Use of p-methoxybenzyl alcohol in preparing a drug for promoting arterial plaque stabilization

Abstract

The present invention belongs to the field of biomedicine technology, and specifically relates to the use of p-methoxybenzyl alcohol for preparing a drug that promotes the stability of arterial plaques. The present invention shows that p-methoxybenzyl alcohol can regulate blood lipids and liver levels and regulate the relative strength of vulnerable components and stabilizing factors in plaques, which is specifically manifested in reducing serum TG, LDL-C, increasing serum HDL-C levels, reducing liver TC, LDL-C levels, reducing lipid content in arterial plaques, increasing collagen content in plaques, and reducing plaque VI values, thereby achieving the effect of promoting the stability of arterial plaques and effectively preventing and treating AS secondary diseases. Compared with similar drugs and treatment methods commonly used in clinical practice, p-methoxybenzyl alcohol has a wide source, low price, and significant efficacy, and has good clinical application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and particularly relates to use of p-methoxybenzyl alcohol in preparing a drug for promoting the stabilization of arterial plaques. Background Art

[0002] Atherosclerosis (AS) is considered to be a disease associated with lipid accumulation and inflammatory response. Abnormal lipid metabolism is an important factor in the occurrence and development of AS and is the initial lesion that triggers AS. Lipid substances such as TC, TG, HDL and LDL have always been used as an important indicator for assessing the risk of AS and have been widely used as key indicators for the prevention and treatment of clinical cardiovascular diseases in the past few decades.

[0003] Reduced plaque stability can lead to AS plaque rupture, and plaque rupture has been recognized as the main cause of acute cardiovascular and cerebrovascular events. Whether a plaque ruptures depends mainly on the vulnerability of the plaque. From the perspective of the distinguishing characteristics of stable plaques and vulnerable plaques, the stability of the plaque depends mainly on the relative strength of the vulnerable components "lipids and inflammatory macrophages" and stabilizing factors such as "collagen and smooth muscle cells" in the plaque. The components of vulnerable plaques are often characterized by high expression of vulnerable components and low and weak stabilizing factors, and are mainly characterized by a large number of inflammatory macrophage infiltration, large plaque lipid cores, few smooth muscle cells, low collagen content, and thin fibrous caps. Therefore, early identification of the characteristics of vulnerable plaques and intervention treatment are important strategies for preventing acute cardiovascular and cerebrovascular events. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. They can competitively inhibit the endogenous cholesterol synthesis rate-limiting enzyme HMG-CoA reductase, block the intracellular hydroxymevalonic acid metabolic pathway, reduce intracellular cholesterol synthesis, and thus feedback stimulate the increase in the number and activity of low-density lipoprotein (LDL) receptors on the cell membrane surface, increase serum cholesterol clearance and reduce levels. In addition to being used for lipid-lowering treatment, statins can also improve endothelial cell function, antioxidant and anti-thrombotic effects, etc., which are beneficial to reduce AS formation or stabilize AS plaques. They have become an effective drug for the prevention and treatment of cardiovascular and cerebrovascular malignant events, but their reduction in the incidence of cardiovascular and cerebrovascular events in randomized controlled trials (RCTs) is still controversial, and their drug tolerance, muscle symptoms and other side effects cannot be ignored. Therefore, it is an important method to prevent secondary diseases of AS to develop effective therapeutic drugs and methods for the formation and rupture mechanism of vulnerable plaques and promote the transformation of plaques to a stable direction.

[0004] 4-Methoxybenzyl alcohol (4-MBA, molecular formula: C8H 10O2) is an important pharmaceutical intermediate, and the existing technology has been studied and found its multiple uses. CN104922095B discloses "the use of p-methoxybenzyl alcohol in the preparation of drugs for preventing or / and treating neuroinflammatory diseases", proving that it has the effect of preventing and treating central nervous system degenerative diseases related to neuroinflammation such as Alzheimer's disease and Parkinson's disease; CN105012280A discloses "the use of p-methoxybenzyl alcohol in the preparation of drugs or health products for preventing or / and treating thrombotic diseases", discussing its role in preventing and treating thrombotic diseases. However, there has been no public report on the pharmacological effect of p-methoxybenzyl alcohol in promoting the stability of arterial plaques. Summary of the invention

[0005] The purpose of the present invention is to solve the defects and shortcomings in the above-mentioned prior art and provide the use of p-methoxybenzyl alcohol for preparing a drug for promoting the stabilization of arterial plaques.

