CN113893242A - Use of ASH in myocardial protection - Google Patents
Use of ASH in myocardial protection Download PDFInfo
- Publication number
- CN113893242A CN113893242A CN202111184453.0A CN202111184453A CN113893242A CN 113893242 A CN113893242 A CN 113893242A CN 202111184453 A CN202111184453 A CN 202111184453A CN 113893242 A CN113893242 A CN 113893242A
- Authority
- CN
- China
- Prior art keywords
- ash
- group
- myocardial
- myocardial infarction
- heart
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000002107 myocardial effect Effects 0.000 title claims abstract description 20
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 23
- 206010019280 Heart failures Diseases 0.000 claims description 18
- 230000004217 heart function Effects 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 8
- 206010016654 Fibrosis Diseases 0.000 claims description 7
- 230000004761 fibrosis Effects 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 208000031225 myocardial ischemia Diseases 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 208000009525 Myocarditis Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- -1 patch Substances 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 15
- 150000001875 compounds Chemical class 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 9
- 238000002474 experimental method Methods 0.000 abstract description 7
- 238000003860 storage Methods 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 19
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000010186 staining Methods 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 10
- 210000004351 coronary vessel Anatomy 0.000 description 7
- 239000012188 paraffin wax Substances 0.000 description 7
- TVTJZMHAIQQZTL-WATAJHSMSA-M sodium;(2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylate Chemical compound [Na+].C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C([O-])=O)CCCC1=CC=CC=C1 TVTJZMHAIQQZTL-WATAJHSMSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000010171 animal model Methods 0.000 description 4
- 230000000747 cardiac effect Effects 0.000 description 4
- 239000008399 tap water Substances 0.000 description 4
- 235000020679 tap water Nutrition 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229960001880 fosinopril sodium Drugs 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 210000005240 left ventricle Anatomy 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 2
- 206010028594 Myocardial fibrosis Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 241000218170 Coriaria Species 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000008828 contractile function Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 210000000876 intercostal muscle Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 210000000062 pectoralis major Anatomy 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000008143 steroidal glycosides Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000009461 vacuum packaging Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- XOSXWYQMOYSSKB-LDKJGXKFSA-L water blue Chemical compound CC1=CC(/C(\C(C=C2)=CC=C2NC(C=C2)=CC=C2S([O-])(=O)=O)=C(\C=C2)/C=C/C\2=N\C(C=C2)=CC=C2S([O-])(=O)=O)=CC(S(O)(=O)=O)=C1N.[Na+].[Na+] XOSXWYQMOYSSKB-LDKJGXKFSA-L 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention discloses an application of ASH in myocardial protection, belonging to the technical field of medicines, wherein the chemical structure of the ASH is shown in figure 1, pharmacological experiments on mice around myocardial infarction prove that the compound has the advantages of myocardial protection effect, obvious effect, good safety, simple and convenient medication, low price and easy obtainment of raw materials, and convenient transportation and storage, and the compound has wide application prospect as a myocardial protection medicine.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a compound in myocardial protection.
Background
Cardiovascular disease is the leading cause of death in the global population, and mortality is at the first of the disease and is still rising year by year, severely harming human health. When myocardial infarction occurs, myocardial ischemia and hypoxia cause infiltration of inflammatory cells such as macrophages and monocytes, local inflammatory reaction is induced, and then myocardial cell death is caused, so that cardiac dysfunction, myocardial remodeling and heart failure are caused. Heart Failure (HF) is called Heart failure for short, is a must-pass stage of various cardiovascular diseases such as coronary Heart disease, hypertension, myocarditis and the like, and is a worldwide medical and health problem. Heart failure is a disorder of cardiac insufficiency, generally manifested by a reduced or impaired myocardial contractile function, resulting in a reduced cardiac output and a reduced blood supply of oxygen and metabolism to the body tissues, which leads to failure of cardiac function. The cardiovascular disease prevalence rate in China is in a continuously rising stage, the mortality rate is far higher than that in countries such as Europe and America, patients with cardiovascular disease in China are about 2.9 hundred million, and the number of patients with heart failure is 450 million.
Clinically, the drugs for resisting heart failure are mainly classified into renin-angiotensin system inhibitors, aldosterone inhibitors, diuretics, beta receptor blockers, cardiac glycosides and the like, but all of them have serious adverse reactions, such as dyspnea, heart rate slowing, blood pressure lowering, electrolyte disturbance and the like. Therefore, the search for safe and effective anti-heart failure drugs has important significance for the treatment of clinical cardiovascular and cerebrovascular diseases.
