Application of decurrin in preparation of products for myocardial ischemia-reperfusion injury diseases

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of decursin in preparation of a product for treating myocardial ischemia-reperfusion injury diseases. The decurrin can reduce the myocardial infarction area, improve the myocardial vitality, improve the systolic function and reverse injury caused by myocardial ischemia reperfusion, can be used for preparing products for the myocardial ischemia reperfusion injury disease, and provides a new predictable means for prevention, treatment and recovery of the myocardial ischemia reperfusion injury disease.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and particularly relates to the application of purpurogenol in preparing products for treating myocardial ischemia-reperfusion injury. Background Art

[0002] Decursin is a fat-soluble Chinese medicine monomer extracted from Chinese angelica, CAS No.: 5928-25-6, and its structural formula is shown in Formula I:

[0003]

[0004] In recent years, a large number of studies have shown that purpurogenol has great potential in the prevention and treatment of tumors and inflammation. At the same time, its activity for other diseases has also been discovered one after another, such as: CN118178400A is an application of purpurogenol in the preparation of intestinal disease drugs, disclosing that the effect of treating inflammatory bowel disease is achieved by inhibiting the expression of NLRP3 inflammasome protein; CN116585304A is an acute liver injury protective drug and its preparation method, disclosing that purpurogenol inhibits APAP-induced ALT and AST activities to improve liver function and then is used for acute liver injury protection; CN115531375A is an application of purpurogenol in the preparation of drugs for inhibiting the growth of Helicobacter pylori, disclosing that purpurogenol has a significant inhibitory effect on Helicobacter pylori.

[0005] Myocardial ischemia-reperfusion injury refers to the damage to local myocardial cells caused by oxidative stress and inflammatory response during hypoxia and reperfusion when blood flow to the heart is restored after blood supply is interrupted. This process not only leads to cell apoptosis and necrosis, but may also cause heart failure and other serious cardiovascular complications. Therefore, it is crucial to find effective intervention methods to reduce myocardial ischemia-reperfusion injury. Summary of the invention

[0006] The present invention finds that purpurogenol can reverse the damage caused by myocardial ischemia-reperfusion, thus providing a new and predictable means for the prevention, treatment and recovery of myocardial ischemia-reperfusion injury.

[0007] Purpurogenous chamomile can reverse myocardial ischemia-reperfusion-induced damage by reducing myocardial infarction area, and / or increasing myocardial vitality, and / or improving cardiac contractile function, providing support for purpurogenous chamomile can reverse myocardial ischemia-reperfusion-induced damage, and providing a theoretical basis for the prevention, treatment and recovery of myocardial ischemia-reperfusion injury diseases.

[0008] The present invention provides the application of purpurogenol in preparing a product for treating myocardial ischemia-reperfusion injury. The product prepared by purpurogenol in treating myocardial ischemia-reperfusion injury can be a medicine for treatment, a health product for prevention or recovery, a medical device product for prevention, treatment or recovery, or a medical engineering material for prevention, treatment or recovery.

[0009] Purpurogenol prevents, and / or treats, and / or restores myocardial ischemia-reperfusion injury diseases by reversing the damage caused by myocardial ischemia-reperfusion.

[0010] Purpurogenol can reverse the damage caused by myocardial ischemia-reperfusion by reducing myocardial infarction area, and / or increasing myocardial vitality, and / or improving cardiac contractile function.

[0011] The invention provides a product for myocardial ischemia-reperfusion injury disease, which contains purpurogenol.

[0012] Purpurogenol prevents, and / or treats, and / or restores myocardial ischemia-reperfusion injury diseases by reversing the damage caused by myocardial ischemia-reperfusion.

[0013] Purpurogenol can reverse the damage caused by myocardial ischemia-reperfusion by reducing myocardial infarction area, and / or increasing myocardial vitality, and / or improving cardiac contractile function.

[0014] The product for myocardial ischemia-reperfusion injury disease provided by the present invention can be a therapeutic medicine, a health product for prevention or recovery, a medical device product for prevention, treatment or recovery, or a medical engineering material for prevention, treatment or recovery.

[0015] The product for myocardial ischemia-reperfusion injury disease provided by the present invention also contains other ingredients for the prevention, and / or treatment, and / or health care of myocardial ischemia-reperfusion injury disease, which produce synergistic, and / or auxiliary, and / or enhancing effects with purslane scutellariae, improve the preventive activity, and / or therapeutic activity, and / or restore the health care activity of myocardial ischemia-reperfusion injury disease, reduce the side effects of the prevention, and / or treatment, and / or health care of myocardial ischemia-reperfusion injury disease, improve the sequelae of myocardial ischemia-reperfusion injury disease, and enhance the effects of the prevention, and / or treatment, and / or health care of myocardial ischemia-reperfusion injury disease.

