CN117599070A - Application of tigecycline in preparation of medicine for treating atherosclerosis - Google Patents
Application of tigecycline in preparation of medicine for treating atherosclerosis Download PDFInfo
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- tigecycline
- density lipoprotein
- low density
- macrophages
- lipoprotein cholesterol
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- 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
- A61K31/65—Tetracyclines
-
- 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
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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Abstract
The invention belongs to the technical field of new application of medicines, and particularly relates to application of tigecycline in preparation of medicines for treating atherosclerosis. In particular, the invention provides application of tigecycline in preparing medicines for preventing and eliminating atherosclerosis plaques. In addition, the invention also provides application of tigecycline in preparing medicaments for regulating and controlling the phagocytic oxidation of low-density lipoprotein cholesterol function of macrophages.
Description
Technical Field
The invention belongs to the technical field of new application of medicines, and particularly relates to application of tigecycline in preparation of medicines for treating atherosclerosis.
Background
Atherosclerosis (AS) is a common cause of heart attacks and strokes, and aortic atherosclerotic cardiovascular disease (ASCVD) is a disease with high disability and mortality, accounting for about 61% of the mortality of cardiovascular disease (CVD). At present, according to different severity of AS, the adopted treatment schemes are different, and AS patients with severe vascular stenosis and blockage in acute and severe diseases need surgical bypass, stent treatment is assisted with antiplatelet, anti-vasospasm and lipid-lowering treatment, and remission stage and light and medium AS drug treatment are mainly oral drug treatment for a long time. Statin is used AS a first-line drug for standardized treatment of atherosclerosis, and according to clinical reports, the statin has the main effect of reducing blood lipid, but has the effect of slightly reducing atheromatous plaque when being continuously used for more than 6 months on AS plaque resistance. However, the medicine has the irreversible toxic and side effects of low bioavailability, cardiovascular residual risk, liver function injury, blood sugar rise and the like of patients caused by long-term and large-dose (extremely high-risk ASCVD patients) administration, reduces patient compliance and limits clinical application of the medicine; and disabling the statin increases the probability of cardiovascular events. Thus, it is urgent to develop a high-efficiency and low-toxicity drug for preventing or treating AS.
AS is known to belong to a metabolic disease closely related to vascular cell inflammation, and thus, technical ideas for treatment with antibacterial drugs have been proposed in the prior art. For example, literature Effect of antibiotics as cholesterol-lower agents (publication date 20051231) discloses that some antibiotics were proposed as hypercholesterolemia drugs 30 years ago, but the mechanism is not well defined and this phenomenon was relatively unexplored. The document further suggests that common antibiotics (including metronidazole, ciprofloxacin, etc.) can reduce the blood lipid risk factors of cardiovascular diseases, and the use of antibiotics can lead to a significant physiological reduction of serum lipid risk factors of cardiovascular diseases. It follows that the main mechanism of antibiotic treatment AS reported in this document is lipid lowering. The patent with the application number of CN201910620034.3 and the name of pefloxacin for treating and preventing hyperlipidemia or atherosclerosis is disclosed, and the pefloxacin can obviously reduce the levels of cholesterol, triglyceride and low-density lipoprotein in serum of experimental high-fat rats, thereby improving the lipid metabolism disorder state of the rats and preventing hyperlipidemia or atherosclerosis. It is evident that the use of antibiotics/antiseptics to treat AS in the current state of the art is mainly directed to lowering serum cholesterol, triglycerides or low density lipoproteins levels, similar to statin treatment ideas. Reports have not been seen that reveal relevant mechanisms from other uses and for clinical practice.
In view of the foregoing, there is a need for new methods and strategies that complement the deficiencies of the prior art.
Disclosure of Invention
In view of the above, the invention aims to provide a new application of tigecycline, and the specific technical scheme is as follows.
Use of tigecycline for the manufacture of a medicament for preventing and eliminating atherosclerotic plaques, said tigecycline being used for preventing formation of atherosclerotic plaques on the intima of an artery (slowing the rate and progress of plaque formation) and/or eliminating atherosclerotic plaques already formed on the intima of an artery.