Chinese patent 2019109751780 discloses a compound having the following structure,
the specification discloses that the compound has an anticoagulant effect, but does not disclose that the compound has an anti-heart failure effect or a myocardial protection effect, and the inventor establishes a myocardial ischemia model by ligating the left anterior descending branch of the coronary artery of a mouse in the process of pharmacodynamic study, and unexpectedly discovers that the compound has a protection effect on experimental ischemic cardiomyopathy mice and can be used for treating ischemic cardiomyopathy.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a novel myocardial protection compound and application thereof. The technical problem to be solved by the invention is to provide the myocardial protection compound which has obvious myocardial protection effect, good safety, simple and convenient medication, low price and convenient transportation and storage.
The invention achieves the above objects by the following technical scheme, and provides a compound, the structural formula of which is as follows:
herein named: ASH
The compound has the molecular formula: C13H16O5, molecular weight 252.27. This compound has been disclosed in the specification of the chinese patent.
The invention unexpectedly discovers that the compound ASH has the myocardial protection effect, and therefore, the invention provides the application of the ASH in preparing the myocardial protection medicament.
The application of the invention is characterized by comprising the protection of myocardial damage caused by any one reason, such as: myocarditis, myocardial ischemia, arrhythmia, heart failure, myocardial infarction, cardiac insufficiency, etc.
The use according to the invention, characterized in that the use is an ASH that can be used for the prevention and treatment of heart failure.
The use according to the invention is characterized in that ASH can be used for the prevention and treatment of heart failure caused by myocardial infarction.
The application is characterized in that the ASH can improve the cardiac function and reduce the weight ratio of heart to weight and the increase of fibrosis area caused by myocardial infarction.
The application of the invention is characterized in that the medicine is prepared into any medicine dosage form for taking by taking ASH as a medicine active ingredient.
The use of the present invention is characterized in that, wherein the pharmaceutical dosage form is selected from: oral preparation, injection, patch, and suppository.
The use of the present invention is characterized in that, wherein the pharmaceutical dosage form is selected from: oral preparation and injection.
The use of the present invention is characterized in that, wherein the pharmaceutical dosage form is selected from: can be made into injection.
The use of the present invention is characterized in that, wherein, the use comprises ASH or a pharmaceutically acceptable salt thereof. Preferably, the medicament is beneficial to the absorption of organisms and the improvement of the utilization rate of the medicament.
Compared with the prior art, the invention has the beneficial technical effects that:
(1) the myocardial protection effect is obvious: can obviously improve the cardiac function and the fibrosis area, and can be used as a safe and effective medicament for treating ischemic heart disease.
(2) The safety is good: the new myocardial protection compound has large tolerance amount and no obvious toxic or side effect.
(3) The medicine is simple and convenient to take, and is easy to be absorbed by human or animals when orally taken.
(4) Compared with other imported myocardial protection medicaments, the medicament provided by the invention is low in price, high in cost performance and easy to accept by patients.
(5) Is convenient for transportation and storage, sealed and placed in dry place.
Drawings
FIG. 1 shows the structure of ASH.
Figure 2 effect of ASH on cardiac function in myocardial infarction mice.
FIG. 3. effect of ASH on heart-to-weight ratio in myocardial infarction mice.
Figure 4 effect of ASH on fibrotic area in myocardial infarction mice.
Data are expressed as mean ± sem<0.001vs. sham-operated group,#P<0.05vs. myocardial infarction group,##P<0.01vs. myocardial infarction group,###P<0.001vs. myocardial infarction group. Sham group, n is 7; myocardial infarction group, n ═ 8; fosinopril sodium tablet group (40mg/kg), n is 5; ASH (10mg/kg), n ═ 10; ASH (20mg/kg), n-5, ASH (40mg/kg), n-5.
Detailed Description
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. The examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
And (3) testing: ASH myocardial preservation pharmacodynamic study
The purpose is as follows: the protective effect of ASH on myocardial infarction of mice is explored.