[0006] The present invention provides the use of p-methoxybenzyl alcohol for preparing a medicine for promoting the stabilization of arterial plaques.

[0007] Furthermore, the drug is a drug that can regulate blood lipid and liver lipid levels and the relative strength of vulnerable components and stabilizing factors in plaques;

[0008] Furthermore, the regulation of blood lipid and liver levels is to reduce serum TG, LDL-C levels, increase serum HDL-C levels, and reduce liver TC, LDL-C levels;

[0009] Furthermore, the relative strength of the vulnerable components and stabilizing factors in the plaque is regulated by reducing the lipid content in the arterial plaque, increasing the collagen content in the plaque, and reducing the VI value of the plaque.

[0010] Furthermore, the drug is a drug for preventing and treating secondary diseases of atherosclerosis;

[0011] Furthermore, the drug is a preparation prepared by using p-methoxybenzyl alcohol as an active ingredient and adding pharmaceutically acceptable excipients or auxiliary ingredients;

[0012] Furthermore, the preparation is an oral preparation;

[0013] Furthermore, the preparation is a capsule, granule or tablet.

[0014] The present invention has at least the following beneficial technical effects:

[0015] The drug for promoting arterial plaque stability prepared by p-methoxybenzyl alcohol of the present invention has the effects of significantly reducing serum TG and LDL-C, increasing serum HDL-C levels, reducing liver TC and LDL-C levels, reducing lipid content in arterial plaques, increasing collagen content in plaques, and reducing plaque VI values, thereby achieving the effect of promoting arterial plaque stability, effectively targeting the formation and rupture mechanism of vulnerable plaques, and proposing a new method for promoting the transformation of plaques to a stable direction, providing a new solution for preventing the occurrence of secondary diseases of AS. In addition, compared with similar drugs and treatment methods commonly used in clinical practice, p-methoxybenzyl alcohol has a wide source, low price, significant efficacy, and good clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is the effect of p-methoxybenzyl alcohol on the body weight of AS mice;

[0017] Figure 2 The effect of p-methoxybenzyl alcohol on the wet weight and index of organs in AS mice;

[0018] Figure 3 The effect of p-methoxybenzyl alcohol on the changes of serum lipids in AS mice;

[0019] Figure 4 The effect of p-methoxybenzyl alcohol on the changes of liver fat content in AS mice;

[0020] Figure 5 The effect of p-methoxybenzyl alcohol on the gross plaque formation in the aorta of AS mice;

[0021] Figure 6 The effect of p-methoxybenzyl alcohol on plaque formation in aorta sections of AS mice;

[0022] Figure 7 The effect of p-methoxybenzyl alcohol on lipid content in aortic plaques of AS mice;

[0023] Figure 8 The effect of p-methoxybenzyl alcohol on the content of collagen fibers in aortic plaques of AS mice;

[0024] Fig. 9 The effect of p-methoxybenzyl alcohol on the content of macrophages in aortic plaques of AS mice;

[0025] Fig.10 The effect of p-methoxybenzyl alcohol on the content of smooth muscle cells in aortic plaques of AS mice;

[0026] Fig.11 This is the effect of methoxybenzyl alcohol on the VI value of aortic plaque in AS mice. DETAILED DESCRIPTION

[0027] The present invention is further described below in conjunction with specific examples and the accompanying drawings, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art, and the reagents, raw materials and equipment used are all commercially available.

[0028] 1 Experimental Materials

[0029] 1.1 Experimental animals

[0030] 30 healthy SPF male ApoE- / - mice and 10 C57BL / 6J mice, 6-8 weeks old, weighing 18-22 g, license number: SCXK(Beijing)2019-0010; certificate number: NO.110324231105405644; NO.110324231105404915, all provided by Sibefore (Beijing) Biotechnology Co., Ltd.

[0031] 1.2 High-fat diet

[0032] High-fat feed was purchased from Chengdu Paishanfeike Biotechnology Co., Ltd.;

[0033] High-fat feed formula: in terms of mass percentage, it consists of 40% fat, 25% cholesterol, 0.5% sodium cholate and the remainder basic feed.