Further, the tigecycline is used to inhibit phagocytosis of oxidized low density lipoprotein cholesterol by macrophages to form foam cells.
Further, the tigecycline is used to inhibit macrophage phagocytic oxidation of low density lipoprotein cholesterol function at a half maximal effector concentration (EC 50) of less than 2 μg/ml.
According to the revised 'tigecycline specification for injection' of 11 months in 2021, the drug sensitive dose of enterobacteria and anaerobic bacteria is 2-4 mug/mL, the EC50 value of the tigecycline in vitro anti-macrophage lipid drop phagocytic function is 1.2 mug/mL, the concentration is only 30% -60% of the drug sensitive concentration, and the drug can generate an AS plaque resisting effect below the antibacterial concentration, so that the effect on flora is small.
Further, the medicament is prepared in dosage unit form, formulated as a single use, individual dosage form containing 50-80mg of tigecycline, and formulated as one dosage unit in 30 individual dosage forms.
In the present invention, the concentration levels desirably administered to the compound are generally effective for achieving an effective use for eliminating atherosclerotic plaque formation and/or inhibiting atherosclerotic plaque formation in an arterial intima, but not achieving effective concentration levels at which the present compound is conventionally used as an antibiotic.
Preferably, the unit dose is a daily dose containing the above-mentioned active ingredient or a divided dose as a treatment cycle.
Further, the pharmaceutical dosage forms include injections, oral solutions and/or tablets; pharmaceutically acceptable carriers and/or adjuvants may also be included in the medicament.
Alternatively, the injection may be administered by subcutaneous, intradermal, intralesional, intraperitoneal, intravenous, or the like. Oral agents include aqueous solutions and tablets, which are administered orally (orally or sublingually).
Formulations suitable for injection or oral administration are presented in discrete dosage units so that they may be administered as a predetermined amount of the active ingredient. Such as solutions or suspensions in aqueous or non-aqueous liquids; capsules or tablets; powder or granule, etc.
The term "pharmaceutically acceptable" as used herein refers to compounds, materials, compositions, and/or dosage forms which are, within the reasonable scope of medical judgment, suitable for use in contact with the tissues of patients without excessive toxicity, irritation, allergic response, or other problem and complication commensurate with a reasonable benefit/risk ratio, and are effective for use in the intended use.
Pharmaceutically acceptable carriers and/or adjuvants described herein include, but are not limited to, solvents, diluents, excipients, and the like, and are added at appropriate steps in the manufacturing process.
Application of tigecycline in preparing medicine for regulating and controlling macrophage phagocytic oxidation of low density lipoprotein cholesterol.
Further, the tigecycline is used to inhibit expression of pro-inflammatory factors in macrophages phagocytosed oxidized low density lipoprotein cholesterol; alternatively, the expression of inflammatory factors within macrophages engulfed by oxidized low density lipoprotein cholesterol is promoted.
Further, the tigecycline is used to down-regulate the levels of phosphorylated proteins in the NF- κb signaling pathway and PI3K/AKT/mTOR signaling pathway.
Further, the tigecycline is used to down-regulate expression of an autophagic protein in macrophages phagocytosed by oxidized low density lipoprotein cholesterol; alternatively, up-regulation of autophagic protein expression in macrophages phagocytosed oxidized low density lipoprotein cholesterol.
Further, the tigecycline is used to inhibit cell migration of vascular smooth muscle.
Beneficial technical effects
1) The invention provides a new application of tigecycline: use for preventing and eliminating atherosclerotic plaques. Tigecycline is a known antibiotic, and although there are literature reports that antibiotics/antibacterials have a certain effect in treating atherosclerosis, the literature reports disclosed are all used for treating or relieving atherosclerosis from the standpoint of lipid lowering (such as cholesterol, triglyceride, low density lipoprotein, other fatty acid, etc.), and the problem is not solved from the standpoint of atherosclerotic plaques.
