CN117752767A - A polypeptide composition derived from eggshell and its application in treating cardiovascular disease - Google Patents
A polypeptide composition derived from eggshell and its application in treating cardiovascular disease Download PDFInfo
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Abstract
The invention relates to a polypeptide composition derived from eggshell and application thereof in treating cardiovascular diseases, wherein the polypeptide composition consists of two compounds, namely, twenty-one peptide and twenty-two peptide extracted from eggshell membrane, and polypeptide sequences of the two compounds are ARGNTESQMKKVLHFDSITGA and ARGNTESQMKKVLHFDSITGAG respectively. The polypeptide composition can be directly absorbed and utilized by small intestine without being digested by human body, has high absorption speed and high bioavailability, can effectively inhibit myocardial inflammatory reaction induced by acute myocardial infarction, lighten inflammatory injury of myocardial cells, improve heart failure and arrhythmia symptoms, regulate human body blood lipid level and reduce the disease risk of atherosclerosis.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to a polypeptide composition derived from eggshell and application thereof in treatment of cardiovascular diseases.
Background
Cardiovascular diseases are common high-incidence diseases, the incidence rate and the death rate of the diseases are in an increasing trend year by year in recent years, the number of deaths caused by the cardiovascular diseases in the world exceeds 1500 ten thousand people each year, and the statistics of the health organization in the world predicts that the number of deaths caused by the cardiovascular diseases will be increased by 20% each year on the basis of the prior art in 2025. Cardiovascular diseases mainly comprise clinical symptoms such as atherosclerosis, acute myocardial infarction, arrhythmia, heart failure and the like. When the level of Triglyceride (TG), total Cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in human serum is increased and the level of high-density lipoprotein cholesterol (HDL-C) is decreased, excessive blood lipid levels are extremely liable to cause atherosclerosis of coronary arteries, thereby inducing the occurrence of acute myocardial infarction. The myocardial persistent ischemia and hypoxia caused by acute myocardial infarction causes the continuous rise of serum creatine kinase isoenzyme (CK-MB) level, the enhanced expression of cell inflammatory factors TNF-alpha and IL-6, and causes the heart inflammatory reaction, induces the myocardial cells and the interstitial structure to change, and causes the myocardial cell injury. Simultaneously, heart muscle functions decline, heart function indexes such as ejection fraction (LVEF), stroke Volume (SV), cardiac Output (CO) and the like decline, and a series of arrhythmia symptoms such as ventricular premature beat (VP), ventricular Tachycardia (VT), ventricular Fibrillation (VF) and the like are accompanied, so that the life safety of a patient is seriously threatened.
The eggshell membrane is a fibrous membrane between eggshells and egg white, is also called as a 'membrana Follicularis ovi', is a traditional Chinese medicinal material with long use history in China, and comprises about 4% -5% of the total weight of the eggshells, more than 90% of the eggshells are composed of proteins, and besides various protein substances such as keratin, collagen, ovalbumin and the like, the eggshell membrane is rich in various amino acids, and has wide clinical application in skin burn and scald repair, dermatitis tinea caused by immune system diseases, refractory pneumonia and other diseases. However, the shell membrane protein has a large number of disulfide bonds, so that the shell membrane protein has poor solubility, is not easy to decompose by gastric acid, has low bioavailability, and limits further development and utilization of the shell membrane protein.
ARGNTESQMKKVLHFDSITGA and ARGNTESQMKKVLHFDSITGAG are twenty-one peptide and twenty-two peptide compounds extracted from eggshell membrane, and the polypeptide compounds can be directly absorbed and utilized by small intestine without being digested by human body after oral administration, have high absorption speed and high bioavailability, can effectively reduce the levels of CK-MB, TNF-alpha and IL-6 in serum, relieve myocardial cell inflammation injury and apoptosis caused by acute myocardial infarction, protect myocardial cells, improve cardiac function level, improve heart failure and arrhythmia symptoms, and improve HDL-C content by reducing TG, TC, LDL-C level in serum, effectively reduce blood lipid level in human body and prevent atherosclerosis lesion.
Disclosure of Invention
The invention discloses a polypeptide composition derived from eggshell and application thereof in treating cardiovascular diseases, wherein the polypeptide composition consists of twenty-one peptide and twenty-two peptide compounds extracted from eggshell, namely eggshell membrane.
In the present invention, the polypeptide sequences of the twenty-one peptide and twenty-two peptide compounds comprising the composition are ARGNTESQMKKVLHFDSITGA and ARGNTESQMKKVLHFDSITGAG, respectively.
The polypeptide composition disclosed by the invention can inhibit the expression of TNF-alpha and IL-6 in serum, reduce the level of CK-MB in vivo, inhibit the occurrence of myocardial inflammatory reaction and relieve myocardial injury caused by acute myocardial infarction.
