Application of scutellarein in preparation of medicine for relieving pulmonary arterial hypertension

Abstract

The invention discloses application of scutellarein in preparation of a medicine for relieving pulmonary arterial hypertension, and belongs to the technical field of biological medicine. According to the application disclosed by the invention, the scutellarein can be used for reducing the expression of GSDMD-NT, NLRP3, ASC, Cleved-caspase1, IL-18 and IL-1beta, relieving the migration of smooth muscle cells of the pulmonary artery, mitochondrial injury, reducing the inflammation level and the like, so that the pulmonary hypertension can be effectively relieved. The scutellarein has a good curative effect on relieving the pulmonary arterial hypertension, has a good medicinal value prospect, and can be developed into a novel medicine for treating the pulmonary arterial hypertension.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to the application of scutellarin in preparing medicines for alleviating pulmonary hypertension. Background Art

[0002] Pulmonary arterial hypertension (PAH) is a very harmful clinical disease, which is characterized by the continuous increase of pulmonary vascular resistance, which in turn causes right ventricular hypertrophy, and may eventually lead to right heart failure and even death. This disease not only seriously threatens the physical and mental health of patients, but also brings a heavy burden to social medical resources. The causes of PAH are complicated, including environmental factors and profoundly affected by genetic factors, which lead to abnormalities in pulmonary vascular structure and function. Congenital heart disease, left heart failure, valvular disease, chronic obstructive pulmonary disease, rheumatic immune disorders and familial genetic diseases are all potential causes of PAH. Clinically, PAH patients often experience abnormal breathing difficulties, and may also be accompanied by a variety of symptoms such as chest tightness, dizziness, and fatigue. What is particularly worrying is that children affected by PAH may have a significant impact on their growth and development, and may have developmental abnormalities or delays. However, unfortunately, the current society's understanding of PAH is still very limited, especially in China, where the overall diagnosis and treatment level needs to be improved. Therefore, we urgently need to find effective PAH prevention and treatment strategies to reduce the huge impact of this disease on patients and society, and provide strong guarantees for the physical and mental health of patients and the rational use of social medical resources.

[0003] Scutellarin (Sc) is a naturally occurring flavonoid compound with a wide range of sources, including the whole plant of Cornaceae, the whole plant of Scutellaria barbata, the whole plant of Verbenaceae, the noble plum of Rosaceae, and various plants of Asteraceae, Scrophulariaceae, and Cornaceae. As the core active ingredient in many traditional Chinese medicines, Sc is widely recognized for its significant anti-inflammatory and antioxidant properties, and is therefore highly favored in food and medical products. Studies have shown that Sc exhibits significant therapeutic effects in the treatment of various cardiovascular and pulmonary diseases, such as cardiac hypertrophy, hypertension, angiogenesis, stroke, obstructive pulmonary disease, and pulmonary fibrosis. However, despite its great potential in many fields, Sc has not yet been included in the clinical management of pulmonary hypertension, and no relevant research reports in this field have been reported. Summary of the invention

[0004] The purpose of the present invention is to provide the use of baicalein in the preparation of a medicine for alleviating pulmonary hypertension, so as to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] The invention provides application of scutellariae in preparing medicine for alleviating pulmonary hypertension.

[0007] Preferably, the pulmonary hypertension includes pulmonary hypertension induced by Monocrotaline (MCT) and hypoxic pulmonary hypertension induced by hypoxia (10%) + Su5416 (VEGF receptor inhibitor) (Hypoxia + Su5416, HxSu).

[0008] The present invention also provides the use of baicalein in preparing medicine for reducing the level of inflammatory factors.

[0009] Preferably, the inflammatory factors include TNF-α, IL-1β and IL-6.

[0010] The invention also provides the use of scutellariae in preparing a medicine for inhibiting the migration of pulmonary artery smooth muscle cells.

[0011] Preferably, the pulmonary artery smooth muscle cell migration is hypoxia-induced pulmonary artery smooth muscle cell migration.

