CN117323320A - Application of long-chain fatty acid 12-HHT in sleep apnea and hypertension - Google Patents
Application of long-chain fatty acid 12-HHT in sleep apnea and hypertension Download PDFInfo
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- KUKJHGXXZWHSBG-GMPNNLDHSA-N 12-HHTrE Chemical compound CCCCCC(O)\C=C\C=C\C\C=C\CCCC(O)=O KUKJHGXXZWHSBG-GMPNNLDHSA-N 0.000 title claims abstract description 50
- 206010020772 Hypertension Diseases 0.000 title claims abstract description 33
- 201000002859 sleep apnea Diseases 0.000 title claims abstract description 28
- 150000004668 long chain fatty acids Chemical class 0.000 title claims abstract description 25
- 208000001797 obstructive sleep apnea Diseases 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 24
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 3
- 239000003596 drug target Substances 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 229920002253 Tannate Polymers 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229940049920 malate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 150000003384 small molecules Chemical class 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000008685 targeting Effects 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 abstract description 19
- 230000007954 hypoxia Effects 0.000 abstract description 16
- 210000002889 endothelial cell Anatomy 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 5
- 230000005012 migration Effects 0.000 abstract description 5
- 238000013508 migration Methods 0.000 abstract description 5
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 17
- 239000001301 oxygen Substances 0.000 description 17
- 241000700159 Rattus Species 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000001146 hypoxic effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 101001017969 Homo sapiens Leukotriene B4 receptor 2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021079 Hypopnoea Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100033375 Leukotriene B4 receptor 2 Human genes 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical group CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 210000004082 barrier epithelial cell Anatomy 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 230000004890 epithelial barrier function Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an application of long-chain fatty acid 12-HHT in sleep apnea and hypertension, and belongs to the field of biological medicines. In particular to a method for preparing a drug or reagent for diagnosing or treating sleep apnea and hypertension by taking 12-HHT as a diagnostic target or a drug target, wherein the molecular formula of the 12-HHT is C 17 H 28 O 3 The structural formula isWherein sleep apnea and hypertension are combined with obstructive sleep apnea and hypopnea syndrome and hypertension, and the medicine can be targeted medicine, and 12-HHT is used as a target point. The invention discovers that 12-HHT can inhibit excessive increase of endothelial cells caused by intermittent hypoxia through an intermittent hypoxia endothelial cell modelThe medicine plays a role in treatment by reproduction and migration, proves that the medicine is used as an effective intervention target spot for combining OSAHS with hypertension, and provides a brand new potential therapeutic medicine for patients of the type.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to application of long-chain fatty acid 12-HHT in sleep apnea and hypertension.
Background
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a systemic disease that occurs during nocturnal sleep when the upper airway is partially or completely blocked, causing recurrent episodes of apnea and hypopnea, ultimately leading to cardiovascular and cerebrovascular complications.
OSAHS is one of the most common causes of secondary hypertension, and the severity of OSAHS is often positively correlated with the degree of elevation of blood pressure levels. At present, for patients with sleep apnea complicated with hypertension, the simple medicament has poor antihypertensive effect, and the influence of non-invasive positive airway pressure on the blood pressure level of the patients is quite limited, even if one or more antihypertensive medicaments are added for treatment on the basis of the treatment, the occurrence and death of cardiovascular events can not be completely blocked. Therefore, aiming at the problem of poor treatment effect of sleep apnea and hypertension, it is highly demanded to diagnose and optimize the treatment means of the existing medicines as soon as possible.
Disclosure of Invention
In order to overcome the problem of poor antihypertensive effect in the prior art for treating OSAHS-associated hypertension, the invention aims to provide the application of long-chain fatty acid 12-HHT as a diagnosis target or a medicine target in preparing medicines or reagents for diagnosing or treating sleep apnea-associated hypertension, wherein the long-chain fatty acid 12-HHT is a metabolite of arachidonic acid through an Cyclooxygenase (COX) pathway, is a low-affinity ligand of BLT2, has CAS number of 100679-07-0 and molecular formula of C 17 H 28 O 3 Molecular weight is 280.40, and structural formula is
Preferably, the sleep apnea and hypertension refers to obstructive sleep apnea and hypopnea syndrome and hypertension.