[0034] 1.3 Experimental drugs

[0035] p-Methoxybenzyl alcohol

[0036] 1.4 Test substance preparation

[0037] p-Methoxybenzyl alcohol (28 mg / kg): Accurately weigh 28 mg of p-methoxybenzyl alcohol, dissolve it in double distilled water to make up to 10 mL, and store it at 4°C in the dark.

[0038] Simvastatin (10 mg / kg): Accurately weigh 10 mg of ground simvastatin, dissolve it in double distilled water to make up to 10 mL, and store at 4°C in the dark.

[0039] 2 Experimental methods

[0040] 2.1 Animal grouping and drug administration

[0041] After one week of animal adaptive feeding, 10 C57BL / 6J mice were set as the normal group, and 30 ApoE- / - mice were fed a high-fat diet to establish an atherosclerotic plaque model. Two weeks after modeling, the mice with elevated blood lipids but no plaque formation were randomly divided into three groups: the model group, the positive group (simvastatin, 10 mg / Kg), and the p-methoxybenzyl alcohol (28 mg / kg), with 10 mice in each group. Different test samples were gavaged at the beginning, and the normal and model groups were gavaged with equal volumes of solvent (1 time / d), and the gavage volume was 0.1 ml / 10g. Until the end of 12 weeks. During this period, the normal group was given ordinary feed, and the other groups were given high-fat feed.

[0042] 2.2 Sample collection

[0043] After 12 weeks, fast for 12 hours and weigh the body weight. After blood collection, quickly open the chest and abdominal cavities, perform cardiac perfusion with cold saline, and rinse the residual blood in the blood vessels. Use ophthalmic forceps to press the iliac artery-abdominal aorta-thoracic aorta-aortic arch-common carotid artery to peel off the blood vessels. One part was fixed in 4% paraformaldehyde solution for 48 hours, and macroscopic Oil Red O staining was performed, and after dehydration in a dehydrator, paraffin embedding and sectioning were performed for HE staining. The remaining blood vessels were placed in a 2ml centrifuge tube and stored at -80℃. At the same time, the mouse liver was removed, placed in a 10ml centrifuge tube, and stored at -80℃ for later use.

[0044] 2.3 Weight monitoring

[0045] During the experiment, the body weights of mice were weighed and recorded weekly.

[0046] 2.4 Effects of p-methoxybenzyl alcohol on organ wet weight and organ index in AS model mice

[0047] After the animals were killed, the liver, spleen, and kidneys of the mice were quickly removed, and the excess blood was rinsed in ice saline, and then dried with filter paper, and the organ weight was weighed. The formula for calculating the organ index is: Organ index = organ wet weight / animal body weight.

[0048] 2.5 Effect of methoxybenzyl alcohol on serum lipid changes in AS model mice

[0049] After blood was collected from the eyeballs of mice, the blood was centrifuged at 3500rpm / min for 10 minutes to separate the serum. The changes in TG, TC, HDL-C, and LDL-C levels were tested according to the kit requirements. (The model mice were randomly grouped according to the blood lipid status before administration of the test substance)

[0050] 2.6 Effect of p-methoxybenzyl alcohol on changes in liver lipids in AS model mice

[0051] Weigh about 50 mg of mouse liver tissue, add sodium chloride solution at a ratio of 1:9 (i.e., 1 g of liver tissue plus 9 mL of 0.9% sodium chloride solution), grind and centrifuge to separate the supernatant, and detect its TG, TC, HDL-C, and LDL-C according to the requirements of the kit.

[0052] 2.7 Effect of p-methoxybenzyl alcohol on the gross plaque morphology of aorta in AS model mice

[0053] The entire aorta was grossly stained with Oil Red O, and the vascular morphology, texture, plaque location, etc. were observed with the naked eye; the stained aorta was scanned with a scanner, and the ratio of the stained plaque to the entire aorta was calculated using Image software. The calculation formula was: red-stained plaque area / area of ​​the entire aorta. The specific steps are as follows:

[0054] a. Fix the blood vessels for more than 24 hours, remove the peripheral fat, cut open the blood vessels longitudinally, and wash them twice with PBS;

[0055] b. Rinse with tap water for 5 seconds, soak in 60% isopropanol for 3 seconds, and then stain with Oil Red O at 37℃ in the dark for 60 minutes.

[0056] c. Differentiate with 60% isopropanol until the fat plaques are orange-red or bright red and other parts are almost colorless. Wash with distilled water to terminate the differentiation.

[0057] d. After absorbing excess water, place it on a black background board, spread out the blood vessel, place it on the scanner, adjust the scanner exposure, and scan.

