that did not rupture; the white filled bar graph section represents the proportion of aortic dissection where rupture occurred; cracking indicates death due to interlayer cracking during molding.

The results of the mouse survival curves of the IL-33 treated group and the saline group are shown in FIG. 14, and the results of FIG. 14 show that the mice did not die within 14 days of the BAPN feeding method for constructing the mouse aorta model; from the day 14 component treatment, the survival rate of mice in the IL-33 treated group was higher than that in the normal saline group, indicating that IL-33 had a therapeutic effect on aortic dissection.

The results show that the mice in the IL-33 treatment group have obviously reduced arterial rupture rate and interlayer incidence rate and obviously improved survival condition compared with the mice in the normal saline group.

The present invention has been described in detail above. It will be apparent to those skilled in the art that the invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with reference to specific embodiments, it will be appreciated that the invention can be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. The use of some of the essential features is possible within the scope of the claims attached below.

Claims (9)

1. Use of IL-33 characterized by: the application is the application of IL-33 in preparing the medicine for preventing and/or treating aortic dissection.
2. 2. Use according to claim 1, characterized in that: the aortic dissection is a thoracic aortic dissection.
3. 3. Use according to claim 2, characterized in that: the prevention and/or treatment of aortic dissection comprises inhibiting or reducing the formation of thoracic aortic dissection.
4. 4. Use according to claim 3, characterized in that: the inhibiting or reducing formation of thoracic aortic dissection inhibits formation of thoracic aortic lesions or reduces the extent of thoracic aortic lesions.
5. 5. Use according to claim 2, characterized in that: the prevention and/or treatment of aortic dissection comprises inhibiting organ damage caused by thoracic aortic dissection.
6. 6. Use according to claim 5, characterized in that: the inhibition of organ injury caused by thoracic aortic dissection comprises reducing the extracellular volume of the heart and/or reducing the content of organ injury markers.
7. 7. Use according to claim 6, characterized in that: the organ injury markers include troponin, aspartate aminotransferase, alanine aminotransferase and/or urea nitrogen.
8. 8. Use according to any one of claims 1 to 7, characterized in that: the IL-33 is recombinant human IL-33.
9. 9. Use according to any one of claims 1 to 7, characterized in that: the medicament for preventing and/or treating aortic dissection is a medicament for gastrointestinal administration, a medicament for intravenous injection administration or a medicament for subcutaneous embedding administration.

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