The method comprises the following steps: 18-22 g of SPF-grade C57BL/6 male mice are selected, and a myocardial infarction model is constructed by ligating the left anterior descending branch of the coronary artery, and is randomly divided into 6 groups, namely a pseudo-operation group (8), a myocardial infarction model group (11), an ASH low dose group (11), an ASH medium dose group (11), an ASH high dose group (11) and a fosinopril sodium group (10). After 3 days of establishing a myocardial infarction model, performing intragastric administration, and respectively administering a solvent with corresponding dose to a sham operation group and a model group and administering 10 mg/kg.d of ASH to animals with low, medium and high ASH doses-1、20mg/kg.d-1、40mg/kg.d-1The dose of fosinopril sodium group is 40mg/kg-1. After 28 days of gastric lavage, cardiac function of each group of mice is detected by cardiac ultrasound, heart weight and body weight are weighed, heart-to-body weight ratio is calculated, and degree of myocardial fibrosis is detected by coriaria staining.
1. Purpose of experiment
A myocardial infarction mouse model can be established by ligating the left anterior descending branch of the coronary artery of a mouse, and then a test drug is given to the mouse to judge the effect of the test drug on the heart function, the heart-weight ratio and the fibrosis of the myocardial infarction mouse.
2. Experimental medicine
2.1 test drugs
| Name (R) | Shape and physical and chemical properties | Storage conditions | Source |
| ASH | Orange-yellow oily liquid | At 4 ℃ in the absence of light |
2.2 Positive control
2.3 negative control and vehicle
Olive oil
3. Laboratory animals and laboratory environments
3.1 Experimental animals
C57BL/6 mice, SPF grade, male, total 62 animals, animal weight range: 18-22 g, wherein the initial weight of the animal is not more than or less than 20% of the average weight.
Animal sources: liaoning province experimental animal resource center.
Production unit license number: SYXK (Black) 2019-.
Receiving date: 2021-3-10
3.2 Experimental Environment
The mice are raised in laboratory animal rooms of a transformation center of Harbin medical university, the raising environment is a barrier system, the room temperature is 20-26 ℃, the humidity is 40-70%, the ventilation volume is 10-15 times/h of fresh air, and the illumination is 12 h.
3.3 feed and Drinking Water
Maintaining the feed to be clean feed of national standard, vacuum packaging, and storing at room temperature.
The feed source is as follows: beijing Huafukang Biotech GmbH Ltd
Animal feed production license number: jing Fei certificate (2014)06054
Drinking water: autoclaved purified water was supplied from drinking bottles, animals were allowed to drink water freely, changing water once a day.
4. Main reagent for detection
5. Main instrument for experiment
| Name (R) | Company(s) | Goods number |
| Ultrasonic instrument for small animal | VisualSonics | |
| Balance with a movable handle | Shimadzu of Japan | AUW120D |
| Centrifugal machine | HUNAN XIANGYI LABORATORY INSTRUMENTS DEVELOPMENT Co.,Ltd. | L500 |
| Electronic balance | German Sedolis group | BS 124S |
| High-speed refrigerated centrifuge | Hitachi of Japan | CF-16RXII |
| Paraffin waxSlicing machine | Thermo corporation of America |
6. Dose selection
ASH group:
ASH low dose group 10 mg/kg. d-1
ASH medium dosage group 20 mg/kg. d-1
ASH high dose group 40mg/kg. d-1
Fosinopril sodium tablet group: 40mg/kg. d-1
7. Methods and frequencies of administration
Gavage administration, 1 time/day
8. Procedure of experiment
8.1 animal receiving and quarantine
C57BL/6 mice, males, were introduced prior to the official experiment. All animals were quarantined and acclimated for one week, with one check for body weight at each time during introduction and quarantine. Qualified animals enter formal experiments according to the conditions of weight increase, general physical signs, activities and the like of the animals in the adaptation period.
8.2 myocardial infarction model establishment
A mouse myocardial ischemia model is established by ligating the left anterior descending branch of the mouse coronary artery. Healthy male C57BL/6 mice (20. + -.2 g) were anesthetized by intraperitoneal injection with afatin (0.2g/kg), and the anesthetized mice were fixed on a mouse console in the supine position and connected to a ventilator. Making a left upper oblique incision to a right lower oblique incision on the skin of a left chest, wherein the incision is about 1.5-2.0 cm, separating pectoralis major and anterior serratus, separating intercostal muscles at the 4 th and 5 th intercostal blunt, slightly pushing out the heart, threading an 7/0 ligature at the position 1-2 mm from the lower edge of a left auricle of the anterior descending branch of the left coronary artery, performing ligature on the left anterior descending branch of the coronary artery, and after ligature, showing that the color of the apex of the heart becomes white, and showing that an obvious S-T section in electrocardiogram is lifted.