The invention also provides a pharmaceutical composition which is a targeting drug and takes long-chain fatty acid 12-HHT as a target point.
The invention also provides the application of the long-chain fatty acid 12-HHT or the pharmaceutically acceptable salt thereof in preparing medicaments for treating sleep apnea and hypertension, wherein the molecular formula of the long-chain fatty acid 12-HHT is C 17 H 28 O 3 The structural formula is
Preferably, the sleep apnea and hypertension refers to obstructive sleep apnea and hypopnea syndrome and hypertension.
Preferably, the pharmaceutically acceptable salt of the long-chain fatty acid 12-HHT is selected from one or more of hydrochloride, hydrobromide, sulfate, acetate, lactate, tartrate, tannate, citrate, trifluoroacetate, malate, maleate, succinate, p-toluenesulfonic acid or benzenesulfonate.
The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of long chain fatty acid 12-HHT and/or a pharmaceutically acceptable salt thereof, wherein the long chain fatty acid 12-HHT has the formula C 17 H 28 O 3 The structural formula is
Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, and can be prepared into injection, emulsion, tablet, powder, granule, ointment, liposome or oral liquid.
The invention also provides a small molecule injection preparation which comprises a therapeutically effective amount of long chain fatty acid 12-HHT with a molecular formula of C 17 H 28 O 3 The structural formula isWherein the concentration of the long-chain fatty acid 12-HHT is 0.1-100. Mu. Mol/L, preferably 3. Mu. Mol/L.
The prior literature reports that 12-HHT has the functions of regulating allergic reaction, repairing epithelial barrier and the like, the invention proves that the 12-HHT has correlation with OSAHS combined hypertension through the serometabonomics detection of each group of human and rats, meanwhile, the intermittent hypoxia endothelial cell model experiment discovers that the 12-HHT can play a role in treating the cell model through excessive migration resistance and the like, and can be used as an effective intervention target point of the OSAHS combined hypertension for preparing the medicament for treating sleep apnea combined hypertension, thereby optimizing the treatment means of the prior medicament and providing a brand-new potential treatment medicament for patients. In addition, 12-HHT is an endogenous fatty acid and has better drug safety.
Drawings
FIG. 1 shows the relative abundance of 12-HHT in serum from each group of patients and healthy human and rat in the examples.
FIG. 2 is a graph showing the effect of 12-HHT on the proliferation phenotype of intermittent hypoxic endothelial cells in the examples; a: edU detection results of human primary umbilical vein endothelial cells (HUVECs) of each group; b: edU positive cell statistics for each group of HUVECs.
FIG. 3 is the effect of 12-HHT on intermittent hypoxic endothelial cell migration phenotype in the examples (scoring experiments); a: scratch test results for each group of HUVECs; b: statistical graphs of HUVEC healing rates for each group.
FIG. 4 is a graph showing the effect of 12-HHT on the migration phenotype of intermittent hypoxic endothelial cells in the examples (transwell experiments); a: transwell staining results for each group of HUVECs; b: statistical graphs of the number of migrating cells of each group of HUVECs.
Detailed Description
The present invention will be described in further detail by way of examples, but the present invention is not limited to these examples.