[0016] The product for treating myocardial ischemia-reperfusion injury provided by the present invention further contains pharmaceutical excipients, and / or excipients for health care products, and / or medical excipients.

[0017] When the product for myocardial ischemia-reperfusion injury disease provided by the present invention is used as a drug for myocardial ischemia-reperfusion injury disease, it can be prepared into any dosage form, which is convenient for patients to use and meets the prevention and / or treatment needs of the disease. It can be a solid preparation, a semi-solid preparation, a liquid preparation, a gas preparation, a solid preparation such as a pill, a powder, a tablet, a granule, a capsule, etc., a semi-solid preparation such as a paste, an ointment, etc., a liquid preparation such as an injection, a solution, a perfumed water, etc., a gas preparation such as an aerosol, a partial inhalation, etc. To meet the needs of different routes of administration, such as pills, powders, tablets, granules, capsules, solutions, perfumed water, etc. for gastrointestinal administration, injections for injection, pastes, ointments, etc. for skin administration, aerosols, partial inhalations for respiratory administration, sublingual tablets, films, etc. for mucosal administration.

[0018] The results of animal experiments showed that purpurogenol can significantly improve the deterioration of cardiac function after myocardial ischemia-reperfusion injury, thereby reducing the area of ​​myocardial infarction and ultimately improving the survival rate of mice.

[0019] When the product for myocardial ischemia-reperfusion injury disease provided by the present invention is used as a medical device for myocardial ischemia-reperfusion injury disease, it can be prepared into the form of an invasive device, and / or an implantable device, and / or a human body contacting device, etc., to play a role in preventing, and / or treating, and / or restoring myocardial ischemia-reperfusion injury disease.

[0020] When the product for myocardial ischemia-reperfusion injury disease provided by the present invention is used as a medical engineering material for myocardial ischemia-reperfusion injury disease, it can invade, and / or be implanted, and / or contact the human body, etc., to play a role in preventing, and / or treating, and / or restoring myocardial ischemia-reperfusion injury disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a diagram of the experimental results of the experimental scheme of the present invention, electrocardiogram monitoring, TTC staining, PET-CT analysis, and echocardiography. DETAILED DESCRIPTION

[0022] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0023] Experimental protocol:

[0024] This study verified the effect of decursin on myocardial ischemia-reperfusion injury in mice. The specific protocol of the animal experiment is detailed in Figure 1 a. Settings:

[0025] 1) Myocardial ischemia-reperfusion injury model sham operation group, i.e. Sham group; no drug treatment was given.

[0026] 2) The myocardial ischemia-reperfusion injury model was operated on and treated with a solute (vehicle). The solute was used to dissolve Decursin, and served as the negative control group for Decursin intervention, i.e., the I / R group. Drug administration: The solute was injected on the third day after the myocardial ischemia-reperfusion injury model was operated on, with a total injection volume of 100 μL.

[0027] 3) Myocardial ischemia-reperfusion model surgery and decursin treatment group, i.e. I / R+Decursin group; drug administration: injection on the third day after myocardial ischemia-reperfusion model surgery, according to the decursin dosage of 2 mg / kg / mouse, and the total injection volume of 100 μL.

[0028] Echocardiography, positron emission tomography-computed tomography (PET-CT), and triphenyltetrazolium chloride (TTC) staining were performed on the 7th day after myocardial ischemia-reperfusion injury surgery.

[0029] Methodology:

[0030] Myocardial ischemia-reperfusion model

[0031] The myocardial ischemia-reperfusion model in mice was established by ligating the left anterior descending coronary artery and reperfusing. The specific steps were as follows: the mice were anesthetized with 2% isoflurane, and then a tracheal tube was inserted under visualization and connected to a mechanical ventilation device equipped with oxygen supplementation. Each mouse was placed supine on a heating pad. Next, the chest hair was shaved, disinfected with 75% alcohol, and then the thoracotomy was performed in the fourth intercostal space on the left side. The pericardium was removed to fully expose the heart. To induce myocardial ischemia, the left anterior descending coronary artery was observed under a microscope, and a temporary suture was performed below the left atrial margin with 8-0 silk thread. The change in the color of the left ventricle confirmed the complete occlusion of the left anterior descending coronary artery. After completing the ligation, the chest cavity was closed and the skin was sutured. After suturing, ischemia lasted for 45 minutes, followed by reperfusion. After surgery, the mice received appropriate analgesic treatment and infection prevention measures. In the sham operation group, all other surgical steps were the same except for the ligation of the left anterior descending coronary artery (i.e., sutured below the left anterior descending coronary artery without tying a knot).