[0012] The present invention also provides the use of scutellarin in preparing a medicine for inhibiting pyroptosis of pulmonary artery smooth muscle cells.

[0013] The invention also provides the use of scutellariae in preparing a medicine for alleviating mitochondrial damage of pulmonary artery smooth muscle cells.

[0014] Based on the above technical solution, the present invention has the following technical effects:

[0015] The present invention finds that scutellarin can effectively alleviate pulmonary hypertension by down-regulating the expression of GSDMD-NT, NLRP3, ASC, Cleaved-caspase 1, IL-18, IL-1β, reducing pulmonary artery smooth muscle cell migration, mitochondrial damage, and reducing inflammation levels. Scutellarin has a good therapeutic effect on relieving pulmonary hypertension, has good medicinal value prospects, and can be developed into a new drug for treating pulmonary hypertension. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0017] Figure 1aThe right ventricular pressure of rats with MCT-induced pulmonary hypertension (left) and mice with hypoxic pulmonary hypertension (right) under baicalein treatment (n=6);

[0018] Figure 1b Right heart echocardiogram of rats with MCT-induced pulmonary hypertension treated with baicalein (n=6);

[0019] Figure 1c This is the right heart echocardiogram of mice with hypoxic pulmonary hypertension treated with baicalein (n=6);

[0020] Figure 1d HE staining of lung tissues of rats with MCT-induced pulmonary hypertension treated with baicalein (n=6);

[0021] Figure 1e HE staining of lung tissue of mice with hypoxic pulmonary hypertension treated with baicalein (n=6);

[0022] Figure 1f αSMA staining of lung tissues of rats with MCT-induced pulmonary hypertension under baicalein treatment (n=6);

[0023] Figure 1g αSMA staining of lung tissues of mice with hypoxic pulmonary hypertension treated with baicalein (n=6);

[0024] Figure 2a Serum inflammatory factor levels in rats with MCT-induced pulmonary hypertension and mice with hypoxic pulmonary hypertension treated with baicalein (n=6);

[0025] Figure 3a is the level of hypoxia-induced migration of human pulmonary artery smooth muscle cells under baicalein treatment (n=6);

[0026] Figure 4a The expression levels of pyroptotic signals NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β in lung tissue of rats with MCT-induced pulmonary hypertension and mice with hypoxic pulmonary hypertension under baicalein treatment (n=6);

[0027] Figure 4b Baicalein reduces the expression levels of hypoxia-induced pyroptosis signals GSDMD-NT, NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β in human pulmonary artery smooth muscle cells by activating SIRT1 signaling (n=6);

[0028] Figure 5a Baicalein increased the mitochondrial membrane potential level of human pulmonary artery smooth muscle cells induced by hypoxia (n=6);

[0029] Figure 5b Baicalein reduces the level of mitochondrial superoxide in human pulmonary artery smooth muscle cells induced by hypoxia (n=6). DETAILED DESCRIPTION

[0030] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0031] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0032] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0033] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0034] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0035] The technical solutions described in the present invention, unless otherwise specified, are all conventional solutions in the art, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or are publicly available.

[0036] The embodiment of the present invention provides the use of baicalein in preparing a drug for alleviating pulmonary hypertension. It should be noted that baicalein can alleviate pulmonary hypertension, so it can be prepared into a drug for alleviating pulmonary hypertension.

[0037] In some specific embodiments, the pulmonary hypertension includes MCT-induced pulmonary hypertension and hypoxic pulmonary hypertension. It should be noted that scutellarin can reduce MCT- or hypoxia-induced pulmonary hypertension, and can be prepared into a drug for reducing MCT- or hypoxia-induced pulmonary hypertension.

[0038] The embodiment of the present invention provides the use of baicalein in preparing a medicine for reducing the level of inflammatory factors.