[0058] 2.8 Effect of p-methoxybenzyl alcohol on plaque formation in aortic sections of AS model mice

[0059] Part of the aorta was fixed in 4% paraformaldehyde for 48 hours, and stained with hematoxylin and eosin (HE). The vascular tissue pathology was observed under an optical microscope. Image software was used to calculate the ratio of the area of ​​plaques in the aortic slices to the area of ​​the lumen of the vascular slices after staining. The calculation formula was: plaque area / lumen area. The HE staining steps were as follows:

[0060]

[0061]

[0062]

[0063] 2.9 Effect of methoxybenzyl alcohol on lipid content in aortic plaques of AS model mice

[0064] The removed blood vessels were fixed, dehydrated, and embedded in OCT, and then the aortic sections were stained with Oil Red O for observation. Image software was used to calculate the ratio of the area of ​​red-stained lipids in the aortic sections to the area of ​​plaques in the blood vessel sections. The calculation formula was: lipid area / plaque area. The specific steps were as follows:

[0065] a. Take frozen blood vessels at -80℃ and fix them in 4% paraformaldehyde solution for 48 hours;

[0066] b. Gradient dehydration with 20% and 30% sucrose respectively;

[0067] c. Take the tissue and embed it in OCT, cut it into 6 μm slices with a freezing microtome, and stick them on a glass slide;

[0068] Soak in 60% isopropanol for 2 minutes;

[0069] d. Place the slide in a wet box, use a pipette to draw Oil Red O staining solution and drop it onto the slide, staining for 10 minutes;

[0070] e. Differentiate with 75% ethanol for 2 seconds and rinse with distilled water for 1 minute;

[0071] f. Counterstain the cell nucleus with hematoxylin for 2 minutes and rinse with distilled water for 1 minute;

[0072] g. After drying, seal the slides with glycerol gelatin;

[0073] h. Under microscopic observation, cell nuclei are blue, lipid droplets are bright red, and interstitium is colorless.

[0074] Note: Prepare Oil Red O dye solution by adding distilled water in a ratio of 3:2, mix well and filter before use.

[0075] 2.10 Effect of p-methoxybenzyl alcohol on the content of collagen fibers in aortic plaques of AS model mice

[0076] The removed blood vessels were fixed, dehydrated, and embedded in paraffin, and then Masson staining was performed on the aortic sections of the blood vessels. Image software was used to calculate the ratio of the area of ​​collagen fibers in the stained aortic sections to the area of ​​plaques in the blood vessel sections. The calculation formula was: collagen fiber area / plaque area. The specific steps were as follows:

[0077] a. Dewax the paraffin sections to water: put the sections into environmentally friendly dewaxing solution I for 20 minutes, environmentally friendly dewaxing solution II for 20 minutes, anhydrous ethanol I for 5 minutes, anhydrous ethanol II for 5 minutes, and 75% alcohol for 5 minutes, and wash with tap water.

[0078] b. Soak the slices in Masson A solution overnight and rinse with running water;

[0079] c. Slice into a dye solution of Masson B solution and Masson C solution in equal proportions, immerse for 1 minute, wash with tap water, differentiate with differentiation solution for a few seconds, and wash with tap water;

[0080] d. Immerse the slices in Masson D solution for 6 minutes and rinse with tap water;

[0081] e. Dye with Masson E solution for 1 minute;

[0082] f. Without washing, drain slightly and directly put into Masson F solution for dyeing for 2-30 seconds;

[0083] g. The slices were rinsed and differentiated with 1% acetic acid and dehydrated with two cylinders of anhydrous ethanol;

[0084] h. Transparent sealing: Put the slices into the third cylinder of anhydrous ethanol for 5 minutes, xylene for 5 minutes to make them transparent, and then seal the slices with neutral gum;

[0085] j. Microscopy, image acquisition and analysis.