Meanwhile, the polypeptide composition can effectively relieve heart failure symptoms such as heart ejection fraction (LVEF), stroke Volume (SV), heart output (CO) decline and the like.
The polypeptide composition disclosed in the patent can effectively improve a series of arrhythmia symptoms such as ventricular premature beat (VP), ventricular Tachycardia (VT), ventricular Fibrillation (VF) and the like.
In addition, the polypeptide composition can also be used for reducing the risk of atherosclerosis by reducing Triglyceride (TG), total Cholesterol (TC), low density lipoprotein cholesterol (LDL-C) level in serum, increasing high density lipoprotein cholesterol (HDL-C) content, stabilizing blood lipid level.
The polypeptide composition can be prepared by extracting eggshell membrane, and can also be prepared by artificial synthesis.
The polypeptide compositions disclosed in the present invention may be used alone or in combination with other active substances.
Further, the polypeptide composition may be provided in any suitable form including, but not limited to, food products, special food products, pharmaceutical products, and the like.
Detailed Description
The present invention is specifically described by the following examples, which are provided for further illustration of the present invention and are not to be construed as limiting the scope of the present invention.
Example 1 experiment of Effect of polypeptide composition on myocardial injury in acute myocardial infarction rats
Establishment of experimental group and myocardial infarction rat model
After the selection of 60 SD rats and 2 weeks of adaptive feeding, the rats were randomly divided into 6 groups, namely a blank control group, a model group, a positive control rosuvastatin group and a polypeptide composition high, medium and low dose group, each group comprising 10 animals.
Model group, positive control group and polypeptide composition rats in each dosage group were intraperitoneally injected with 10% chloral hydrate solution
After anesthesia, the upper position is fixed, the trachea cannula is moved, a breathing machine (60 times/min, the tidal volume is 5mL/100 g) is connected, the left thoracic incision of the rat is performed, the pericardium is stripped, the heart is exposed, a 1.0 sterile silk thread is used for fastening at a position 1-2 mm away from the front descending start part of the left coronary artery, the coronary artery of the rat is blocked, and when the left ventricle below the fastening part appears local white, the myocardial infarction model of the rat is built. The blank control group directly sews the skin of the rat layer by layer without binding the left coronary artery after cutting the left thoracic cage of the rat.
Experimental administration
After the operation is finished for 1d, the positive control group rats are irrigated with rosuvastatin at a dose of 5mg/kg, and the high, medium and low dose groups (the weight ratio of the twenty-one peptide and the twenty-two peptide compounds in each dose group is 1:1) of the polypeptide composition are irrigated with stomach at doses of 300mg/kg, 200mg/kg and 100mg/kg respectively for 14d of continuous gastric irrigation. Rats in the blank group and the model group were perfused with an equal dose of physiological saline in the same manner.
Detection of CK-MB, TNF-alpha, IL-6 levels in rat serum
After the last gastric lavage is finished, 5mL of rat abdominal aortic blood is extracted, the blood is placed in a 3500r/min centrifuge for centrifugation for 20min, the upper serum is sucked, and the CK-MB, TNF-alpha and IL-6 levels in the serum are detected according to the ELISA kit.
The experimental results show that the levels of CK-MB, TNF-alpha and IL-6 in serum are increased to different degrees in the rats in the model group after ligation of the left coronary artery compared with the blank group. The levels of CK-MB, TNF-alpha and IL-6 in the serum of rats in the positive control group and the polypeptide composition in each dosage group were still higher than those in the blank control group, but were reduced compared with the model, wherein the level of the reduction in the high dosage group of the polypeptide composition was most remarkable. Experimental results show that the polypeptide composition can effectively reduce the levels of CK-MB, TNF-alpha and IL-6 in the serum of myocardial infarction rats, inhibit the occurrence of myocardial inflammatory reaction, protect myocardial cells and relieve myocardial injury of the rats caused by myocardial infarction.
TABLE 1 comparison of CK-MB, TNF-alpha, IL-6 levels in serum from groups of rats
Example 2 Experimental Effect of polypeptide composition on acute myocardial infarction-induced rat heart failure
Establishment of experimental group and model
After selecting 48 Wistar male rats and adaptively feeding for 2 weeks, the rats are randomly divided into 6 groups, namely a blank control group, a model group, a positive control losartan group and 8 polypeptide composition high, medium and low dose groups.
