阅读说明：本技术 一种防治心肌缺血后心功能衰竭的药物及其应用 (Medicine for preventing and treating heart failure after myocardial ischemia and application thereof ) 是由 陈维倩 周文静 丁靓 沈振亚 于 2021-08-23 设计创作，主要内容包括：本发明公开了一种防治心肌缺血后心功能衰竭的药物及其应用,具体为葡萄糖胺在制备心梗防治药物中的应用,动物实验证实,注射葡萄糖胺后,葡萄糖胺改善心梗后心功能、减缓心梗后心室扩张、减小心梗面积。(The invention discloses a medicine for preventing and treating myocardial ischemia-induced heart failure and application thereof, in particular to application of glucosamine in preparation of a myocardial infarction prevention and treatment medicine.)

1. Application of glucosamine in preparation of medicine or health product for preventing and treating heart failure after myocardial ischemia is provided.

2. The use according to claim 1, wherein the pharmaceutical or nutraceutical is an injectable formulation.

3. The use according to claim 1, wherein glucosamine is administered in an amount of 100 to 500 mg/kg/day.

4. Application of glucosamine in preparing medicine for improving myocardial function or slowing ventricular dilatation after myocardial infarction is provided.

5. The use according to claim 4, wherein the medicament is an injectable formulation.

6. Use of glucosamine in the manufacture of a medicament for reducing the area of myocardial infarction.

7. The use according to claim 6, wherein the medicament is an injectable formulation.

8. Application of glucosamine in preparing medicines or health products for preventing and treating myocardial infarction is provided.

9. The use of claim 8, wherein glucosamine improves post-infarct cardiac function, slows post-infarct ventricular dilation, and reduces infarct area.

10. The use according to claim 8, wherein the pharmaceutical or nutraceutical product is an injectable product.

Technical Field

The invention belongs to the medicine technology, relates to a medicine for preventing and treating heart failure after myocardial ischemia and application thereof, and particularly relates to application of glucosamine in preparation of a myocardial infarction prevention and treatment medicine.

Background

Myocardial Infarction (MI) is a cardiovascular disease seriously harming human health, and the incidence of ischemic Myocardial Infarction is continuously increased along with the continuous improvement of living standard of people in China. Ischemic myocardial infarction can lead to myocardial cell necrosis and scarring, which in turn affects cardiac function. Most of the current medicines or apparatus treatments can only relieve symptoms, but can not reverse the damage of heart tissues. Although heart transplantation can completely improve the heart condition, the heart transplantation is difficult to be widely applied clinically due to factors such as donor source scarcity, immunological rejection, expensive treatment cost and the like. Most of the current clinical application methods are reperfusion therapy, and because the adult heart has almost no regenerative function, the prognosis of patients is poor, and the left ventricle still has dysfunction. Therefore, the search for new strategies for improving the repair of injury after myocardial infarction is a problem to be solved urgently.

Glucosamine (glcne) is an amino-containing sugar in the human body, widely present in articular cartilage and connective tissue, and is an essential component of cartilage matrix and synovial fluid. Glucosamine has been used in europe for more than twenty years as an over-the-counter drug for the treatment of osteoarthritis, and no significant side effects have been observed with long-term use. Glucosamine has been approved by various countries as a dietary supplement for relieving arthritis, but no research report on the prevention and treatment of myocardial infarction by glucosamine has been found so far.

Disclosure of Invention

The invention discloses a new application of improving the function of the posterior heart of myocardial infarction by utilizing GlcN. The invention discloses that glucosamine may have a certain treatment effect on myocardial infarction. Exciting, preliminary experimental results have shown that the glucosamine control group not only recovers better cardiac function after myocardial infarction, suggesting that glucosamine has certain myocardial infarction control effect.

The invention adopts the following technical scheme:

a medicine for preventing and treating cardiac failure after myocardial ischemia contains glucosamine as active component.

The application of glucosamine in preparing medicine or health product for preventing and treating cardiac failure after myocardial ischemia; or the application of glucosamine in preparing medicines or health products for preventing and treating myocardial infarction.