2) The EC50 value of the tigecycline used for preventing and eliminating the atherosclerosis plaque is 1.2 mug/mL, and the drug is used as the antibiotic antibacterial drug sensitive dose of 2-4 mug/mL. Document Effect of antibiotics as cholesterol-lower agents (publication date 20051231) discloses that antibiotics are able to alter colonic microorganisms and thereby affect cholesterol metabolism. However, the invention proves that the tigecycline can generate an AS plaque resisting effect when the concentration is lower than the antibacterial concentration, has small influence on intestinal flora, and shows that the application of the tigecycline in preventing and eliminating atherosclerosis plaque is a brand-new application.
3) The animal experiments further prove that the atheromatous plaque accounts for about 7% of the area of the lumen after 1 month of the tigecycline, and the atheromatous plaque is remarkably reduced compared with the atheromatous plaque of the control group without the tigecycline, which accounts for about 40% of the total area of the lumen. The first-line standard medicine for treating AS clinically at present needs to be continuously used for more than 6 months to slightly reduce atheromatous plaque.
4) The invention also provides an application of tigecycline in regulating and controlling the function of phagocytic oxidation of low-density lipoprotein cholesterol by macrophages.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. Like elements or portions are generally identified by like reference numerals throughout the several figures. In the drawings, elements or portions thereof are not necessarily drawn to scale. It will be apparent to those of ordinary skill in the art that the drawings in the following description are of some embodiments of the invention and that other drawings may be derived from these drawings without inventive faculty.
FIG. 1 is a graph of experimental results of normal macrophages treated with varying concentrations of tigecycline;
FIG. 2 is a graph of experimental results of oxLDL-induced macrophages treated with varying concentrations of tigecycline (red arrows and boxes indicate the number of punctate lipid droplets per unit cell);
FIG. 3 is an experimental graph of tigecycline regulating oxLDL-induced macrophage inflammatory signaling pathway at the mRNA level (A: IL-1β, B: IL-18; C: IL-6; D: TNF- α; E: COX-2, F: IL-10);
FIG. 4 is a graph showing experimental regulation of oxLDL-induced macrophage inflammatory factor secretion by tigecycline at the protein level (A: IL-1β, B: IL-6, C: IL-10);
FIG. 5 is an experimental graph of tigecycline inhibiting oxLDL-induced inflammatory protein expression in macrophages (A: protein band diagram, B: p-NF- κB, C: p-IκBα, D: IL-1β, E: IL-18);
FIG. 6 is an experimental graph of tigecycline inhibiting oxLDL induced expression of mTOR pathway protein in macrophages (A: protein band diagram, B: p-PI3K/PI3K, C: p-AKT/AKT, D: p-mTOR/mTOR);
FIG. 7 shows the results of an experiment for tigecycline up-regulating oxLDL induced autophagy protein expression in macrophages (A: protein band pattern, B: P62, C: bcl-1, D: LC3-II/LC 3-I);
FIG. 8 is a graph of an experimental view of tigecycline inhibiting vascular smooth muscle cell migration;
FIG. 9 is a graph showing experimental results of tigecycline slowing the progression of atherosclerosis in animals.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Herein, "and/or" includes any and all combinations of one or more of the associated listed items.
Herein, "plurality" means two or more, i.e., it includes two, three, four, five, etc.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.
As used in this specification, the term "about" is typically expressed as +/-5% of the value, more typically +/-4% of the value, more typically +/-3% of the value, more typically +/-2% of the value, even more typically +/-1% of the value, and even more typically +/-0.5% of the value.
In this specification, certain embodiments may be disclosed in a format that is within a certain range. It should be appreciated that such a description of "within a certain range" is merely for convenience and brevity and should not be construed as a inflexible limitation on the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all possible sub-ranges and individual numerical values within that range. For example, a rangeThe description of (c) should be taken as having specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within such ranges, e.g., 1,2,3,4,5, and 6. The above rule applies regardless of the breadth of the range.
Noun interpretation
The invention is described as "Regulation and controlMacrophage phagocytosis oxidized low density lipoprotein cholesterol function "includes up-regulation and down-regulation.