Example 1
Primary hypertension patients (HTN group), OSAHS patients (OSAHS group) and OSAHS combined hypertension patients (osahs+htn group) without taking antihypertensive drugs, which were diagnosed in cardiology department and respiratory department of secondary university affiliated midmountain hospitals, were selected between 1 month 2021 and 10 months 2022. In addition, the group matched with the clinical characteristics of the clinic visit in the physical examination center is selected as a healthy control group (CON group), the control group needs to exclude hypertension and OSAHS, and the non-targeted metabolome detection of serum is completed for all subjects. Meanwhile, for standard clinical samples (in order to distinguish from clinical samples, rats are grouped in a 'uppercase + lowercase' format in the first part of the study), a rat model queue of intermittent hypoxia (Osahs group), intermittent hypoxia combined hypertension (Osahs + Htn group) and a control group (Con group) is established. The non-targeted metabonomics of the rat serum was also tested and compared with the results of clinical patients and the specific procedures and results were as follows:
(1) Relative abundance experiments of serum 12-HHT for each group of patients and healthy people: patients who were enrolled in the department of cardiology and respiratory medicine of the department of the middle mountain hospital of the double denier university from 1 month 2021 to 10 months underwent a total of 125 cases including 40 cases in HTN group, 30 cases in OSAHS group, 55 cases in osahs+htn group, and 38 cases in CON group in addition to the physical examination center. The serometabonomics of the above population was examined and found that 12-HHT showed statistical differences in the pairwise comparison of OSAHS group, OSAHS+HTN group and CON group.
(2) Relative abundance experiments of serum 12-HHT from rats of each group: male wistar rats were divided into 3 groups as follows: osahs experimental group (5, 8 weeks of age), osahs+htn experimental group (4, 8 weeks of age), con group (5, 8 weeks of age). The experimental group was given continuous intermittent anoxic stimulation during the day (9 am-7pm, total 10 h) where the sleep phase of the rats was dominant, and the oxygen partial pressure parameter was set to cycle in the range of about 6.5% -21%, and cycle 1 period was set to 220s. Starting with the hypoxia period, oxygen is then fed into the animal experiment box for 25s, the oxygen concentration is slowly increased to 21% and kept at the oxygen concentration of 21% for 90s, then nitrogen is fed into the animal experiment box for 45 s, the oxygen concentration is slowly decreased to 6.5% and kept at the oxygen concentration of 6.5% for 60s, and the cycle is repeated. The constant oxygen or low oxygen plateau, the programmed controller automatically supplements the oxygen consumed by the rat vital activity to ensure that the oxygen concentration is stably maintained at about 21% or 6.5%. Modeling, the intermittent hypoxia stimulation time is 4h on day 1, the intermittent hypoxia stimulation time is increased to 7h on day 2, and the intermittent hypoxia stimulation time is 10h on day 3 until modeling is finished. And if the carbon dioxide content in the high-low oxygen box is greater than 1% in the experimental process, sodium lime is put into the high-low oxygen box for absorption. Wherein the Osahs experimental group is stimulated by intermittent hypoxia for 2 weeks, and the Osahs+Htn group is stimulated by intermittent hypoxia for 8 weeks. The Con group maintained constant oxygen partial pressure (21%) during the experiment, the remaining conditions unchanged for 8 weeks; the rats in each of the above groups were then subjected to serum metabonomics and 12-HHT was found to exhibit statistical differences in pairwise comparisons between groups.
The metabolome results for human and rat are shown in figure 1, which shows that long chain fatty acid 12-HHT in human and rat serum has significant and consistent changes in both the OSAHS group and the OSAHS-combined hypertensive group. In addition, from the metabonomics results of the patient subjects, 12-HHT was found to have no significant difference in comparison of the CON group and the HTN group. From this, it was demonstrated that 12-HHT is significantly associated with OSAHS-associated hypertension and can be used as a potential biomarker for OSAHS-associated hypertension.