[0086] 2.11 Effect of p-methoxybenzyl alcohol on the content of macrophages in aortic plaques of AS model mice

[0087] The removed blood vessels were fixed, dehydrated, and embedded in paraffin, and the aortic sections were immunohistochemically stained with CD68 antibodies. Image software was used to calculate the ratio of the area of ​​collagen fibers in the stained aortic sections to the area of ​​plaques in the blood vessel sections. The calculation formula was: CD68 positive expression area / plaque area. The specific steps were as follows:

[0088] a. Dewaxing of paraffin sections: sequentially place the sections into environmentally friendly dewaxing solution I for 10 min - environmentally friendly dewaxing solution II for 10 min - environmentally friendly dewaxing solution III for 10 min - anhydrous ethanol I for 5 min - anhydrous ethanol II for 5 min - anhydrous ethanol III for 5 min - distilled water for washing;

[0089] b. Antigen retrieval: After cooling naturally, place the slide in PBS (PH7.4) and wash on a decolorizing shaker for 3 times, 5 minutes each time;

[0090] c. Block endogenous peroxidase: Place the slices in 3% hydrogen peroxide solution and incubate at room temperature in the dark for 25 minutes. Place the slides in PBS (PH7.4) and wash them 3 times on a decolorizing shaker, each time for 5 minutes.

[0091] d. Serum blocking: Add 3% BSA in the tissue circle to evenly cover the tissue and block at room temperature for 30 minutes.

[0092] e. Add primary antibody: Gently shake off the blocking solution, add primary antibody prepared in a certain proportion of PBS on the slices, and incubate the slices flat in a humidified box at 4°C overnight;

[0093] f. Add secondary antibody: Place the slide in PBS (PH7.4) and wash on a decolorizing shaker for 3 times, 5 minutes each time. After the slices are slightly dried, add the secondary antibody (HRP labeled) of the same species as the primary antibody in the circle to cover the tissue and incubate at room temperature for 50 minutes;

[0094] g. DAB color development: Place the slide in PBS (PH7.4) and shake on a decolorizing shaker for 3 times, 5 minutes each time. After the slices are slightly dried, add freshly prepared DAB color development solution in the circle, and control the color development time under a microscope. The positive color is brown-yellow, and the slices are rinsed with tap water to stop the color development;

[0095] h. Re-staining of cell nuclei: Re-stain with hematoxylin for about 3 minutes, wash with tap water, differentiate with hematoxylin differentiation solution for a few seconds, rinse with tap water, blue with hematoxylin blueing solution, and rinse with running water;

[0096] j. Dehydration and sealing: Put the slices into 75% alcohol for 5 minutes, 85% alcohol for 5 minutes, anhydrous ethanol I for 5 minutes, anhydrous ethanol II for 5 minutes, n-butanol for 5 minutes, and xylene I for 5 minutes to dehydrate and make them transparent. Take the slices out of xylene and dry them slightly, then seal them with sealing glue.

[0097] k. Microscopic examination: The results are interpreted under a white light microscope. Hematoxylin stains the cell nucleus in blue, and DAB shows positive expression in brown-yellow.

[0098] 2.12 Effect of p-methoxybenzyl alcohol on the content of smooth muscle cells in aortic plaques of AS model mice

[0099] The removed blood vessels were fixed, dehydrated, and embedded in paraffin, and the aortic sections were immunohistochemically stained with α-SMA antibody. Image software was used to calculate the ratio of the area of ​​collagen fibers in the stained aortic sections to the area of ​​plaques in the blood vessel sections. The calculation formula was: α-SMA positive expression area / plaque area. The specific operation steps were the same as "2.11".

[0100] 2.13 Effect of p-methoxybenzyl alcohol on the stability of aortic plaques in AS model mice

[0101] The vulnerability index (VI) of the plaque was calculated to evaluate the stability of the plaque. The calculation formula is: VI = (C lip +C Mac ) / (C Vsmc +C Col )(C Lip , C Mac , C Vsmc , C Col are the contents of lipids, macrophages, vascular smooth muscle cells and collagen fibers, respectively).

[0102] 3 Data processing

[0103] The data obtained in this experiment were analyzed using Image J software and SPSS26.0 software for statistical analysis. The results were expressed as mean ± standard deviation. Indicates; if the data conform to the normal distribution, the variance homogeneity test is performed, and the variance homogeneity is tested using the LSD method; if the variance is unequal, the Tamhane's test is used; if the data do not conform to the normal distribution, a non-parametric test is used; P < 0.05 is considered statistically significant, and the graph is drawn using GraphPad Prism 8.0.1 software.

[0104] 4 Experimental results

[0105] 4.1 Effect of p-methoxybenzyl alcohol on body weight changes in AS mice

[0106] The results show that as time went on, the weight of mice in each group increased, the weight of mice in the model group increased faster, and the weight growth trend of mice in the normal group and each test group was roughly the same. Figure 1 .