The "macrophages phagocytosed oxidized low density lipoprotein cholesterol" described in the present invention include macrophages induced by oxidized low density lipoprotein cholesterol in experiments and macrophages phagocytosed oxidized low density lipoprotein cholesterol in real in vivo environments.
Macrophages phagocytose oxidized low density lipoprotein cholesterol (oxLDL) to form foam cells that constitute early plaques of AS, a key element in the progression of AS. The invention uses tigecycline (0-10 mu M) with different concentrations to treat foam cells formed by oxidized low density lipoprotein cholesterol (oxLDL) induced macrophages, and examines the ability of the tigecycline to regulate the phagocytic lipid of the macrophages and form the foam cells.
Example 1
Treatment of normal macrophages with tigecycline
The experimental method comprises the following steps:
1. the concentrations of experimental tigecycline treated normal macrophages were respectively: 0. Mu.M, 0.3125. Mu.M, 0.625. Mu.M, 2.5. Mu.M, 5. Mu.M, 10. Mu.M.
2. MedicineToxicity test of the uninduced normal macrophages was performed in 96-well cell culture plates, first by counting cells in the logarithmic growth phase according to 1X 10 4 Cell mass/well, while cells were treated with tigecycline at different concentration gradients. The culture medium for drug concentration is diluted from high to low according to an equal proportion, the highest concentration is 10 mu M, the lowest concentration is 0.3125 mu M, the solvent group cell culture medium is added with solvent DMSO (Control group) with the same volume as the drug, and the DMSO content in each Control group hole is 1/1000. After 48 hours of drug treatment of all cells, CCK8 cell activity assay and cell count were performed, respectively, and the effect of drug on cell activity at different concentrations was counted (fig. 1). As can be seen from FIG. 1, the tigecycline concentration between 0.3125 and 10 μm has no significant effect on the uninduced normal macrophage activity compared to the solvent group, indicating that tigecycline has low cytotoxicity to normal cells and a large safety dose range.
Example 2
oxLDL-induced macrophages with tigecycline
The experimental method comprises the following steps:
1. the tigecycline concentrations are respectively: 0. Mu.M, 0.625. Mu.M, 2.5. Mu.M, 5. Mu.M, 10. Mu.M.
2. oxLDL induced macrophage-forming foam cells were treated with tigecycline at no concentration (0. Mu.M, 0.625. Mu.M, 2.5. Mu.M, 5. Mu.M, 10. Mu.M). The oxLDL-induced macrophages were found to be filled with red rice-like size material (indicated by red arrows) by staining with oil red "O" (ORO), suggesting that oxLDL-induced macrophages have increased lipid droplet phagocytosis and conversion to foam cells, as compared to the control group (macrophages not induced with oxLDL). After treatment with different concentrations of tigecycline, the phagocytic amount of the macrophage lipid drop decreased (red rice-like substance decreased), the dose-dependent decrease was shown with the drug concentration, and the EC50 value was 1.2 μm, suggesting that tigecycline could significantly inhibit the lipid phagocytic function of macrophages, and thus the foaming change (fig. 2).
Further examination of mRNA levels of various inflammatory factors in tigecycline-treated oxLDL-induced macrophages was found, and down-regulation of mRNA levels of pro-inflammatory factors IL-1β, IL-18, IL-6, TNF- α, COX2 was found with increasing tigecycline concentration, while inhibition of mRNA levels of inflammatory factor IL-10 was up-regulated with increasing tigecycline concentration (FIG. 3).
The protein levels of the above (partially typical) inflammatory factors were simultaneously detected by ELISA and WB, and the results were identical to those of FIG. 3 (FIG. 4). It was further found that, in addition to leukotriene-like inflammatory substances such as IL-1. Beta., IL-18, both the phosphorylated p65 (p-p 65) and phosphorylated IκBα (p-IκBα) of inflammatory proteins in the NF- κB signaling pathway decrease with increasing drug concentration (FIG. 5). The level of phosphorylation of core protein PI3K, AKT, mTOR in PI3K/AKT/mTOR signaling pathway (p-PI 3K, p-AKT, p-mTOR) decreased with increasing drug concentration, suggesting that tigecycline inhibits oxLDL-induced macrophage inflammation by modulating both NF- κb signaling pathway and PI3K/AKT/mTOR signaling pathway (fig. 6).
