Application of target drug in resisting atherosclerosis
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An atherosclerosis and drug technology, applied in the field of biomedicine, to achieve the effects of large market prospects and economic value, less toxic and side effects, and a wide range of sources
Pending Publication Date: 2021-10-08
SOUTHERN MEDICAL UNIVERSITY
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After searching by authoritative organizations, it was found that tangerine has anti-inflammatory activity, anti-cancer, hypoglycemic and other biological activities, but there is no research on the anti-atherosclerotic activity of tangerine, especially in stabilizing atherosclerotic plaques. see reports
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Embodiment 1
[0051] Pharmacodynamic experiment of tangerine against atherosclerosis.
[0052] (1) Intervention in groups and recording body weight
[0053] ApoE - / - The mice were randomly divided into a model group (Model), a low-dose intervention group of tangerine (L-NOB, 50mg / kg / d), a medium-dose intervention group of tangerine (M-NOB, 100mg / kg / d), Tangerine high-dose intervention group (H-NOB, 200 mg / kg / d), positive drug group (simvastatin, 10mg / kg / d), were fed with high-fat feed (formula: 0.15% cholesterol, 21% Fat), the oral feeding intervention method was adopted for 24 consecutive weeks, and the body weight changes of the mice were tracked at any time during the intervention. For specific interventions, see figure 1 .
[0054] figure 2 Body weight change curves of mice in each group. As shown in the figure, the initial weight of the mice in each group was concentrated at about 24 g, and there was no statistical difference; the trend of the weight change of the mice in each g...
Embodiment 2
[0066] Molecular mechanism of tangerine against atherosclerosis.
[0067] (1) Detection of key proteins and genes by immunoblotting and real-time fluorescence quantitative method
[0068] Western blotting: Take mouse arterial tissue, add magnetic beads, 50 μL / well of cell lysate containing protease inhibitors, centrifuge at low temperature and low speed for 5 minutes, take the supernatant to obtain total protein, use BCA method to measure protein concentration, and perform protein quantification. Take 50 μg of total protein, separate by 12% SDS polyacrylamide gel electrophoresis, electrotransfer to PVDF membrane (polyvinylidene fluoride membrane), block with 5% skimmed milk (containing 0.1% Tween 20) for 1 hour, add antibody, Incubate overnight at 4°C (β-actin as a control); wash the membrane 3 times with TBS-T, 10 min each time; add horseradish peroxidase (HRP)-labeled secondary antibody, incubate at room temperature for 1 h, rinse with washing solution (TBS- T) Wash the mem...
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Abstract
The invention discloses application of a target drug in resisting atherosclerosis. The application comprises the following steps of: taking a mitochondrial autophagy signal channel mediated by nobiletin PINK1 / Parkin as a drug target; and / or taking an NLRP3 inflammasome signal channel as a drug target. According to the invention, with the application of the nobiletin, the blood fat level of atherosclerosis can be significantly reduced; the plaque structure can be significantly improved; the plaque stability can be improved; the inflammatory reaction can be inhibited; the nobiletin uses the mitochondrial autophagy signal channel mediated by the PINK1 / Parkin as the drug target; and / or, the NLRP3 inflammasome signal channel is used as the drug target; the nobiletin can be used as the effective tool for stabilizing the arteriosclerosis plaque, and provides the foundation for the development of the arteriosclerosis prevention and treatment drug; and in addition, the nobiletin is derived from the natural plant, has characteristics of wide source, low toxic-side effect, and anti-atherosclerosis effect, and has great market prospects and economic values.
Description
technical field [0001] The invention belongs to the field of biomedicine, and relates to a medicinal application of polymethoxyflavone, specifically, tangerine (3',4',5,6,7,8-hexamethoxyflavone) as PINK1 / Application of Parkin-mediated mitophagy and NLRP3 inflammasome signaling pathway target site drugs in anti-atherosclerotic drugs. Background technique [0002] Atherosclerosis is a chronic disease caused by multiple factors. It is the most common and dominant cardiovascular disease. It is also the most critical pathogenic factor and pathological basis for coronary heart disease, cerebral infarction, aortic aneurysm and peripheral blood vessels. It has become one of the greatest threats to human health. Inflammasome is an important part of non-specific immunity, and its activation is one of the core processes of inflammatory response. In recent years, researchers have discovered that inflammasomes are closely related to atherosclerosis. At present, most inflammasomes are...
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