[0107] 4.2 Effects of p-methoxybenzyl alcohol on organ wet weight and organ index in AS model mice

[0108] The results showed that the wet weight of liver, liver index, spleen wet weight and spleen index of mice in the model group were significantly increased compared with those in the normal group, and the difference was statistically significant (P < 0.01, P < 0.001); compared with the model group, the wet weight of liver and liver index of mice in the positive group and p-methoxybenzyl alcohol group showed a downward trend, and the wet weight of spleen in the positive group decreased, and the difference was statistically significant (P < 0.01, P < 0.001). See Table 1 for details. Figure 2 .

[0109] Table 1 Effects of p-methoxybenzyl alcohol on wet weight and index of organs in AS mice ( N=10)

[0110]

[0111] Note: vs Normal, *** P<0.001, ** P<0.01; vs Model, ### P<0.001, ## P<0.01.

[0112] 4.3 Effect of p-methoxybenzyl alcohol on serum lipid changes in AS model mice

[0113] Compared with the normal group, the serum TC, TG, and LDL-C levels of the mice in the model group were significantly increased, and the HDL-C level was significantly decreased (P < 0.001, P < 0.01); compared with the model group, the serum TC, TG, and LDL-C levels of the mice in the positive group were significantly decreased, and the serum TG and LDL-C levels of the mice in the methoxybenzyl alcohol group were decreased, and the HDL-C level was increased, and the difference was statistically significant (P < 0.001, P < 0.01). See Table 2 for details. Figure 3 .

[0114] Table 2 Effects of p-methoxybenzyl alcohol on changes in serum lipids in mice ( N=10)

[0115]

[0116] Note: vs Normal, *** P<0.001, ** P<0.01; vs Model, ### P<0.001, ## P<0.01.

[0117] 4.4 Effect of p-methoxybenzyl alcohol on changes in liver fat content in AS model mice

[0118] The TC, TG, and LDL-C contents in the liver of the mice in the model group were significantly higher than those in the normal group (P < 0.001). Compared with the model group, the TC and LDL-C contents in the liver of the mice in the positive group were significantly decreased, and the difference was statistically significant (P < 0.001, P < 0.01), and the HDL-C content was increased, but the difference was not statistically significant (P > 0.05). The TC and LDL-C contents in the liver of the mice in the methoxybenzyl alcohol group were decreased, and the difference was statistically significant (P < 0.001, P < 0.01), the TG content was decreased, and the HDL-C content was increased. However, the difference was not statistically significant (P > 0.05). See Table 3 for details. Figure 4 .

[0119] Table 3 Effects of p-methoxybenzyl alcohol on changes in liver fat content in AS model mice ( N=10)

[0120]

[0121] Note: vs Normal, *** P<0.001; vs Model, ### P<0.001, ## P<0.01.

[0122] 4.5 Effect of p-methoxybenzyl alcohol on the formation of gross aortic plaque in AS model mice

[0123] The results showed that the aorta of the mice in the normal group was thin and smooth, with no obvious plaque formation. However, the aorta of the mice in the model group was thicker, and the plaque formation increased significantly (P < 0.001); the plaques in the positive group and the p-methoxybenzyl alcohol group were reduced after drug intervention. See Table 4 for details. Figure 5 .

[0124] Table 4 Effects of p-methoxybenzyl alcohol on the formation of macroscopic plaques in mouse aorta ( N=3)

[0125]

[0126] Note: vs Normal, *** P<0.001.

[0127] 4.6 Effect of p-methoxybenzyl alcohol on plaque formation in aortic sections of AS model mice

[0128] The ratio of aortic plaque to lumen area in the model group mice was significantly increased compared with the normal group (P < 0.001); compared with the model group, the ratio of aortic plaque to lumen area in the positive group and p-methoxybenzyl alcohol group mice was reduced accordingly, but the difference was not statistically significant (P > 0.05). See Table 5 for details. Figure 6 .

[0129] Table 5 Effects of p-methoxybenzyl alcohol on plaque formation in aorta sections of AS mice ( N=3)

[0130]

[0131] Note: vs Normal, *** P<0.001.