8.3 administration and moulding period:
the mice of SPF grade C57BL/6 after adaptive feeding are randomly weighed and randomly divided into 6 groups, namely a sham operation group, a myocardial infarction model group, an ASH low dose group, an ASH medium dose group, an ASH high dose group and a fosinopril sodium group, after the model is built, ASH, fosinopril sodium tablets and a blank solvent are given through intragastric gavage, the intragastric gavage is continuously carried out for 28 days, the heart function of each group of mice is detected on the 28 th day, materials are taken, and the heart-weight ratio and the fibrosis area are counted.
9. Frequency and method for checking index and measurement
9.1 general observations
General clinical observations were made once daily during the course of the experiment. The appearance, spirit and movement of the mice after administration were observed. If some animals die or are dying, the animals are examined timely to know the cause of death, and the death number is recorded.
The general state of each group of mice is more normal.
9.2 weight detection
Each mouse was weighed once a week on an electronic balance.
9.3 mouse cardiac function assay
Detection of cardiac hemodynamic parameters in mice
A 2100 high-resolution small animal ultrasonic imaging system and a MicroScan MS 250-. Removing hair at chest area, and applying ultrasonic gel. The probe is placed in front of the left chest of a mouse, 2D ultrasound displays a left ventricle long axis section, M-mode ultrasound is taken under two-dimensional (2D) guidance to record the motion condition of the left ventricle, and Ejection Fraction (EF) and short axis shortening rate (FS) are measured, so that the left ventricle function of each group of animals is evaluated according to the index.
9.4 mouse Heart weight ratio determination
Each group of mice was collected, the abdominal cavity was opened, and the heart was washed with physiological saline. The excess tissue was cut off, and the residual physiological saline was blotted with filter paper and weighed.
9.5 mouse Heart fibrosis area determination
(1) Preparation of Paraffin section samples
The mice were anesthetized as described above, and the intact hearts of the mice after establishment of the ischemia reperfusion model were placed in 4% paraformaldehyde solution. After the tissue block was fixed for 24 hours, the tissue with the lesion site was placed in a tissue embedding cassette, transected along the longitudinal axis of the heart, and dehydrated in an automatic dehydrator. After 20 hours, the tissue mass was removed. Paraffin was melted and the tissue blocks were embedded using an automatic embedding machine. When preparing the sample, the tissue wax block is vertically fixed on a machine, the blade is fixed, a paraffin section of 4 mu m/piece is prepared, the paraffin section is put into warm water to remove wrinkles, the paraffin section is flatly attached on a glass slide, and the paraffin section is used after being dried in an oven at 55 ℃ overnight.
(2) Masson staining
The tissue slices were deparaffinized in a basket, immersed in xylene solution, the solution covered the tissue, immersed twice, each for 5 minutes, and then sequentially immersed in absolute ethanol, 95% ethanol, 80% ethanol, 70% ethanol for 2 minutes each. After dewaxing was complete, the samples were soaked in distilled water for 2 minutes. The staining in hematoxylin is carried out for 10 minutes, then the staining is carried out for 10 minutes by tap water, then the staining is carried out for 10 minutes by British red solution, then the staining is carried out for 1 minute by tap water, the staining is carried out for 15 minutes by phosphomolybdic acid and phosphotungstic acid mixed solution, the staining is carried out for 10 minutes by aniline blue solution, then the staining is carried out for 1 minute by tap water, and the staining is carried out for 4 minutes by acetic acid solution, then the staining is carried out for 30 seconds by tap water. And finally, dehydrating, sequentially putting the materials into 95% ethanol, 100% ethanol, xylene I and xylene II, soaking for 5 minutes respectively, sealing the cover glass with neutral resin, and observing by using an optical microscope after the cover glass is dried.