[0039] In some specific embodiments, the inflammatory factors include TNF-α, IL-1β and IL-6. It should be noted that baicalein can reduce pulmonary hypertension by reducing the activity of TNF-α, IL-1β and IL-6 in the blood, so baicalein can be prepared into a drug for reducing blood inflammatory factors.

[0040] The embodiment of the present invention provides the use of scutellarin in the preparation of a drug for inhibiting the migration of pulmonary artery smooth muscle cells. It should be noted that scutellarin can reduce the migration of pulmonary artery smooth muscle cells and thus reduce pulmonary hypertension. Therefore, scutellarin can be prepared into a drug for reducing the migration of pulmonary artery smooth muscle cells and thus used to reduce pulmonary hypertension.

[0041] In some specific embodiments, the pulmonary artery smooth muscle cell migration is hypoxia-induced pulmonary artery smooth muscle cell migration.

[0042] The embodiment of the present invention provides the use of baicalein in the preparation of a drug for down-regulating the expression of GSDMD-NT, NLRP3, ASC, Cleaved-caspase1, IL-18, and IL-1β. It should be noted that baicalein can down-regulate the expression of GSDMD-NT, NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β, thereby alleviating pulmonary hypertension. Therefore, baicalein can be made into a drug for down-regulating the expression of GSDMD-NT, NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β for alleviating pulmonary hypertension.

[0043] The embodiment of the present invention provides the use of baicalein in preparing a drug for inhibiting pyroptosis of pulmonary artery smooth muscle cells.

[0044] The embodiment of the present invention provides the use of scutellarin in the preparation of a drug for reducing mitochondrial damage to pulmonary artery smooth muscle cells. It should be noted that scutellarin can upregulate the mitochondrial membrane potential level of pulmonary artery smooth muscle cells and downregulate the mitochondrial superoxide level of pulmonary artery smooth muscle cells, thereby reducing mitochondrial damage to pulmonary artery smooth muscle cells. Therefore, scutellarin can be made into a drug that upregulates the mitochondrial membrane potential level of pulmonary artery smooth muscle cells and downregulates the mitochondrial superoxide level of pulmonary artery smooth muscle cells to reduce mitochondrial damage to pulmonary artery smooth muscle cells.

[0045] 1. Cell culture and treatment: Human HASMC (CP-H243) cells and human HASMC culture medium (CM-H243) were purchased from Wuhan Pronocell Life Science Co., Ltd.; human HASMC of passage 3-5 were used in the experiment. In order to simulate a hypoxic environment, human HASMC were cultured in an environment of 1% O2 for 24 h, during which 50 mg / kg scutellarin was added.

[0046] Example 1

[0047] In this example, in order to study the relationship between the use of baicalein and pulmonary hypertension, pulmonary hypertension in rats or mice was modeled using MCT or hypoxia, and baicalein was used for intervention.

[0048] 1. MCT-induced pulmonary hypertension in rats: modeling period is 3 weeks

[0049] 1. Control group: subcutaneous and intraperitoneal injection of equal amount of solvent control;

[0050] 2. Sc group: intraperitoneal injection of 50 mg / kg Sc, once a day;

[0051] 3. MCT group: subcutaneous injection of 60 mg / kg MCT once at the beginning of the experiment; intraperitoneal injection of an equal amount of solvent control once a day;

[0052] 4. MCT+Sc group: subcutaneous injection of an equal amount of solvent control; intraperitoneal injection of 50 mg / kg Sc, once a day.

[0053] 2. HxSu-induced pulmonary hypertension in mice, modeling period is 4 weeks

[0054] 1. Control group: intraperitoneal injection of equal amount of solvent control;

[0055] 2. Sc group: intraperitoneal injection of 50 mg / kg Sc, once a day; at the same time, intraperitoneal injection of an equal amount of solvent control, once a week;

[0056] 3. HxSu group: intraperitoneal injection of 20 mg / kg Su5416 once a week; at the same time, intraperitoneal injection of an equal amount of solvent control once a day;

[0057] 4. HxSu+Sc group: intraperitoneal injection of 20 mg / kg Su5416 once a week; and intraperitoneal injection of 50 mg / kg Sc once a day.