The invention relates to application of GlcN in preparation of a drug or health product for preventing and treating myocardial infarction, in particular to application of GlcN in preparation of a drug, health product or food for protecting myocardial infarction, and realizes the technical effects of improving myocardial function after myocardial infarction, slowing down ventricular dilatation after myocardial infarction and reducing myocardial infarction area by glucosamine. Myocardial infarction is heart failure after myocardial ischemia.

The specific administration mode of the prepared drug disclosed by the invention can adopt intraperitoneal injection and the like, and in animal experiments, the administration amount of glucosamine is 100-500 mg/kg/day, preferably 200-400 mg/kg/day, such as 300 mg/kg/day.

The invention selects about 25g of C57BL/6J male mice as experimental objects, adopts a left coronary artery anterior descending ligation method to manufacture the myocardial infarction model, and the experiment meets the statistical requirements. After the abdominal cavity injection anesthesia, the patient is intubated through an oral trachea, and then connected with an air respirator, the breathing frequency is 110 times/min, the tidal volume is 3ml, and the respiratory suction ratio is 1: 1.3. In the right lateral position, the lateral skin of the left chest is incised through the left longitudinal incision, the pectoralis major is peeled off, the chest is opened through the third and fourth intercostal transverse incisions, the heart is exposed, and the pericardium is torn open through forceps. The left coronary artery was visualized by a surgical microscope. Ligating an anterior descending coronary artery (LAD) and a small amount of myocardial tissue at a position of 1-2 mm below the lower edge of the left auricle, wherein the depth of the needle insertion is about 1 mm, and the width is controlled within 3 mm. Closing the chest layer by layer. After ligation, the white part from the ligation part to the apex of the heart can be seen by naked eyes, and the successful establishment of the myocardial infarction model is proved.

Anesthetizing a mouse, placing a probe of a cardiac ultrasonic diagnostic apparatus on the anterior wall of a heart, taking a left ventricular two-dimensional short axis view at the level of papillary muscles, simultaneously recording M-type scanning, continuously measuring a left ventricular Ejection Fraction (EF), a shortened Fraction (FS), a left ventricular diastolic end diameter (LVEDD) and a left ventricular systolic end diameter (LVESD) in 3 cardiac cycles, detecting the cardiac function after the myocardial infarction, and obviously improving the cardiac function, ejection fraction and short axis shortening rate after the myocardial infarction by glucosamine; mice were sacrificed 56 days post-surgery and mouse Body Weight (BW), Heart Weight (HW), Tibia Length (TL) were measured; HW/BW and HW/TL are calculated, and the degree of cardiac dilatation of the GlcN control group is relatively small; mice were sacrificed after surgery, left ventricular tissue was stained for cardiac tissue, the effect of treatment was observed, and the results were visualized by conventional Masson staining procedure, observed under a common optical microscope and photographed. Analyzing the area of each part by adopting Image analysis software Image J, and calculating the myocardial infarction area/heart area; the infarct size of each group after myocardial infarction was observed by Masson staining for 56 days, and glucosamine was found to be effective in reducing the infarct size.

Myocardial infarction is a cardiovascular disease seriously harming human health, and the incidence of ischemic myocardial infarction is continuously increased along with the continuous improvement of living standard of Chinese people. The invention discloses glucosamine which can improve the cardiac function after myocardial infarction and reduce the myocardial infarction area, thereby preventing and treating myocardial infarction.

Drawings

FIG. 1 is a graphical representation of echocardiography measurements taken 28 days after myocardial infarction;

FIG. 2 is a graph of heart relative weight assessed in HW/BW and HW/TL 56 days post myocardial infarction;

FIG. 3 is the general view of the heart 56 days after myocardial infarction

FIG. 4 shows myocardial infarction areas of each group analyzed by Masson staining 56 days after myocardial infarction.

Detailed Description

The following examples are presented only to assist those skilled in the art in a more complete understanding of the present invention, and are not intended to limit the invention in any way. The specific experimental method and the testing method are conventional technologies, and the experimental group and the control group are parallel experiments.

The main materials and sources used were as follows:

c57BL/6J mice (provided by the sho-derived new drug research center, su, this experiment was approved by the ethical committee of the university of su); small animal ventilators (shanghai alcote biotechnology limited); small animal ultrasound imaging system (Visual sonic Vevo 2100); glucosamine (Sigma, USA) was dissolved in physiological saline (75 mg/mL).