10. Conclusion
As shown in fig. 2, 28 days after the ligation of left anterior descending coronary artery in mice, the Ejection Fraction (EF) and the minor axis shortening rate (FS) were significantly decreased in the myocardial infarction group compared to the sham group (P <0.001vs. sham group), while the ASH group reversed the above phenomenon (# P <0.05vs. myocardial infarction group). As shown in fig. 3, the myocardial infarction model group showed an increase in the heart-weight ratio (P <0.001vs. sham) compared to the sham group, and ASH decreased the increase in the heart-weight ratio of mice induced by myocardial infarction (# P <0.05vs. myocardial infarction group, # P <0.01vs. myocardial infarction group, # P <0.001vs. myocardial infarction group). As shown in fig. 4, the myocardial fibrosis area was significantly increased in the myocardial infarction model group compared to the sham group (# # P <0.001vs. sham), while ASH decreased the increase in the mouse fibrosis area caused by myocardial infarction (# # P <0.001vs. myocardial infarction group).
Claims (10)
- Use of an ASH in the manufacture of a myocardial preservation medicament, the ASH having the structure:
- 2. the use according to claim 1, wherein the use is that ASH can be used for the prevention and treatment of the following diseases: myocarditis, myocardial ischemia, arrhythmia, heart failure, myocardial infarction, cardiac insufficiency.
- 3. The use according to claim 2, wherein the use is ASH that can be used for the prevention and treatment of heart failure.
- 4. The use according to claim 2, wherein the use is for the prevention and treatment of heart failure caused by myocardial infarction by ASH.
- 5. The use according to claim 2, wherein the use is for improving cardiac function and reducing the increase in weight ratio of heart to weight and area of fibrosis due to myocardial infarction in ASH.
- 6. The use of claim 1, wherein the medicament is prepared from ASH as a pharmaceutically active ingredient in any one of the pharmaceutical dosage forms for administration.
- 7. The use of claim 1, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation, injection, patch, and suppository.
- 8. The use of claim 7, wherein the pharmaceutical dosage form is selected from the group consisting of: oral preparation and injection.
- 9. The use of claim 8, wherein the pharmaceutical dosage form is selected from the group consisting of: can be made into injection.
- 10. The use according to claim 1, wherein the use comprises ASH or a pharmaceutically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111184453.0A CN113893242B (en) | 2021-10-12 | 2021-10-12 | Use of ASH in myocardial protection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111184453.0A CN113893242B (en) | 2021-10-12 | 2021-10-12 | Use of ASH in myocardial protection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113893242A true CN113893242A (en) | 2022-01-07 |
| CN113893242B CN113893242B (en) | 2023-10-13 |
Family
ID=79191433
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111184453.0A Active CN113893242B (en) | 2021-10-12 | 2021-10-12 | Use of ASH in myocardial protection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113893242B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116602966A (en) * | 2023-05-11 | 2023-08-18 | 华宝民康(广东)医药集团有限公司 | Application of 13-methyl-palmatine in preparation of medicines for resisting myocardial ischemia injury and heart fibrosis |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT9021075A0 (en) * | 1990-07-26 | 1990-07-26 | Italfarmaco Spa | NEW BENZOIC ACIDS DERIVATIVES SUBSTITUTED FOR CARDIOVASCULAR ACTIVITY |
| WO2007054451A1 (en) * | 2005-11-11 | 2007-05-18 | Nicox S.A. | Use of combinations of nitric oxide-releasing aspirin and aspirin for the treatment of cardiovascular diseases |
| CN101811974A (en) * | 2010-04-15 | 2010-08-25 | 合肥医工医药有限公司 | 4-(3-(dimethoxy) propoxy)-3, 5-dimethoxy benzoic acid, and preparation method and medical purpose thereof |
| JP2010189418A (en) * | 2010-04-16 | 2010-09-02 | Inst Of Materia Medica Chinese Acadmy Of Medical Sciences | NEW 2-(alpha-HYDROXYPENTYL)BENZOATE, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
| CN103599547A (en) * | 2012-12-06 | 2014-02-26 | 河北医科大学 | Nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as preparation method and application thereof |
| CN110668947A (en) * | 2019-10-14 | 2020-01-10 | 新乡海盈生物科技有限责任公司 | O-hydroxybenzoic acid polyglycol ester compound and synthesis preparation method and medical application thereof |
-
2021