Further, the condition of autophagy protein expression in oxLDL-induced macrophages and vascular smooth muscle cells were examined. This experiment found that in oxLDL-induced macrophages, the expression levels of the autophagy-promoting proteins Bcl1 and LC3-ii/LC3-i were down-regulated, while the autophagy-inhibiting protein P62 was up-regulated. In contrast, the levels of expression of the drug-induced autophagy marker proteins Bcl1 and LC3-II/LC3-I were up-regulated in each dose group compared to the oxLDL-alone treated group (model group, 0. Mu.M), the autophagy-inhibiting protein P62 was down-regulated, and the concentration of the oxLDL-induced protein expression and drug concentration in macrophages exhibited a significant dose-concentration effect at 0.625. Mu.M, 2.5. Mu.M, and 10. Mu.M (FIG. 7).
Further, treatment of vascular smooth muscle cells with tigecycline showed a significant decrease in the migration capacity of the cells (fig. 8).
Together, the results show that tigecycline can inhibit proliferation of foam cells by promoting autophagy of cells and inhibit migration of vascular smooth muscle cells, so that occurrence and development of AS are inhibited at a cellular level.
Example 3
Model mice for model atherosclerosis were constructed and after 45 days of High Fat Diet (HFD) given to C57/BL6 mice, HFD fed mice were randomized into control (solvent) and dosing (tigecycline) groups. Mice continued to be given HFD while each mouse was given an intraperitoneal injection of 10mg/kg tigecycline per day, and the control group was given an equal volume of solvent for 30 consecutive days. Mouse serum and aortic samples were collected and assayed for changes in the atherosclerosis-related index.
The HE staining and the oil red O staining result show that the black square frame and the corresponding high-power mirror observation result show that the rat aortic intima of the control group in the white dotted line graph protrudes to the vascular cavity in a large area, obvious fat cells are accumulated, smooth muscle cells are arranged in disorder, the rat arterial formation of the control group is prompted to form severe atherosclerosis plaques, only the rat aortic intima of the administration group sees weak atherosclerosis plaques, the vascular smooth muscle arrangement is regular, and tigecycline is prompted to effectively inhibit the development of atherosclerosis of the rat (figure 9).
The dose administered to mice was converted to the dose for adults: according to the drug dose conversion standard between human and different animals provided by pharmacological experiment methodology, the ratio of human to mouse is 1:9.1-12.4 according to the equivalent dose ratio of body surface area conversion. The daily dosage of the mice with the dosage of 10mg/kg is corresponding to 0.81-1.1mg/kg of human body, thus the daily dosage of the mice with the dosage of 70kg is only 56.5-76.9mg.
Tigecycline is known to be used as an antibiotic for the treatment of infections in clinical patients at a daily dose of 100mg tigecycline. The result of the invention shows that the effective anti-AS medicine amount in tigecycline is only 56.5-76.9% of the effective antibacterial medicine amount in vivo.
The revised "tigecycline for injection" at month 11 of 2021 suggests that a single administration of 300mg in healthy volunteers could result in an increased incidence of nausea and vomiting, whereas the effective amount of anti-AS in the present invention was only 18.8-25.6% of the increased dose for clinical adverse reactions.
The dosage of the invention in the body of the mice is 10mg/kg, which is lower than the LD50 value of the mice by 98-124mg/kg, and the safe range of the medicine use is large.
At present, the study reports that the statin drugs have the main effects of reducing blood fat, and on the aspect of resisting AS plaque, the effect of slightly reducing atheromatous plaque can be achieved only by continuously taking the drugs for more than 6 months. In animal experiments, the atheromatous plaque accounts for about 7% of the area of the lumen after 1 month of the use of the tigecycline, and compared with the atheromatous plaque of a control group without the use of the tigecycline, the atheromatous plaque has obvious effect of slowing down and reducing the atheromatous plaque (figure 9).
