Steady-state magnetic field prevention and treatment system and application thereof in prevention and treatment of atherosclerosis

Abstract

The invention discloses a steady-state magnetic field prevention and treatment system and application thereof in atherosclerosis prevention and treatment, and relates to the technical field of biological medicine, the system comprises a magnetic plate formed by splicing 9 (3 * 3) homopolar neodymium iron boron particle permanent magnets, and a steady-state magnetic field with the strength of 0.01-150 mT in the vertical direction can be generated in a working area. The application of the magnetic plate comprises the following steps: placing an atherosclerosis model animal ApoE / mouse above the magnetic plate for continuous magnetic field exposure, and feeding with high-fat feed for 24 weeks to construct an animal model for research. Experimental results show that a 150mT steady-state magnetic field (especially in the upward direction) can significantly reduce the increase of the area of aortic plaques induced by high fat diet, and can reduce the abnormally increased Fe and total iron levels in serum. The invention provides a non-invasive physical intervention means which is simple to operate and has no drug side effect, and provides a new experimental tool and method for mechanism research of atherosclerosis.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically a steady-state magnetic field prevention and control system and its application in the prevention and control of atherosclerosis. Background Technology

[0002] Atherosclerosis is an arterial wall disease characterized by lipid deposition, fibrosis, and calcium deposition in the arterial intima. It is often caused by factors such as dyslipidemia, hypertension, and smoking. In the early stages, it manifests as fatty streaks, which then develop into fibrous plaques and complex lesions. It can lead to arterial stenosis and occlusion, causing serious consequences such as cardiovascular and cerebrovascular diseases. It is the pathological basis of many cardiovascular and cerebrovascular diseases.

[0003] Existing methods for the prevention and treatment of atherosclerosis include drug therapy, lifestyle modifications, and surgical treatment. Drug therapy mainly uses antihypertensive drugs, lipid-lowering drugs, and antiplatelet aggregation drugs. These drugs need to be taken long-term, may have certain side effects, and require regular monitoring of relevant indicators. Lifestyle modifications include quitting smoking, limiting alcohol consumption, controlling weight, maintaining a balanced diet, and regular exercise. These measures require long-term adherence, and their effectiveness varies from person to person. Surgical treatments, such as endarterectomy or arterial stenting, are suitable for severe arterial stenosis, but the surgery carries high risks, and long-term medication and regular follow-up may be required post-operatively. Existing methods may have shortcomings and inconveniences in terms of precision, non-invasiveness, and patient compliance.

[0004] Magnetic fields, as a non-invasive physical intervention, are beginning to show promise in the treatment of certain diseases. For example, transcranial magnetic stimulation (TMS) using pulsed magnetic fields has been approved in several countries, including the United States, for the treatment of obsessive-compulsive disorder, migraines, and depression. Compared to pulsed magnetic fields, steady-state magnetic fields are simpler to operate, more affordable, have no thermal effects, and fewer side effects. Summary of the Invention

[0005] To address the shortcomings of existing approaches to the prevention and treatment of atherosclerosis, this invention provides a steady-state magnetic field prevention and treatment system and its application in the prevention and treatment of atherosclerosis. This solves the problems of existing technologies, such as the lack of regulation of atherosclerosis progression through steady-state magnetic fields and the deficiencies in atherosclerosis prevention and treatment methods, including drug side effects, poor long-term compliance, and high surgical risks.

[0006] The present invention solves the above-mentioned technical problems through the following technical means:

[0007] The present invention first provides a steady-state magnetic field prevention system, including a magnetic field generating device, which includes a magnetic plate; the magnetic plate is composed of 9 (3×3) identical neodymium iron boron granular permanent magnets spliced ​​together, the magnetic field of the spliced ​​magnetic plate is in the vertical direction, and a cage containing a mouse is placed directly on the spliced ​​magnetic plate, the magnetic field strength of the magnetic plate at the location of the mouse is about 0.01-150mT.

[0008] The present invention also provides an application of a steady-state magnetic field prevention system in the prevention and treatment of atherosclerosis, specifically including the following steps:

[0009] (1) Constructing a mouse model of atherosclerosis: ApoE ⁻ / ⁻ Mice were placed directly above a magnetic plate for magnetic exposure and fed a high-fat diet (21% fat, 0.15% cholesterol) for 24 weeks. The mice were sacrificed at the end of the experiment for further analysis.

[0010] (2) Oil red oxygen staining of mouse aorta: The isolated aorta was fixed overnight in 4% paraformaldehyde, then longitudinally cut and fixed on the surface of black wax block. After 10 min of oil red oxygen staining, the staining solution was discarded, and the aorta was differentiated in 70% ethanol, washed, and photographed. The area of ​​AS plaque was calculated using ImageJ software, and the result was expressed as: plaque area / total aortic intima area × 100%.

[0011] (3) Detection of four lipid items in mouse serum: Collect mouse serum and detect the four lipid items in the serum according to the kit instructions.