[0032] Mouse ECG monitoring

[0033] The steps of intraoperative ECG monitoring in mice include: placing the electrocardiograph and ECG acquisition device on a horizontal surface, connecting the power supply and electrodes. The electrode connection method is: left forelimb (LA lead), right forelimb (RA lead), left hindlimb (LL lead) and right hindlimb (RL lead). Turn on the ECG machine and set the power supply to alternating current (AC). Configure filters for electromyography (EMG) suppression and hum suppression (HUM). Set the paper speed to 50 mm / s, the calibration to 1 mV, and the sensitivity to 2 mV. The focus of monitoring is the changes in the ECG before and after surgery, paying special attention to changes in the ST interval.

[0034] 2,3,5-Triphenyltetrazolium chloride staining

[0035] According to the method of relevant literature, heart tissues of different treatment groups were collected. Use a razor to slice at the level of papillary muscles and cut 1-2 mm thick heart tissue sections. The sections were incubated in 1% 2,3,5-triphenyltetrazolium chloride at 37°C for 15 minutes and then immersed in 4% formalin overnight to distinguish non-infarcted areas from infarcted areas. Unstained areas (white) represent infarcted areas, which can be clearly identified after staining.

[0036] Positron emission tomography-computed tomography (PET-CT) imaging

[0037] PET-CT imaging was performed on the seventh day after myocardial ischemia-reperfusion surgery. Mice were anesthetized with 1.5% isoflurane and injected intravenously with 150 μCi of 18F-FDG. After a 1-hour uptake period, PET-CT scanning was performed using the Inveon multimodal platform. During the scan, image processing was performed using the Inveon acquisition workbench (v1.5.0.28). Image reconstruction was performed using the three-dimensional ordered subset expectation maximization (OSEM) method for 10-minute CT scans and 10-minute static PET scans. Based on the CT results, the three-dimensional region of interest (ROI) around the heart was defined as a circular area. Image analysis was performed using the Inveon Research Studio software, and the mean standardized uptake value (SUV) of the ROI was automatically calculated.

[0038] Echocardiography

[0039] Left ventricular function was assessed using the Vevo 2100 imaging system (Visual Ultrasound) as described previously. Mice were anesthetized with 1.5% isoflurane inhalation, and their limbs were fixed on the operating table. The probe was placed vertically in the left ventricle of the mice. Echocardiographic data and M-mode images were acquired and analyzed on the seventh postoperative day, and echocardiographic parameters such as left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were automatically measured by the “left ventricular tracking” mode, which effectively tracks the endocardial border.

[0040] Experimental results:

[0041] To ensure a high success rate of surgical modeling, each mouse underwent electrocardiogram monitoring before and after surgery. The ST segment elevation method was used to determine the precise ligation of the left anterior descending artery ( Figure 1 b), minimize modeling bias.

[0042] The results of 2,3,5-triphenyltetrazolium chloride staining showed that compared with the mice in myocardial ischemia-reperfusion surgery (I / R group), the Decursin group (i.e., I / R+Decursin group) significantly reduced myocardial infarction area ( Figure 1 c, d).

[0043] PET-CT analysis of myocardial viability showed that the mean standardized uptake value (SUV) in the myocardial ischemia-reperfusion group (I / R group) was significantly reduced, while that in the group treated with Decursin (i.e., I / R+Decursin group) was significantly increased ( Figure 1 e, f).

[0044] In addition, cardiac contractile function was evaluated by two-dimensional echocardiography, and the results showed that Decursin treatment (i.e., I / R+Decursin group) effectively reversed the decrease in left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVFS) caused by myocardial ischemia-reperfusion, and significantly enhanced the cardiac contractile function ( Figure 1 gi).

[0045] in conclusion:

[0046] The results of animal experiments showed that Decursin has a significant protective effect on myocardial ischemia-reperfusion injury in mice. Decursin effectively reversed the damage caused by ischemia-reperfusion by reducing myocardial infarction area, increasing myocardial vitality and improving cardiac contractile function. These results support the potential of Decursin in the treatment of cardiovascular diseases and provide a theoretical basis for its clinical application. Further research will help reveal its specific mechanism of action and the feasibility of clinical application.

Claims

1. Application of purpurogenol in the preparation of products for myocardial ischemia-reperfusion injury.

2. The use according to claim 1, characterized in that: The products are medicines, and / or health products, and / or medical devices, and / or medical engineering materials.

3. A product for myocardial ischemia-reperfusion injury, characterized in that: Contains purpurogenol.

4. A product for myocardial ischemia-reperfusion injury according to claim 3, characterized in that: The products are medicines, and / or health products, and / or medical devices, and / or medical engineering materials.

5. The product for myocardial ischemia-reperfusion injury according to claim 4, characterized in that: The invention also contains other ingredients for preventing and / or treating myocardial ischemia-reperfusion injury and / or health care.

6. The product for myocardial ischemia-reperfusion injury according to claim 5, characterized in that: It also contains pharmaceutical excipients, and / or health care product excipients, and / or medical excipients.

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