Model group, positive control group and polypeptide composition rats in each dosage group were intraperitoneally injected with 10% chloral hydrate solution
After anesthesia, the upper position is fixed, the trachea cannula is moved, a breathing machine (60 times/min, the tidal volume is 5mL/100 g) is connected, the left thoracic incision of the rat is performed, the pericardium is stripped, the heart is exposed, a 1.0 sterile silk thread is used for fastening at a position 1-2 mm away from the front descending start part of the left coronary artery, the coronary artery of the rat is blocked, and when the left ventricle below the fastening part appears local white, the myocardial infarction model of the rat is built. The blank control group directly sews the skin of the rat layer by layer without binding the left coronary artery after cutting the left thoracic cage of the rat.
Experimental administration
After the operation is finished for 1d, the positive control group rats are irrigated with losartan at a dosage of 40mg/kg, and the high, medium and low dosage groups (the weight ratio of the twenty-one peptide to the twenty-two peptide compound in each dosage group is 1:2) of the polypeptide composition are irrigated with stomach at dosages of 300mg/kg, 200mg/kg and 100mg/kg respectively for 21d of continuous gastric irrigation. Rats in the blank group and the model group were perfused with an equal dose of physiological saline in the same manner.
Rat heart function level detection
After 4 hours from the end of the last gastric lavage of the rat, 5% chloral hydrate is injected into the abdominal cavity to anesthetize the rat, four limbs of the rat are fixed in a supine position, the heart function of the rat is subjected to ultrasonic examination, and the average value of the heart function index Left Ventricular Ejection Fraction (LVEF), short axis shortening rate (LVFS), stroke Volume (SV) and Cardiac Output (CO) of the rat is detected and recorded in 5 cardiac cycles.
The experimental results show that compared with rats in a blank control group, the heart function indexes of rats in a model group such as ejection fraction, stroke volume and cardiac output are obviously reduced, and heart failure symptoms are shown. Compared with the rats in the model group, the three cardiac function indexes of the rats in each dosage group of the polypeptide composition are obviously improved, the cardiac function is improved, and obvious dose correlation is presented. Experimental results show that the complementary polypeptide composition can effectively enhance the myocardial function of rats and improve the heart failure condition.
Table 2 comparison of cardiac function indicators for rats of each group
Example 3 Experimental Effect of polypeptide composition on rat arrhythmia caused by acute myocardial infarction
Experimental grouping and model building
72 male SD rats were selected and subjected to adaptive breeding for 2 weeks, and then were randomly divided into 6 groups, namely a blank control group, a model group, a positive control lidocaine group and polypeptide composition high, medium and low dose groups, each group comprising 12 animals.
Model group, positive control group and polypeptide composition rats in each dosage group were intraperitoneally injected with 10% chloral hydrate solution
After anesthesia, the rat is fixed on the upper position, the trachea cannula is moved, a breathing machine (60 times/min, the tidal volume is 5mL/100 g) is connected, the left thoracotomy of the rat is performed, the pericardium is stripped, the heart is exposed, the rat is tightly tied at a position 1-2 mm away from the anterior descending initiation part of the left coronary artery by using a sterile thread of No. 1.0, the coronary artery of the rat is blocked, and when the left ventricle below the tied part appears local white, the model establishment is completed. The blank control group directly sews the skin of the rat layer by layer without binding the left coronary artery after cutting the left thoracic cage of the rat.
Experimental administration
Rats in the positive control group were perfused with lidocaine at a dose of 15mg/kg, and high, medium and low dose groups of the polypeptide composition (the weight ratio of the di-undecapeptide and the docosahexaenoic acid compound in each dose group was 2:1) were perfused with 300mg/kg, 200mg/kg and 100mg/kg, respectively, for 30 days. Rats in the blank group and the model group were perfused with an equal dose of physiological saline in the same manner.
Rat heart rhythm detection
After the end of the last gastric lavage for 2 hours, the symptoms of ventricular arrhythmia were induced by electric stimulation on each group of rats, and the occurrence time, duration and occurrence rate of the symptoms including ventricular premature beat (VP), ventricular Tachycardia (VT) and Ventricular Fibrillation (VF) of the rats were observed and recorded by an electrocardiogram.
Experimental results show that compared with a blank control group, arrhythmia symptoms such as ventricular premature beat, ventricular tachycardia and ventricular fibrillation are commonly generated in rats in the model group; compared with the model group, the positive control group and the polypeptide composition have obviously prolonged arrhythmia occurrence time of rats in each dosage group, obviously reduced duration and incidence of arrhythmia symptoms, and most obvious performance in the polypeptide composition high dosage group. Experimental results show that the polypeptide composition can effectively relieve arrhythmia symptoms such as ventricular premature beat, ventricular tachycardia and ventricular fibrillation.
TABLE 3 Effect of polypeptide compositions on rat arrhythmias
Example 4 Effect of polypeptide composition on rat blood lipid level experiment
Grouping and modeling
The 36 SD rats were randomly divided into 6 groups, each of which was a blank control group, a high-fat model group, a positive control simvastatin group, and high, medium, and low dose groups of the polypeptide composition, each group being 6 rats. The blank group was fed with normal feed, and the remaining groups of rats were fed with high cholesterol feed for 4 weeks, to establish a hyperlipidemic rat model.