- 2021-10-12 CN CN202111184453.0A patent/CN113893242B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT9021075A0 (en) * | 1990-07-26 | 1990-07-26 | Italfarmaco Spa | NEW BENZOIC ACIDS DERIVATIVES SUBSTITUTED FOR CARDIOVASCULAR ACTIVITY |
| WO2007054451A1 (en) * | 2005-11-11 | 2007-05-18 | Nicox S.A. | Use of combinations of nitric oxide-releasing aspirin and aspirin for the treatment of cardiovascular diseases |
| CN101811974A (en) * | 2010-04-15 | 2010-08-25 | 合肥医工医药有限公司 | 4-(3-(dimethoxy) propoxy)-3, 5-dimethoxy benzoic acid, and preparation method and medical purpose thereof |
| JP2010189418A (en) * | 2010-04-16 | 2010-09-02 | Inst Of Materia Medica Chinese Acadmy Of Medical Sciences | NEW 2-(alpha-HYDROXYPENTYL)BENZOATE, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
| CN103599547A (en) * | 2012-12-06 | 2014-02-26 | 河北医科大学 | Nitric oxide donor type non-steroidal anti-inflammatory drug beta-cyclodextrin or beta-cyclodextrin derivative inclusion compound as well as preparation method and application thereof |
| CN110668947A (en) * | 2019-10-14 | 2020-01-10 | 新乡海盈生物科技有限责任公司 | O-hydroxybenzoic acid polyglycol ester compound and synthesis preparation method and medical application thereof |
Non-Patent Citations (1)
| Title |
|---|
| LIU C，等: ""3, 5-Dimethoxy-4-(3-(2-carbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4-guanidino-butyl ester: A novel twin drug that prevents primary cardiac myocytes from hypoxia-induced apoptosis"", 《 EUROPEAN JOURNAL OF PHARMACOLOGY》, vol. 700, no. 1, pages 118 - 126, XP028981063, DOI: 10.1016/j.ejphar.2012.11.028 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116602966A (en) * | 2023-05-11 | 2023-08-18 | 华宝民康(广东)医药集团有限公司 | Application of 13-methyl-palmatine in preparation of medicines for resisting myocardial ischemia injury and heart fibrosis |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113893242B (en) | 2023-10-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Benjamin et al. | Facial granuloma associated with Fusarium infection | |
| CN110172064B (en) | Flavone derivatives, preparation method and medical application thereof | |
| CN1762967B (en) | Enoxolone derivative, preparation method and uses | |
| CN113893242A (en) | Use of ASH in myocardial protection | |
| CN110876798A (en) | Application of caspofungin in preparation of medicine for treating ischemia/reperfusion injury | |
| CN102048727B (en) | Application of formononetin in preparing of medicament for restricting angiogenesis | |
| CN102516079B (en) | Synthetic method of novel ferulic acid derivative | |
| CN115192573B (en) | Application of demethyleneberberine hydrochloride in preparation of medicines for treating pulmonary fibrosis | |
| WO2020062780A1 (en) | Medicament for preventing and treating ischemic heart diseases or ischemic encephalopathy or thrombosis and use thereof | |
| JP2017524047A (en) | Yokuinin oil containing 13 kinds of glycerides, formulation and application | |
| CN102389434B (en) | Medicinal composition for treating ischemic cerebrovascular disease, and preparation method thereof | |
| CN110538170B (en) | Application of macamides compound or salt thereof in preparation of medicine for preventing or treating hepatic fibrosis diseases | |
| CN110511930B (en) | Sal-miR-58 and application thereof in inhibition of vascular inflammatory reaction and aneurysm formation | |
| CN108498546B (en) | Traditional Chinese medicine composition for preventing or treating ulcerative colitis canceration and application | |
| CN109134694B (en) | Sulfated derivative of dendrobium nobile polysaccharide and preparation method and application thereof | |
| CN114588212A (en) | New use of traditional Chinese medicine water lettuce for resisting heart failure | |
| CN111920871A (en) | Medicine for resisting myocardial ischemia reperfusion injury | |
| CN110237085A (en) | Pharmaceutical preparation and application thereof | |
| CN110237086A (en) | Composition, pharmaceutical preparation and purposes | |
| CN112773807B (en) | Medical application of composition composed of icariin and asiatic acid | |
| CN110051671B (en) | Application of purslane amide E in preparation of medicine for treating ischemic heart disease | |
| CN114652714B (en) | Application of macrolide in pancreatic cancer resistance | |
| CN112716939B (en) | Application of scopoletin in preparation of preparation for treating ischemic cardiovascular and cerebrovascular diseases | |
| CN112245582B (en) | Application of RAB22A gene as target in preparation of myocardial infarction treatment product and related product | |
| CN113143935A (en) | Application of stigmasterol in preparation of medicine for improving myocardial hypertrophy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |