CN111575363A - Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury - Google Patents
Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury Download PDFInfo
- Publication number
- CN111575363A CN111575363A CN202010377075.7A CN202010377075A CN111575363A CN 111575363 A CN111575363 A CN 111575363A CN 202010377075 A CN202010377075 A CN 202010377075A CN 111575363 A CN111575363 A CN 111575363A
- Authority
- CN
- China
- Prior art keywords
- group
- rat
- mir
- acute
- myocardial
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- 208000031225 myocardial ischemia Diseases 0.000 title claims abstract description 20
- 238000011160 research Methods 0.000 title claims abstract description 13
- 206010063837 Reperfusion injury Diseases 0.000 title claims abstract description 12
- 241000700159 Rattus Species 0.000 claims abstract description 50
- 230000014509 gene expression Effects 0.000 claims abstract description 28
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 26
- 230000010410 reperfusion Effects 0.000 claims abstract description 20
- 230000000694 effects Effects 0.000 claims abstract description 18
- 102100039996 Histone deacetylase 1 Human genes 0.000 claims abstract description 13
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 claims abstract description 13
- 238000002474 experimental method Methods 0.000 claims abstract description 13
- 230000006195 histone acetylation Effects 0.000 claims abstract description 13
- 230000002107 myocardial effect Effects 0.000 claims abstract description 11
- 230000001154 acute effect Effects 0.000 claims abstract description 10
- 230000009456 molecular mechanism Effects 0.000 claims abstract description 8
- 210000004351 coronary vessel Anatomy 0.000 claims abstract description 4
- 108091048308 miR-210 stem-loop Proteins 0.000 claims abstract 9
- 101000877681 Homo sapiens Forkhead box protein O3 Proteins 0.000 claims description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- 102100035421 Forkhead box protein O3 Human genes 0.000 claims description 16
- 208000028867 ischemia Diseases 0.000 claims description 13
- 230000008859 change Effects 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 230000006907 apoptotic process Effects 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 210000000683 abdominal cavity Anatomy 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000010186 staining Methods 0.000 claims description 6
- 206010003119 arrhythmia Diseases 0.000 claims description 5
- 230000006793 arrhythmia Effects 0.000 claims description 5
- 230000002018 overexpression Effects 0.000 claims description 5
- 239000005089 Luciferase Substances 0.000 claims description 4
- 108700008625 Reporter Genes Proteins 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000005516 engineering process Methods 0.000 claims description 3
- 230000000004 hemodynamic effect Effects 0.000 claims description 3
- 238000003364 immunohistochemistry Methods 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 238000003753 real-time PCR Methods 0.000 claims description 3
- 238000012216 screening Methods 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 abstract description 3
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 2
- 230000006718 epigenetic regulation Effects 0.000 abstract description 2
- 108091070501 miRNA Proteins 0.000 abstract description 2
- 239000002679 microRNA Substances 0.000 abstract description 2
- 230000003278 mimic effect Effects 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 3
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 230000001292 preischemic effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000007201 Myocardial reperfusion injury Diseases 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000004049 epigenetic modification Effects 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2871—Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
Abstract
The invention discloses a research method of MS-275 acting on acute myocardial ischemia reperfusion injury, which comprises the following steps: the method comprises the following steps: establishing an acute MI/RI model of the rat by performing anterior descending ligation on the left coronary artery of the SD male rat; step two: observing the effect of MS-275 in the MI/RI acute phase of rats; step three: the molecular mechanism of MS-275 on the protection of rat MI/RI was explored. The research achieves the following research purposes by establishing an acute MI/RI model of a rat and combining an internal experiment and an external experiment: 1) observing histone acetylation level, HDAC1 and microRNA-210(miR-210) expression in rat MI/RI acute-phase myocardial tissues; 2) MS-275, a novel HDACI type selective inhibitor, was demonstrated to have protective effects on rat MI/RI and its effects on histone acetylation level, HDAC1 and miR-210 expression in myocardial infarction area tissues after rat myocardial ischemia reperfusion; 3) the specific molecular mechanism of MS-275 for improving MI/RI of rats is revealed from the perspective of miRNA epigenetic regulation, and important theoretical and experimental basis is provided for treating MI/RI by HDACI.
Description
Technical Field
The invention relates to the technical field of medicine, in particular to a research method for acting on acute myocardial ischemia-reperfusion injury by MS-275.
Background
A large number of researches show that histone deacetylase is used as an important epigenetic modification regulatory factor and participates in the pathogenesis process of myocardial ischemia/reperfusion injury. The histone deacetylase inhibitor can interfere the function of HDACs, effectively reduce ischemia/reperfusion injury, and has a wide treatment prospect in the field of myocardial protection. However, the specific molecular mechanisms involved in this protective effect are less studied.
Disclosure of Invention
In order to overcome the problems, the invention provides a research method for the effect of MS-275 on acute myocardial ischemia-reperfusion injury.
The technical scheme adopted by the invention is as follows:
the research method of the effect of MS-275 on acute myocardial ischemia-reperfusion injury comprises the following steps:
the method comprises the following steps: establishing an acute MI/RI model of the rat by performing anterior descending ligation on the left coronary artery of the SD male rat;
step two: observing the effect of MS-275 in the MI/RI acute phase of rats;
step three: the molecular mechanism of MS-275 on the protection of rat MI/RI was explored.
Wherein, step one includes: SD male rats 72 were randomly divided into 4 groups of 18 per group: wherein the first group is a Sham group (Sham group) with only threading and no ligation; the second group was ischemic 30-minute group (I30 min group); the third group was a 30-minute ischemia reperfusion 60-minute group (I/R60min group); the fourth group was an ischemia 30-minute reperfusion 2-hour group (I/R120 min group); after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the expression change of HDAC1 and miR-210 are detected through technologies such as immunohistochemistry, histone acetylation detection kits, real-timePCR and the like.
Wherein, step two includes: SD male rats 90 were randomly divided into 3 groups of 30 per group: the first group is a Sham operation group (Sham group), which is not ligated by threading, and is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation, respectively; the second group is myocardial ischemia/reperfusion group (I/R group), which is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation respectively; the third group is myocardial ischemia/reperfusion + HDACI pretreatment group (I/R + MS-275 group), and MS-275(10mg/kg) was intraperitoneally injected 24 hours and 1 hour before the operation; ischemia/reperfusion time is 30min/120min, and hemodynamics and arrhythmia of rats in each group are monitored in the experimental process; after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the HDAC1 and the expression change of miR-210 are detected.
Wherein, step three includes: screening and identifying a downstream target gene FOXO3A of miR-210 by using methods such as bioinformatics, a dual-luciferase reporter gene system, interference over-expression and the like; MS-275 treats the H9c2 cell strain, and detects the level of miR-210 promoter zone protein H4ac, the expression of miR-210 and FOXO3A and the apoptosis condition before and after treatment; analyzing the correlation of miR-210 and FOXO3A expression in rat ischemia reperfusion myocardial infarction area tissues; the target gene resilience experiment proves that miR-210/FOXO3A mediates the myocardial protection effect of MS-275.
The invention has the following advantages:
the research achieves the following research purposes by establishing an acute MI/RI model of a rat and combining an internal experiment and an external experiment: 1) observing histone acetylation level, HDAC1 and microRNA-210(miR-210) expression in rat MI/RI acute-phase myocardial tissues; 2) MS-275, a novel HDACI type selective inhibitor, was demonstrated to have protective effects on rat MI/RI and its effects on histone acetylation level, HDAC1 and miR-210 expression in myocardial infarction area tissues after rat myocardial ischemia reperfusion; 3) the specific molecular mechanism of MS-275 for improving MI/RI of rats is revealed from the perspective of miRNA epigenetic regulation, and important theoretical and experimental basis is provided for treating MI/RI by HDACI.
Detailed Description
The present invention will be further described below, but the present invention is not limited to these.
Examples
The research method of the effect of MS-275 on acute myocardial ischemia-reperfusion injury comprises the following steps:
the method comprises the following steps: establishing an acute MI/RI model of the rat by performing left anterior descending coronary artery ligation on SD male rats: SD male rats 72 were randomly divided into 4 groups of 18 per group: wherein the first group is a Sham group (Sham group) with only threading and no ligation; the second group was ischemic 30-minute group (I30 min group); the third group was a 30-minute ischemia reperfusion 60-minute group (I/R60min group); the fourth group was an ischemia 30-minute reperfusion 2-hour group (I/R120 min group); after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the expression change of HDAC1 and miR-210 are detected through technologies such as immunohistochemistry, a histone acetylation detection kit, real-time PCR and the like.
Step two: the effect of MS-275 in the acute phase of MI/RI in rats was observed: SD male rats 90 were randomly divided into 3 groups of 30 per group: the first group is a Sham operation group (Sham group), which is not ligated by threading, and is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation, respectively; the second group is myocardial ischemia/reperfusion group (I/R group), which is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation respectively; the third group is myocardial ischemia/reperfusion + HDACI pretreatment group (I/R + MS-275 group), and MS-275(10mg/kg) was intraperitoneally injected 24 hours and 1 hour before the operation; ischemia/reperfusion time is 30min/120min, and hemodynamics and arrhythmia of rats in each group are monitored in the experimental process; after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the HDAC1 and the miR-210 expression change are detected;
step three: the molecular mechanism of MS-275 on the protection of rat MI/RI is explored: screening and identifying a downstream target gene FOXO3A of miR-210 by using methods such as bioinformatics, a dual-luciferase reporter gene system, interference over-expression and the like; MS-275 treats the H9c2 cell strain, and detects the level of miR-210 promoter zone protein H4ac, the expression of miR-210 and FOXO3A and the apoptosis condition before and after treatment; analyzing the correlation of miR-210 and FOXO3A expression in rat ischemia reperfusion myocardial infarction area tissues; the target gene resilience experiment proves that miR-210/FOXO3A mediates the myocardial protection effect of MS-275.
As a result: the LAD ligation and the release are carried out to successfully establish a rat MI/RI model; compared with the I30min group, the I/R120 min group can obviously reduce the level of the total histone H4ac in the tissues of myocardial infarction areas of rats (the vs I30min group of the I/R120 min group is 0.9745 +/-0.1247 vs 1.8090 +/-0.1796, P is less than 0.01), promote the protein expression of HDAC1 (P is 0.001), and inhibit the expression of miR-210 (the vs I30min group of the I/R120 min group is 4.5480 +/-0.7486 vs 12.4100 +/-1.9640, and P is less than 0.01).
MS-275 pre-ischemic pretreatment can obviously reduce the incidence rate of arrhythmia such as tachycardia, ventricular premature beat, ventricular fibrillation and the like caused by myocardial I/R of rats (P <0.01), obviously improve the function damage of ventricles and reduce the myocardial infarction area (I/R + MS-275 vs I/R group is 30.76 +/-2.0780 vs 46.80 +/-3.0590, and P < 0.01); compared with the I/R group, the level of H4ac in the myocardial tissue of rats in the I/R + MS-275 group is obviously increased (P <0.001), the level of HDAC1 is obviously reduced (P <0.001), the activity is obviously inhibited (I/R + MS-275 group vs I/R group is 3092 +/-189.7 vs 5163 +/-231.2, P is <0.001), and the expression level of miR-210 is obviously increased (I/R + MS-275 group vs I/R group is 9.9050 +/-0.8261 vs 4.5680 +/-0.6110, P is < 0.001).
Compared with the control group, the activity of HDAC1 in MS-275 group H9c2 cells is significantly reduced (MS-275 group vs control group is 1678 ± 156.9vs 3235 ± 205.5, P <0.001), miR-210 promoter region block protein H4ac level is significantly increased (MS-275 group vs control group is 2.3790 ± 0.2352vs1.0110 ± 0.0803, P <0.001), the expression of miR-210 is also significantly increased (MS-275 group vs control group is 2.9740 ± 0.4888vs 1.0170 ± 0.0982, P <0.01), and the apoptosis of H9c2 cells is significantly reduced (MS-275 group vs control group is 6.9250 ± 0.7471vs 13.9600 ± 0.9552, P < 0.001).
Bioinformatics prediction and dual-luciferase reporter gene detection suggest that FOXO3A may be a downstream target gene of miR-210; the interference of miR-210 in H9c2 cells can obviously increase the expression of FOXO3A (protein: Inhibitor vs INC is 3.2900 +/-0.5511 vs 1.0000 +/-0.0000, P is less than 0.01; mRNA: Inhibitor vs INC is 5.9050 +/-0.8525 vs 1.0230 +/-0.1064, P is less than 0.001), while the overexpression of miR-210 can obviously inhibit the expression of FOXO3A (protein: mimic vs MNC is 0.2667 +/-0.0596 vs 1.0000 +/-0.0000, P is less than 0.001; mRNA: mimic vs MNC is 0.2720 +/-0.0748 vs 0.9788 +/-0.0850, P is less than 0.001); compared with the I/R group, the expression of FOXO3A in myocardial tissues of rats with I/R + MS-275 is remarkably reduced (protein: I/R + MS-275 group vs I/R group is 0.1240 + -0.0239 vs 0.3340 + -0.0411, P is less than 0.01; mRNA: I/R + MS-275 group vs I/R group is 16.3300 + -2.4730 vs 33.1400 + -5.6750, P is less than 0.05), and the mRNA expression of FOXO3A is remarkably and negatively correlated with the expression of miR-210 (R is-0.6727, P is 0.0390); after interfering with miR-210 expression in MS-275 treated H9c2 cells, the effect of MS-275 in inhibiting apoptosis largely disappeared (MS-275+ inhibitor group vs MS-275+ INC group 13.5800 ± 1.0200vs 6.5950 ± 0.8586, P < 0.01); the over-expression of miR-210 in H9c2 cells can obviously inhibit apoptosis (Mimic + Plasmid control vs MNC + Plasmid control is 4.8730 + -0.4516 vs 12.5200 + -0.8256, P is less than 0.01), and after the expression of the target gene FOXO3A is restored, the apoptosis inhibition effect of miR-210 is reversed (Mimic + FOXO3A Plasmid vs Mimic + Plasmid control is 10.7500 + -0.8543 vs 4.8730 + -0.4516, P is less than 0.05).
And (4) conclusion: MS-275 pre-ischemic pretreatment can obviously reduce myocardial infarction area and arrhythmia incidence after I/R of rats, and obviously improve ventricular function, and has myocardial protection effect; the possible molecular mechanism is that MS-275 promotes miR-210 promoter histone H4ac, induces the expression of the latter to be increased, and further inhibits the apoptosis of the myocardial cells by regulating miR-210/FOXO3A axis.
It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention.
Claims (4)
- A research method for the effect of MS-275 on acute myocardial ischemia-reperfusion injury is characterized by comprising the following steps:the method comprises the following steps: establishing an acute MI/RI model of the rat by performing anterior descending ligation on the left coronary artery of the SD male rat;step two: observing the effect of MS-275 in the MI/RI acute phase of rats;step three: the molecular mechanism of MS-275 on the protection of rat MI/RI was explored.
- 2. The method of claim 1, wherein the MS-275 is administered to a subject suffering from acute myocardial ischemia reperfusion injury, wherein the subject is selected from the group consisting of: the first step comprises the following steps: SD male rats 72 were randomly divided into 4 groups of 18 per group: wherein the first group is a Sham group (Sham group) with only threading and no ligation; the second group was ischemic 30-minute group (I30 min group); the third group was a 30-minute ischemia reperfusion 60-minute group (I/R60min group); the fourth group was an ischemia 30-minute reperfusion 2-hour group (I/R120 min group); after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the expression change of HDAC1 and miR-210 are detected through technologies such as immunohistochemistry, a histone acetylation detection kit, real-time PCR and the like.
- 3. The method of claim 1, wherein the MS-275 is administered to a subject suffering from acute myocardial ischemia reperfusion injury, wherein the subject is selected from the group consisting of: the second step comprises the following steps: SD male rats 90 were randomly divided into 3 groups of 30 per group: the first group is a Sham operation group (Sham group), which is not ligated by threading, and is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation, respectively; the second group is myocardial ischemia/reperfusion group (I/R group), which is injected with a solvent DMSO into the abdominal cavity 24 hours and 1 hour before the operation respectively; the third group is myocardial ischemia/reperfusion + HDACI pretreatment group (I/R + MS-275 group), and MS-275(10mg/kg) was intraperitoneally injected 24 hours and 1 hour before the operation; ischemia/reperfusion time is 30min/120min, and hemodynamics and arrhythmia of rats in each group are monitored in the experimental process; after the experiment is finished, the rat is sacrificed, the heart is separated, a tissue specimen in the myocardial infarction area is reserved, the myocardial infarction area and the change of the cell tissue morphology in the myocardial infarction area are observed through section staining, and the histone acetylation level, the HDAC1 and the expression change of miR-210 are detected.
- 4. The method of claim 1, wherein the MS-275 is administered to a subject suffering from acute myocardial ischemia reperfusion injury, wherein the subject is selected from the group consisting of: the third step comprises: screening and identifying a downstream target gene FOXO3A of miR-210 by using methods such as bioinformatics, a dual-luciferase reporter gene system, interference over-expression and the like; MS-275 treats the H9c2 cell strain, and detects the level of miR-210 promoter zone protein H4ac, the expression of miR-210 and FOXO3A and the apoptosis condition before and after treatment; analyzing the correlation of miR-210 and FOXO3A expression in rat ischemia reperfusion myocardial infarction area tissues; the target gene resilience experiment proves that miR-210/FOXO3A mediates the myocardial protection effect of MS-275.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010377075.7A CN111575363A (en) | 2020-05-07 | 2020-05-07 | Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010377075.7A CN111575363A (en) | 2020-05-07 | 2020-05-07 | Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111575363A true CN111575363A (en) | 2020-08-25 |
Family
ID=72118786
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010377075.7A Pending CN111575363A (en) | 2020-05-07 | 2020-05-07 | Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111575363A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117752309B (en) * | 2024-02-22 | 2024-04-30 | 天津医科大学第二医院 | Method for evaluating protective effect of sevoflurane on myocardial ischemia reperfusion injury |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060205671A1 (en) * | 2003-07-02 | 2006-09-14 | Jakob Vinten-Johansen | Compositions and methods for use of a protease inhibitor and adenosine for preventing organ ischemia and reperfusion injury |
| US20090105168A1 (en) * | 2004-11-30 | 2009-04-23 | Gruber Peter J | Use Of HDAC And/Or DNMT Inhibitors For Treatment Of Ischemic Injury |
| CN102423308A (en) * | 2011-09-30 | 2012-04-25 | 山西医科大学 | Two bromophenol compounds and application of pharmaceutically-acceptable salts of two bromophenol compounds in preparation of protection drug |
| CN108283633A (en) * | 2017-01-06 | 2018-07-17 | 郑州大学 | The bromo- 2- of 5-（Alpha-hydroxy amyl）Application of the sodium benzoate in treating cardiovascular disease medicine |
-
2020
- 2020-05-07 CN CN202010377075.7A patent/CN111575363A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060205671A1 (en) * | 2003-07-02 | 2006-09-14 | Jakob Vinten-Johansen | Compositions and methods for use of a protease inhibitor and adenosine for preventing organ ischemia and reperfusion injury |
| US20090105168A1 (en) * | 2004-11-30 | 2009-04-23 | Gruber Peter J | Use Of HDAC And/Or DNMT Inhibitors For Treatment Of Ischemic Injury |
| CN102423308A (en) * | 2011-09-30 | 2012-04-25 | 山西医科大学 | Two bromophenol compounds and application of pharmaceutically-acceptable salts of two bromophenol compounds in preparation of protection drug |
| CN108283633A (en) * | 2017-01-06 | 2018-07-17 | 郑州大学 | The bromo- 2- of 5-（Alpha-hydroxy amyl）Application of the sodium benzoate in treating cardiovascular disease medicine |
Non-Patent Citations (3)
| Title |
|---|
| ZHIPING HU ET AL.: ""The Emerging Role of Epigenetics in Cerebral Ischemia"" * |
| 戴翠莲等: ""蛋白酶体抑制剂MG-132对大鼠急性心肌缺血再灌注损伤的保护作用研究"" * |
| 李维等: ""I型组蛋白去乙酰化酶在糖尿病大鼠心肌缺血再灌注损伤中的作用及其与AMPK/mTOR信号通路的关系"" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117752309B (en) * | 2024-02-22 | 2024-04-30 | 天津医科大学第二医院 | Method for evaluating protective effect of sevoflurane on myocardial ischemia reperfusion injury |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sovari | Cellular and molecular mechanisms of arrhythmia by oxidative stress | |
| Schiffrin | Vascular and cardiac benefits of angiotensin receptor blockers | |
| Wolke et al. | Redox control of cardiac remodeling in atrial fibrillation | |
| RU2316318C2 (en) | Pharmaceutical composition including renin inhibitor, calcium channel blocker and diuretic | |
| Liu et al. | Angiotensin-(1–7) prevents atrial fibrosis and atrial fibrillation in long-term atrial tachycardia dogs | |
| Hoogstra-Berends et al. | Heat shock protein–inducing compounds as therapeutics to restore Proteostasis in atrial fibrillation | |
| PL195634B1 (en) | Derivatives of hydroxylamine useful as compounds enhancing production of accompanying molecular protein and ethod of obtaining them | |
| Liu et al. | Enalapril, irbesartan, and angiotensin-(1–7) prevent atrial tachycardia-induced ionic remodeling | |
| WO2003059346A1 (en) | Beta-secretase inhibitors | |
| Naccarelli et al. | Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction | |
| CN111575363A (en) | Research method for MS-275 acting on acute myocardial ischemia-reperfusion injury | |
| Matus et al. | Upregulation of SERCA2a following short-term ACE inhibition (by enalaprilat) alters contractile performance and arrhythmogenicity of healthy myocardium in rat | |
| Dai | CPU86017: a novel Class III antiarrhythmic agent with multiple actions at ion channels | |
| Maltês et al. | New perspectives in the pharmacological treatment of hypertrophic cardiomyopathy | |
| Acsai et al. | Antiarrhythmic potential of drugs targeting the cardiac ryanodine receptor Ca2+ release channel: case study of dantrolene | |
| Holtz | The cardiac renin-angiotensin system: physiological relevance and pharmacological modulation | |
| Blaauw et al. | Inhibitors of the Na+/H+ exchanger cannot prevent atrial electrical remodeling in the goat | |
| Yang et al. | A1059 Telmisartan upregulates ACE2-Ang-(1–7)-Mas axis and affects retinal vessel endothelial cell apoptosis | |
| US20150190472A1 (en) | Use of the angiotensin-(1-9) peptide or derivatives thereof, use of vectors overexpressing the ace2 enzyme that produces angiotensin-(1-9) for preparing medicaments useful for preventing, reverting, inhibiting and/or reducing hypertension and/or inducing vasodilation | |
| An et al. | Role and Mechanism of MicroRNA-7a-5p in Paraventricular Nucleus on Sympathetic Overactivity in the Spontaneously Hypertensive Rats | |
| Yang et al. | A1046 MicroRNA-29b Ameliorates Hypertensive Renal Dysfunction via Suppression of the TGF-β-induced epithelial-mesenchymal transition and extracellular matrix synthesis | |
| Zhong et al. | A1156 Cardioprotective effects of Apelin-13 on aging-and angiotensin II-mediated adverse myocardial injury and dysfunction in hypertensive mice | |
| Mueller et al. | Flecainide: a new antiarrhythmic drug | |
| Miao et al. | Advances in angiotensin-(1-7) and atrial fibrillation. | |
| Zhao et al. | Cilostazol ameliorates atrial ionic remodeling in long-term rapid atrial pacing dogs. |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200825 |