Experimental administration
After successful molding, the positive control group was subjected to gastric lavage with simvastatin at a dose of 0.05g/kg, and the polypeptide composition was subjected to gastric lavage in high, medium and low dose groups (weight ratio of the di-undecapeptide and the docosahexaenoic acid peptide compound in each dose group is 1:1) at doses of 300mg/kg, 200mg/kg and 100mg/kg, respectively, 2 times daily, and continuous gastric lavage for 28d. Rats in the blank group and the model group were perfused with an equal dose of physiological saline in the same manner. During this period, the model group, the positive control group, and the polypeptide composition dose groups continued to be fed with high cholesterol diet. The blank group continued to be fed with normal feed.
8 hours after the end of the last lavage, each group of rats was anesthetized with 10% chloral hydrate. Blood is extracted from abdominal aorta to vacuum collection tube, and is centrifuged at 6000r/min for 20min, and upper serum is removed for refrigeration and measurement.
Blood lipid level detection in rat serum
Triglyceride (TG), total Cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels in rat serum were measured as described in ELISA kits.
The experimental result shows that compared with a blank control group, the serum level of TG, TC, LDL-C in the rats in the model group is obviously increased, and the HDL-C level is reduced; the level of TG, TC, LDL-C in the serum of rats in the positive control group and the polypeptide composition dose groups is still higher than that of the rats in the blank control group, but compared with the rats in the model group, the level of HDL-C is obviously reduced and obviously increased. Experimental results show that the polypeptide composition can effectively reduce TG, TC, LDL-C level in serum, improve HDL-C content, improve hyperlipidemia symptoms and reduce atherosclerosis disease risk.
TABLE 4 Effect of polypeptide compositions on rat blood lipid levels
Claims (9)
1. A polypeptide composition derived from eggshell and its use in the treatment of cardiovascular disease, characterized in that: the polypeptide composition consists of two compounds, namely, twenty-one peptide and twenty-two peptide extracted from eggshell membrane.
2. The polypeptide composition of claim 1, wherein: the polypeptide sequences of the twenty-one and twenty-two peptide compounds comprising the composition were ARGNTESQMKKVLHFDSITGA and ARGNTESQMKKVLHFDSITGAG, respectively.
3. Use of a polypeptide composition according to claim 1, characterized in that: the polypeptide composition can inhibit expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), reduce creatine kinase isoenzyme (CK-MB) level in vivo, inhibit myocardial inflammatory reaction, and relieve myocardial injury caused by acute myocardial infarction.
4. Use of a polypeptide composition according to claim 1, characterized in that: the polypeptide composition can improve heart failure symptoms such as heart ejection fraction (LVEF), stroke Volume (SV), and heart output (CO) decrease caused by acute myocardial infarction.
5. Use of a polypeptide composition according to claim 1, characterized in that: the polypeptide composition can improve arrhythmia symptoms such as ventricular premature beat (VP), ventricular Tachycardia (VT), ventricular Fibrillation (VF) and the like caused by acute myocardial infarction.
6. Use of a polypeptide composition according to claim 1, characterized in that: the polypeptide composition can reduce the risk of atherosclerosis by lowering Triglyceride (TG), total Cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels in serum, increasing high density lipoprotein cholesterol (HDL-C) levels, regulating blood lipid levels.
7. The polypeptide composition of claim 1, wherein: the polypeptide composition can be prepared by extracting eggshell membrane, and can also be prepared by artificial synthesis.
8. The polypeptide composition of claim 1, wherein: the polypeptide compositions may be used alone or in combination with other active substances.
9. The polypeptide composition of claim 8, wherein: the polypeptide composition may be provided in any suitable form including, but not limited to, food products, special food products, pharmaceutical products, and the like.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211175618.2A CN117752767A (en) | 2022-09-26 | 2022-09-26 | A polypeptide composition derived from eggshell and its application in treating cardiovascular disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211175618.2A CN117752767A (en) | 2022-09-26 | 2022-09-26 | A polypeptide composition derived from eggshell and its application in treating cardiovascular disease |
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| Publication Number | Publication Date |
|---|---|
| CN117752767A true CN117752767A (en) | 2024-03-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211175618.2A Pending CN117752767A (en) | 2022-09-26 | 2022-09-26 | A polypeptide composition derived from eggshell and its application in treating cardiovascular disease |
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| Country | Link |
|---|---|
| CN (1) | CN117752767A (en) |
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2022
- 2022-09-26 CN CN202211175618.2A patent/CN117752767A/en active Pending
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