[0012] (4) Detection of Fe²⁺ and total iron levels in mouse serum: Collect mouse serum and detect the Fe²⁺ and total iron levels in the serum according to the kit instructions.

[0013] (5) Detection of Fe²⁺ and total iron levels in mouse liver: The mouse livers frozen at -80℃ were thawed on ice, and then the Fe²⁺ and total iron levels in the tissues were detected according to the kit instructions.

[0014] The present invention has the following advantages:

[0015] This invention employs a purely physical steady-state magnetic field for intervention, eliminating the need for exogenous chemical substances and avoiding drug-related metabolic burdens and potential toxic side effects, thus providing a safer intervention approach. It is simple to operate, easy to implement and maintain, and conducive to improving compliance: the system structure of this invention is simple (consisting only of magnetic plates), requiring only the animal to be placed in the magnetic field environment, without complex operations or behavioral constraints, greatly reducing the difficulty of implementation and facilitating long-term, stable intervention research; as a non-invasive physical prevention research tool, it completely avoids surgical trauma, anesthesia risks, and expensive postoperative maintenance, providing a low-risk, low-cost technical means for exploring the prevention and treatment mechanisms of atherosclerosis in the preclinical research stage.

[0016] This invention demonstrates a clear interventional effect on the pathological aspects of atherosclerosis: Experiments have confirmed that a steady-state magnetic field of specific intensity (e.g., 150 mT) and direction (especially upward) can significantly reduce the increase in aortic plaque area induced by a high-fat diet, and simultaneously reduce abnormally elevated levels of Fe²⁺ and total iron in serum. This indicates that the invention not only acts on morphological plaques but may also exert its effects by regulating iron metabolism disorders closely related to atherosclerosis, providing a new, mechanism-targeted physical intervention platform for disease research.

[0017] This invention clarifies a standardized research method that combines the specific physical parameters (intensity and direction) of a steady-state magnetic field with the construction and evaluation of animal models of atherosclerosis. This fills the gap in existing technologies regarding the lack of research methods for regulating disease progression through steady-state magnetic fields, and opens up a new and reproducible experimental pathway for exploring the application of physical factors in the prevention and treatment of cardiovascular diseases. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the mouse magnetization process in an embodiment of the present invention.

[0019] Figure 2 This is a comparison of the results of oil red oxygen staining of the mouse aorta in an embodiment of the present invention.

[0020] Figure 3 This is a statistical chart showing the results of four serum lipid tests in mice in this embodiment of the invention.

[0021] Figure 4 This is a statistical chart showing the results of iron ion level detection in mouse serum and liver in an embodiment of the present invention.

[0022] In the diagram: 1. Magnetic plate; 2. Neodymium iron boron permanent magnet. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0024] Unless otherwise specified, all experimental materials and reagents used in the following examples were obtained commercially. All animal experiments were conducted in accordance with relevant ethical guidelines and approved by the Laboratory Animal Ethics Committee.

[0025] Example 1: This example provides a steady-state magnetic field control system, such as... Figure 1 As shown, a magnetic field generating device is included, which comprises a magnetic plate 1. As a specific implementation, reference can be made to the magnetic particle splicing structure disclosed in Chinese Patent No. CN113117241B. Specifically, the magnetic plate 1 is composed of nine (3×3) identical neodymium iron boron particle permanent magnets 2 spliced ​​together, and the magnetic field direction of the spliced ​​magnetic plate 1 is vertical; when a cage containing a mouse is placed directly on the spliced ​​magnetic plate 1, the magnetic field strength of the magnetic plate 1 at the location of the mouse is approximately 0.01-150 mT.

[0026] Example 2 discloses the effects of a steady-state magnetic field on plaque area, blood lipid levels, and Fe²⁺ and iron in serum and liver of a mouse model of atherosclerosis.

[0027] 1. Experimental Animals and Grouping: Mice were placed above the aforementioned magnetic field device, and the magnetic field applied to the mice was adjusted to approximately 0.01-150 mT. All experimental protocols were ethically approved. SPF-grade 6-week-old male ApoE mice were used. ⁻ / ⁻ Mice were acclimatized in an SPF-grade animal facility for one week, and then randomly divided into a control group (ND), a high-fat diet group (HFD), a high-fat diet N-pole magnetic field treatment group (HFD+N), and a high-fat diet S-pole (HFD+S) magnetic field treatment group. Each group was given an acclimatized diet, while the high-fat diet (21% fat, 0.15% cholesterol) was fed 24 hours a day for 24 consecutive weeks.

[0028] 2. Mouse aortic oil red oxygen staining: After the experiment, the mouse aorta was dissected and peeled, then fixed overnight in 4% paraformaldehyde. The aorta was washed with PBS, cut open, and fixed onto a black paraffin plate, then stained with 0.3% oil red oxygen (Sigma, 1320-06-5) in the dark for 20 minutes. The oil red oxygen was discarded, and the aorta was differentiated three times with 70% ethanol, washed, and photographed. The AS plaque area was calculated using ImageJ software, and the result is expressed as: plaque area / total aortic intima area × 100%.