[0058] At the end of the experiment, the experimental animals were anesthetized by intraperitoneal injection of sodium pentobarbital and fixed on a small animal ultrasound workbench or laboratory table. When measuring right ventricular ultrasound, the animal's chest was exposed and the hair was removed. The right ventricular ultrasound of the model animal was measured under the operation of a professional echocardiography technician. When measuring right ventricular pressure, the skin on the right side of the model animal's neck was exposed, the hair was removed and the skin was cut open, the neck muscles were bluntly separated to expose the jugular vein, the distal end of the jugular vein was ligated, a small incision was made in front of the ligature, the proximal end (including the catheter) was ligated after the fiber optic catheter was inserted 1-2 cm, and then the catheter was slowly inserted and the pressure waveform was observed to determine whether it entered the right ventricle and record the intraventricular pressure.

[0059] The results showed that the administration of scutellarin effectively reversed the MCT-induced and HxSu-induced right ventricular pressure ( Figure 1a ) and right ventricular ultrasound ( Figure 1b ) abnormalities. At the same time, baicalein can improve the increase in RV / (LV+S) ratio in rats and mice caused by MCT and HXu ( Figure 1c In addition, scutellarin reversed the pulmonary artery thickening induced by MCT and HxSu in rats and mice, respectively ( Figure 1d and 1e ), and the fluorescence enhancement of αSMA ( Figure 1f and 1g ). This indicates that the use of scutellariae is strongly negatively correlated with pulmonary hypertension.

[0060] Example 2

[0061] In the present embodiment, in order to study the relationship between the use of scutellariae and the level of inflammation in the development of pulmonary hypertension, the levels of inflammatory factors TNF-α, IL-1β, and IL-6 in the serum of model animals were measured. After measuring the echocardiogram and right ventricular pressure, the model animals were killed by cervical dislocation, the chest cavity was opened aseptically, the heart and lungs were exposed, and blood samples were obtained from the left ventricle, centrifuged at 4°C and 2000rpm, and the supernatant was the serum sample.

[0062] Inflammatory factor (TNF-α, IL-1β, IL-6) detection:

[0063] 1) All reagents should be thoroughly mixed before use;

[0064] 2) Serum samples were diluted 1:1 with specimen diluent and 50 μL was added to the reaction well;

[0065] 3) Add 50 μL of the diluted standard and sample to the reaction wells. Immediately add 50 μL of biotin-labeled antibody to all wells. Seal the plate, gently shake and mix, and incubate at 37°C for 1 hour.

[0066] 4) Remove the liquid in the wells, wash with washing solution for 30 seconds, remove the washing solution and pat dry, and repeat 3 times.

[0067] 5) Add 80 μL of streptavidin-HRP to each well, shake gently to mix, and incubate at 37°C for 30 min.

[0068] 6) Remove the liquid in the wells, wash with washing solution for 30 seconds, then remove the washing solution and pat dry, repeat 3 times.

[0069] 7) Add 50 μL of substrate A and B to each well, gently shake to mix, and incubate at 37°C in the dark for 10 min.

[0070] 8) Quickly add 50 μL of stop solution and immediately measure the OD value of each well at a wavelength of 450 nm.

[0071] The results showed that the administration of scutellarin effectively reversed the abnormal increase of serum inflammatory factors induced by MCT in rats and HxSu in mice ( Figure 2a ). This indicates that the use of scutellariae is strongly negatively correlated with the inflammatory state in pulmonary hypertension.

[0072] Example 3

[0073] Pulmonary hypertension is characterized by increased migration of pulmonary artery smooth muscle cells. This example tests whether scutellarin regulates the migration of pulmonary artery smooth muscle cells. The test material is human pulmonary artery smooth muscle cells.

[0074] Cell migration (scratch assay + Transwell assay): For the scratch assay, after cleaning the cells, gently and evenly scrape a straight cell-free area in the center of the culture dish with a 1 ml pipette tip. Next, the cells were treated according to the predefined modeling plan for 48 hours and then examined under a microscope. For the Transwell experiment, the lower chamber of the plate contained culture medium supplemented with 10% FBS. The cell suspension was prepared using low serum (2% FBS) culture medium. Once the cells were counted, they were carefully introduced into the upper chamber. The cells were subjected to the modeling protocol for 48 hours. The migrated cells were fixed with 4% paraformaldehyde for 20 minutes at room temperature. After rinsing, the cells were stained with crystal violet dye and examined under a microscope.

[0075] Cell scratch assay showed that baicalein effectively inhibited the hypoxia-induced increase in migration of human pulmonary artery smooth muscle cells. Transwell assay results also showed that baicalein effectively inhibited the hypoxia-induced increase in migration of human pulmonary artery smooth muscle cells ( Figure 3a). This indicates that baicalein can effectively inhibit the migration of pulmonary artery smooth muscle cells.

[0076] Example 4

[0077] In this example, the effect of baicalein on cell pyroptosis in two animal models of pulmonary hypertension and a hypoxia-induced human pulmonary artery smooth muscle cell model was evaluated. The test material was human pulmonary artery smooth muscle cells.

[0078] Protein concentration detection: Take 1.2ml of protein standard preparation solution and add it to a tube of protein standard (30mg BSA), and prepare a 25mg / ml protein standard solution after fully dissolving; Take an appropriate amount of 25mg / ml protein standard and dilute it to a final concentration of 0.5mg / ml; According to the number of samples, prepare an appropriate amount of BCA working solution by adding 50 volumes of BCA reagent A to 1 volume of BCA reagent B (50:1), and mix thoroughly; For protein concentration detection, add 0, 1μl, 2μl, 4μl, 8μl, 12μl, 16μl, 20μl of the standard to 9 In the standard wells of the 6-well plate, add standard diluent to make up to 20μl, which is equivalent to standard concentrations of 0, 0.025mg / ml, 0.05mg / ml, 0.1mg / ml, 0.2mg / ml, 0.3mg / ml, 0.4mg / ml, and 0.5mg / ml, respectively; add appropriate volume of sample to the sample wells of the 96-well plate; if the sample is less than 20μl, add standard diluent to make up to 20μl; add 200μl BCA working solution to each well and place at 37℃ for 20 minutes to 30 minutes; measure the absorbance wavelength at 562nm with an enzyme reader; calculate the protein concentration of the sample based on the standard curve and the sample volume used.

[0079] Immunoblotting: prepare separation gel (5ml / gel), let stand for about 30 minutes; prepare concentrated gel (2ml / gel); inject concentrated gel into the upper end of separation gel, be careful to avoid bubbles; insert comb, wait for concentrated gel to solidify; put gel into electrophoresis tank, add 1× electrophoresis buffer to both upper and lower tanks; load: the loading volume is generally 15μl-25μl; electrophoresis, start with constant voltage 60-80V, after running through concentrated gel, increase current to 100V-120V, electrophoresis time is determined according to the size of target protein and marker position; cut gel, cut gel according to marker indication and target band position; after marking PVDF membrane, immerse in methanol for 1 minute, then put it together with 4 sheets of 3 Immerse 100 mm filter paper and sponge in transfer buffer for 15 minutes; prepare a "sandwich cake" in the following order: fiber pad-filter paper-PVDF membrane-gel-filter paper-fiber pad; transfer, constant current 0.2A, 2-3 hours; connect the positive electrode (red) on one side of the PVDF membrane and the negative electrode (black) on the other side of the gel; after transfer, wash the membrane with 1×TBST at room temperature for 10 minutes; incubate with skim milk powder blocking solution at room temperature for 1 hour; wash the membrane 3 times with TBST, 10 minutes each time; incubate the membrane with primary antibody at 4°C overnight; wash the membrane 3 times with TBST, 10 minutes each time; add secondary antibody (usually 1:2000 dilution), shake gently at room temperature for 1 hour; wash the membrane 3 times with TBST, 5 minutes each time; develop.