Example 2
The construction of an intermittent hypoxia endothelial cell model in this example verifies the effect of 12-HHT on the proliferation and migration phenotype of intermittent hypoxia endothelial cells, and the specific operation and results are as follows:
human primary umbilical vein endothelial cells (HUVECs) were divided into 4 groups: the cell proliferation level was analyzed by the EdU method in a normoxic group (Nx group), a normoxic +12-HHT group (Nx +12-HHT group), an intermittent anoxic group (IH group) and an intermittent anoxic +12-HHT group (IH +12-HHT group), and the change in cell migration was evaluated by a scratch test and a transwell test. Wherein the intermittent anoxic mode is as follows: and (3) introducing binary gas into the cell culture box for 2min with a cycle period of 50min, slowly reducing the oxygen concentration to about 1%, maintaining the oxygen concentration at 1% -2% for 15min, then introducing ternary mixed gas into the cell culture box for 3min, slowly reducing the oxygen concentration to about 21%, maintaining the oxygen concentration at 20% -21% for 30min, and circulating for 24h to construct the cell intermittent hypoxia model. The normoxic control group had a gas atmosphere of 21% O during the experiment 2 ，5％CO 2 Residual% N 2 The remaining conditions were the same as those of the intermittent anoxic group.
As shown in the results of figures 2 to 4, the addition of 3 mu mol/L12-HHT in an intermittent hypoxia endothelial cell model proves that the 12-HHT can inhibit the excessive proliferation and excessive migration of HUVEC caused by intermittent hypoxia, and the 12-HHT can be used as an effective intervention target for OSAHS combined hypertension, so that a brand new potential therapeutic drug is provided for patients of the type, and the method has important clinical application value.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (9)
1. Application of long-chain fatty acid 12-HHT as diagnostic target or drug target in preparation of drug or reagent for diagnosing or treating sleep apnea and hypertension, wherein molecular formula of long-chain fatty acid 12-HHT is C 17 H 28 O 3 The structural formula is
2. The use according to claim 1, wherein the sleep apnea and hypertension is obstructive sleep apnea and hypopnea syndrome and hypertension.
3. The use according to claim 1, wherein the medicament is a targeted medicament targeting long chain fatty acid 12-HHT.
4. Use of long-chain fatty acid 12-HHT or pharmaceutically acceptable salts thereof for the manufacture of a medicament for the treatment of sleep apnea complicated with hypertension, wherein the long-chain fatty acid 12-HHT has the formula C 17 H 28 O 3 The structural formula is
5. The use according to claim 4, wherein the sleep apnea and hypertension is obstructive sleep apnea and hypopnea syndrome and hypertension.
6. The use according to claim 4, wherein the pharmaceutically acceptable salt of long-chain fatty acid 12-HHT is selected from one or more of hydrochloride, hydrobromide, sulfate, acetate, lactate, tartrate, tannate, citrate, trifluoroacetate, malate, maleate, succinate, p-toluenesulfonic acid or benzenesulfonate.
7. A pharmaceutical composition comprising a therapeutically effective amount of long chain fatty acid 12-HHT and/or a pharmaceutically acceptable salt thereof, wherein the long chain fatty acid 12-HHT has the formula C 17 H 28 O 3 The structural formula is
8. The pharmaceutical composition of claim 7, further comprising a pharmaceutically acceptable carrier or excipient, which is formulated as an injection, emulsion, tablet, powder, granule, ointment, liposome, or oral liquid.
9. A small molecule injectable preparation comprising a therapeutically effective amount of long chain fatty acid 12-HHT of formula C 17 H 28 O 3 The structural formula isWherein the concentration of the long-chain fatty acid 12-HHT is 0.1-100 mu mol/L.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311550044.7A CN117323320A (en) | 2023-11-20 | 2023-11-20 | Application of long-chain fatty acid 12-HHT in sleep apnea and hypertension |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311550044.7A CN117323320A (en) | 2023-11-20 | 2023-11-20 | Application of long-chain fatty acid 12-HHT in sleep apnea and hypertension |
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| CN117323320A true CN117323320A (en) | 2024-01-02 |
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| CN202311550044.7A Pending CN117323320A (en) | 2023-11-20 | 2023-11-20 | Application of long-chain fatty acid 12-HHT in sleep apnea and hypertension |
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| Country | Link |
|---|---|
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