[0029] 3. Detection of four lipid parameters in mouse serum: After the experiment, blood samples were obtained by enucleation. After standing, the samples were centrifuged at 4℃ and 12000 rpm for 20 minutes, and the supernatant serum was collected. The levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol in the serum were detected using Elabscience E-BC-K261-M, Elabscience E-BC-K221-M, Elabscience E-BC-K205-M, and Elabscience E-BC-K109-M, respectively. The detection procedures were strictly performed according to the instructions of each kit.

[0030] 4. Detection of ferric and ferrous ion levels in mouse serum: After the experiment, blood samples were obtained by enucleation. After standing, the samples were centrifuged at 12000 rpm at 4℃ for 20 min, and the supernatant serum was collected. The levels of ferric and ferrous ions in the serum were detected using the Beyotime Ferric and Ferrous Ion Detection Kit (S1066S).

[0031] 5. Detection of ferric and ferrous ion levels in mouse liver tissue: After the experiment, mouse liver tissue was obtained. 50 mg of liver tissue was weighed, cut into small pieces, and added to the extraction solution at a ratio of 1:10. The mixture was then ground on ice and centrifuged at 12000 rpm for 20 min at 4℃. The supernatant serum was collected. The levels of ferric and ferrous ions in the serum were detected using the Beyotime Ferric and Ferrous Ion Detection Kit (S1066S).

[0032] Experimental results

[0033] 1. For example Figure 2 As shown, mice on a high-fat diet for 6 months had a significantly larger aortic plaque area than mice on a normal diet; while a steady-state magnetic field of 150 mT could reduce the increase in aortic plaque area induced by a high-fat diet, with the upward steady-state magnetic field being particularly significant.

[0034] 2. For example Figure 3 As shown, a high-fat diet for 6 months can increase ApoE levels. ⁻ / ⁻ In mice, total cholesterol, low-density lipoprotein, and triglyceride levels were decreased, while high-density lipoprotein levels were reduced due to ApoE. ⁻ / ⁻Mice can spontaneously develop atherosclerosis, therefore there was no statistically significant difference between the high-fat diet group and the normal diet group.

[0035] 3. For example Figure 4 As shown, a high-fat diet for 6 months can increase ApoE levels. ⁻ / ⁻ The levels of iron in the serum and liver of mice showed the most significant increase in Fe²⁺ levels. Treatment with steady-state magnetic fields in two different directions (upper and lower) could significantly reduce the increase in serum Fe²⁺ and total iron levels induced by a high-fat diet, but this reduction effect was not observed in the liver.

[0036] The above experimental results confirm that the steady-state magnetic field prevention and control system provided by this invention can be effectively applied to the study of atherosclerosis, and shows a clear effect in reducing plaque burden and regulating serum iron metabolism.

[0037] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A steady-state magnetic field prophylactic system, characterized by, The application relates to a steady magnetic field prevention and treatment system, which comprises a magnetic field generating device, wherein the magnetic field generating device comprises a magnetic plate (1) which is composed of a plurality of neodymium-iron-boron particle permanent magnets (2) with the same magnetization direction arranged in an array form, and is used for generating a steady magnetic field with a vertical direction and a strength of 0.01-150 mT in a working area.

2. The steady magnetic field prevention system according to claim 1, characterized by, The number of the neodymium-iron-boron particle permanent magnets (2) is 9, and the array is spliced into the magnetic plate (1) in a 3-row and 3-column array form.

3. The steady magnetic field prevention system according to claim 1 or 2, characterized by, The system is used for constructing an animal model for atherosclerosis research.

4. The steady magnetic field prevention system according to claim 3, wherein The animal model is constructed by using ApoE- / - mice.

5. Application of the steady magnetic field prevention and treatment system in claim 1 in preparation of experimental devices for atherosclerosis research.

6. Use according to claim 5, characterized in that, The application comprises continuously exposing atherosclerosis model animals to a magnetic field by using the steady magnetic field prevention and treatment system.

7. Use according to claim 6, characterized in that, The atherosclerosis model animal is ApoE ⁻ / ⁻ mice, and the application further comprises feeding the mice with high-fat diet while exposed to the magnetic field; the high-fat diet has a fat content of 21% and a cholesterol content of 0.15%.

8. Use according to claim 7, characterized in that, The application comprises obtaining aorta tissues of the subject after the magnetic field exposure is ended, and detecting a plaque area of the aorta tissues by oil red O staining, so as to evaluate the development of atherosclerosis.

9. Use according to claim 7, characterized in that, The application comprises detecting blood lipid levels and iron ion and ferrous ion levels in serum, so as to evaluate the development of atherosclerosis and the iron metabolism state.

10. Use according to claim 7, characterized in that, The application comprises detecting iron ion and ferrous ion levels in liver tissues, so as to evaluate the influence of the magnetic field on the whole body iron metabolism.

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