Summarizing:
in the specific embodiment of the invention, the tigecycline has the effects of strongly inhibiting oxLDL induced macrophage foaming, reducing inflammatory reaction of the cells, promoting autophagy of the foamed macrophages and inhibiting migration of the foamed macrophages.
Based on the fact that atherosclerosis is a process that macrophages, endothelial cells and smooth muscle cells in blood vessels are stimulated by chronic inflammation and atheromatous plaques are slowly formed in blood vessels, according to the invention, through in vitro cell experiments and in vivo animal experiment results, the tigecycline can inhibit macrophage foaming and inflammatory processes in AS processes, promote macrophage autophagy, slow AS plaque formation, eliminate AS plaques, and prove that tigecycline is used AS a novel medicine for resisting AS plaque formation and eliminating plaques.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above-described embodiments, which are merely illustrative and not restrictive, and many forms may be made by those having ordinary skill in the art without departing from the spirit of the present invention and the scope of the claims, which are to be protected by the present invention.
Claims (10)
1. Use of tigecycline for the manufacture of a medicament for preventing and eliminating atherosclerotic plaques, characterized in that the tigecycline is used for preventing formation of atherosclerotic plaques on an arterial intima and/or eliminating atherosclerotic plaques already formed on an arterial intima.
2. The use of claim 1, wherein tigecycline is used to inhibit phagocytosis of oxidized low density lipoprotein cholesterol by macrophages to form foam cells.
3. The use according to claim 2, wherein the tigecycline is used to inhibit macrophage phagocytic oxidation of low density lipoprotein cholesterol function at a half maximal effector concentration of less than 2 μg/ml.
4. The use of claim 1, wherein the medicament is prepared in dosage unit form, formulated as a single use, individual dosage form containing 50-80mg of tigecycline, and formulated as a single dosage unit in 30 individual dosage forms.
5. The use according to claim 4, wherein the pharmaceutical dosage form comprises an injection, an oral solution and/or a tablet; pharmaceutically acceptable carriers and/or adjuvants may also be included in the medicament.
6. Application of tigecycline in preparing medicine for regulating and controlling macrophage phagocytic oxidation of low density lipoprotein cholesterol.
7. The use according to claim 6, wherein tigecycline acts on macrophages phagocytosed oxidized low density lipoprotein cholesterol; inhibiting expression of a proinflammatory factor within the macrophage; alternatively, the expression of inflammatory factors within the macrophage is promoted.
8. The use according to claim 6, wherein tigecycline acts on macrophages phagocytosed oxidized low density lipoprotein cholesterol; down-regulating phosphorylated protein levels in NF- κb signaling pathway and PI3K/AKT/mTOR signaling pathway.
9. The use according to claim 6, wherein tigecycline acts on macrophages phagocytosed oxidized low density lipoprotein cholesterol; down-regulating expression of an autophagic protein in said macrophage; alternatively, inhibiting autophagy protein expression in the macrophage is upregulated.
10. The use of claim 6, wherein tigecycline is used to inhibit cell migration of vascular smooth muscle.
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CN103893200A (en) * | 2012-12-26 | 2014-07-02 | 中国医学科学院药用植物研究所 | Applications of cordycepin used for preparation of medicines used for preventing and treating atherosclerosis |
CN105561297A (en) * | 2016-01-15 | 2016-05-11 | 中国人民解放军第二军医大学 | Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis |
CN109908163A (en) * | 2019-03-25 | 2019-06-21 | 哈尔滨医科大学 | Application of the geraniin in preparation prevention or treatment atherosclerosis drug |
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CN103893200A (en) * | 2012-12-26 | 2014-07-02 | 中国医学科学院药用植物研究所 | Applications of cordycepin used for preparation of medicines used for preventing and treating atherosclerosis |
CN105561297A (en) * | 2016-01-15 | 2016-05-11 | 中国人民解放军第二军医大学 | Application of macrophage beta-profilin-1 to preparation of drug for preventing or treating atherosclerosis |
CN109908163A (en) * | 2019-03-25 | 2019-06-21 | 哈尔滨医科大学 | Application of the geraniin in preparation prevention or treatment atherosclerosis drug |
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