[0080] Immunofluorescence: dewax paraffin sections; antigen retrieval; permeabilization with Triton 100X; wash three times with PBS, 5 minutes each time; block with room temperature blocking solution for 60 minutes; incubate with primary antibody, store in a 4°C refrigerator overnight; rewarm at room temperature for about 30 minutes; wash sections with PBST three times, 5 minutes each time; add fluorescent secondary antibody, incubate at 37°C in a wet box away from light for 1 to 1.5 hours; wash sections with PBST three times, 5 minutes each time; counterstain nuclei, add DAPI, incubate in the dark for 10 minutes-15 minutes; seal sections with sealing solution containing anti-fluorescence quencher; observe under a microscope.

[0081] Immunoblotting confirmed that baicalein significantly downregulated the expression of pyroptosis signals NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β in the lung tissues of MCT-induced pulmonary hypertension rats and hypoxia-induced pulmonary hypertension mice ( Figure 4a ). In addition, in vitro studies have found that baicalein also effectively downregulated the expression levels of NLRP3, ASC, Cleaved-caspase 1, IL-18, and IL-1β, the pyroptotic signals induced by hypoxia in human pulmonary artery smooth muscle cells ( Figure 4b ). This indicates that baicalein has a protective effect on pyroptosis of pulmonary artery smooth muscle cells in pulmonary hypertension.

[0082] Example 5

[0083] In this example, the effect of baicalein on mitochondria in a hypoxia-induced human pulmonary artery smooth muscle cell model was evaluated. The test material was human pulmonary artery smooth muscle cells.

[0084] JC-1 (mitochondrial membrane potential) staining and MitoSOX (mitochondrial superoxide) staining: After cleaning the cells with JC-1 staining buffer, they were incubated with JC-1 staining working solution at a 1:1 ratio for 30 minutes in a dark environment. On the other hand, the cells in the culture dish were completely covered with MitoSOX red indicator. They were then incubated in the dark at 37°C for 10 minutes. Subsequently, the cells were rinsed and the nuclei were stained with Hochester staining solution. Finally, the stained cells were observed under a fluorescence confocal microscope.

[0085] JC-1 (mitochondrial membrane potential) staining confirmed that baicalein significantly increased the hypoxia-induced mitochondrial membrane potential of human pulmonary artery smooth muscle cells ( Figure 5a MitoSOX (mitochondrial superoxide) staining confirmed that baicalein significantly reduced the level of mitochondrial superoxide in human pulmonary artery smooth muscle cells induced by hypoxia ( Figure 5b ). The results showed that baicalein protected the mitochondrial function of pulmonary artery smooth muscle cells in pulmonary hypertension.

[0086] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation methods of the present invention. For ordinary technical users in the relevant field, other different forms of changes or modifications can be made on the basis of the above description. It is not necessary and impossible to list all the implementation methods here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. Application of baicalein in the preparation of drugs for alleviating pulmonary hypertension.

2. The use according to claim 1, characterized in that: The pulmonary hypertension includes MCT-induced pulmonary hypertension and hypoxic pulmonary hypertension.

3. Application of baicalin in the preparation of drugs for reducing the levels of inflammatory factors.

4. The use according to claim 3, characterized in that: The inflammatory factors include TNF-α, IL-1β and IL-6.

5. Application of baicalein in the preparation of drugs for inhibiting the migration of pulmonary artery smooth muscle cells.

6. The use according to claim 5, characterized in that: The pulmonary artery smooth muscle cell migration is hypoxia-induced pulmonary artery smooth muscle cell migration.

7. Application of baicalin in the preparation of drugs for inhibiting pyroptosis of pulmonary artery smooth muscle cells.

8. Application of baicalein in the preparation of drugs for reducing mitochondrial damage in pulmonary artery smooth muscle cells.

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