Establishment of mouse myocardial infarction model

About 25g of C57BL/6J male mice are selected as experimental objects, and a left coronary artery anterior descending ligation method is adopted to prepare a myocardial infarction model. After the abdominal cavity injection anesthesia, the patient is intubated through an oral trachea, and then connected with an air respirator, the breathing frequency is 110 times/min, the tidal volume is 3ml, and the respiratory suction ratio is 1: 1.3. In the right lateral position, the lateral skin of the left chest is incised through the left longitudinal incision, the pectoralis major is peeled off, the chest is opened through the third and fourth intercostal transverse incisions, the heart is exposed, and the pericardium is torn open through forceps. The left coronary artery was visualized by a surgical microscope. Ligating the anterior descending coronary artery (LAD) and a small amount of myocardial tissue at the position of about 1.5mm below the lower edge of the left auricle, wherein the depth of the needle insertion is about 1 mm, and the width is controlled within 3 mm; closing the chest layer by layer. The ligation site becomes white to the apex of the heart after ligation, which proves the success of the myocardial infarction model.

Mice in the experimental group (control group, GlcN/P) were injected intraperitoneally with glucosamine (300 mg/kg/day) from one day before to 7 days after the myocardial infarction; control mice were injected with an equal amount of sterile saline as a control. Feeding in the same manner, and detecting the cardiac function and cardiac peduncle area after the cardiac peduncle.

Example 1 GlcN is effective in improving myocardial posterior function

Heart ultrasonic testing myocardial infarction posterior cardiac function

Mouse anaesthetizing (same method as before), after depilation, left lateral decubitus, placing the probe of heart ultrasonic diagnostic apparatus on the heart anterior wall, taking the left ventricle two-dimensional short axis view in the papillary muscle level, recording M-type scanning, and measuring left ventricle Ejection Fraction (EF) and shortening Fraction (FS) continuously for 3 cardiac cycles.

The experimental results are as follows: cardiac function was measured 28 days after myocardial infarction, and the GlcN control group significantly improved myocardial function after myocardial infarction (fig. 1A), ejection fraction (fig. 1B) and short axis shortening rate (fig. 1C). *P < 0.05，**P < 0.01。

Example 2: GlcN effectively slows post-myocardial ventricular dilatation

Mice were sacrificed 56 days post-surgery and mouse Body Weight (BW), Heart Weight (HW), Tibia Length (TL) were measured; HW/BW (FIG. 2A) and HW/TL (FIG. 2B) are calculated. The experimental results are as follows: the degree of cardiac dilation in the GlcN control group was relatively small (fig. 2); p < 0.05.

Example 3: GlcN effectively reduces myocardial infarct area

Masson staining: mice were sacrificed 56 days after surgery, left ventricular tissue was taken for cardiac tissue staining and the treatment effect was observed. The staining procedure was performed according to conventional Masson, and observed and photographed under a normal light microscope. And analyzing the area of each part by adopting Image analysis software Image J, and calculating the myocardial infarction area/heart area. The experimental results are as follows: overall view of heart (fig. 3), myocardial infarction and section position (fig. 4A), 56-day myocardial infarction surface (fig. 4B) and infarct size (fig. 4C) after each group of myocardial infarction were observed with Masson staining, and it was found that GlcN control group significantly reduced myocardial infarction area; p < 0.05.

The results of the above experiments comprehensively prove that: GlcN can effectively improve the posterior cardiac function of the myocardial infarction and reduce the area of the myocardial infarction, thereby preventing and treating the myocardial infarction.

Comparative example 12 Effect of DG on myocardial infarction

2-deoxy-D-glucose (2-DG) is a glucose analog which replaces the glucosamine in the experimental group and the same animal experiment (300 mg/kg/day) is carried out; mice were sacrificed 56 days after surgery, left ventricular tissue was taken for cardiac tissue staining and the treatment effect was observed. The staining procedure was performed according to conventional Masson, and observed and photographed under a normal light microscope. The area of each part is analyzed by adopting Image analysis software Image J, the myocardial infarction area/heart area is calculated, and the experimental result shows that the myocardial infarction area ratio of the 2-DG group is similar to that of the normal saline control group, and no difference exists.

The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.