[0132] 4.7 Effect of p-methoxybenzyl alcohol on lipid content in aortic plaques of AS model mice

[0133] The results showed that the lipid content in the aortic plaques of mice in the model group was significantly higher than that in the normal group (P < 0.01); compared with the model group, the lipid content in the aortic plaques of mice in the positive group and the p-methoxybenzyl alcohol group was significantly lower, and the difference was statistically significant (P < 0.05). See Table 6 for details. Figure 7 .

[0134] Table 6 Effects of p-methoxybenzyl alcohol on lipid content in aortic plaques of AS mice ( N=3)

[0135]

[0136] Note: vs Normal, **P<0.01; vs Model, # P<0.05.

[0137] 4.8 Effect of p-methoxybenzyl alcohol on the content of collagen fibers in aortic plaques of AS model mice

[0138] The results show that the content of collagen fibers in the aortic plaques of mice in the model group was significantly lower than that in the normal group (P < 0.001); compared with the model group, the content of collagen fibers in the aortic plaques of mice in the p-methoxybenzyl alcohol group was significantly increased, and the difference was statistically significant (P < 0.05.), and the content of collagen fibers in the plaques of mice in the positive group also tended to increase, but the difference was not statistically significant (P > 0.05). See Table 7 for details. Figure 8 .

[0139] Table 7 Effect of p-methoxybenzyl alcohol on the content of collagen fibers in aortic plaques of AS mice ( N=3)

[0140]

[0141] Note: vs Normal, *** P<0.001; vs Model, # P<0.05.

[0142] 4.9 Effect of methoxybenzyl alcohol on the content of macrophages in aortic plaques of AS model mice

[0143] The results show that the content of macrophages in the aortic plaques of mice in the model group was significantly higher than that in the normal group (P < 0.001); compared with the model group, the content of macrophages in the aortic plaques of mice in the positive group was reduced, and the difference was statistically significant (P < 0.05.), and the content of macrophages in the aortic plaques of mice in the methoxybenzyl alcohol group also tended to decrease, but the difference was not statistically significant (P > 0.05). See Table 8 for details. Fig. 9 .

[0144] Table 8 Effect of p-methoxybenzyl alcohol on the content of macrophages in aortic plaques of AS mice ( N=3)

[0145]

[0146] Note: vs Normal, *** P<0.001; vs Model, # P<0.05.

[0147] 4.10 Effect of p-methoxybenzyl alcohol on the content of smooth muscle cells in aortic plaques of AS model mice

[0148] The results showed that the content of smooth muscle cells in the aortic plaques of mice in the model group was significantly reduced (P < 0.001); compared with the model group, the content of smooth muscle cells in the aortic plaques of mice in the positive group and the p-methoxybenzyl alcohol group was increased, but the difference was not statistically significant (P > 0.05). See Table 9 for details. Fig.10 .

[0149] Table 9 Effect of p-methoxybenzyl alcohol on the content of smooth muscle cells in aortic plaques of AS mice ( N=3)

[0150]

[0151] Note: vs Normal, *** P<0.001.

[0152] 4.11 Effect of p-methoxybenzyl alcohol on the stability of aortic plaques in AS model mice

[0153] The results showed that although there were tiny plaques in the mice of the normal group, their VI values ​​were small and the plaques were relatively stable; the VI values ​​of the plaques in the mice of the model group were significantly higher than those in the normal group (P < 0.001); compared with the model group, the VI values ​​of the plaques in the positive group and the p-methoxybenzyl alcohol group were relatively lower, and the difference was statistically significant (P < 0.001, P < 0.05). See Table 10 for details. Fig.11 .

[0154] Table 10 Effects of p-methoxybenzyl alcohol on VI value of aortic plaque in AS mice ( N=3)

[0155]

[0156] Note: vs Normal, *** P<0.001; vs Model, ### P<0.001, # P<0.05.

[0157] In summary, the p-methoxybenzyl alcohol of the present invention can stabilize AS plaques by regulating changes in blood lipid and liver lipid levels, increasing the content of collagen fibers, a stable component, and reducing the content of lipids, a vulnerable component.

[0158] The above-mentioned embodiments only express the specific implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the protection scope of the present application. It should be pointed out that, for ordinary technicians in this field, several adjustments and improvements can be made without departing from the technical solution concept of the present application, and these all belong to the protection scope of the present application.

Claims

1. Use of p-methoxybenzyl alcohol in the preparation of a drug for promoting the stabilization of atherosclerotic plaques, characterized in that: In the drug, p-methoxybenzyl alcohol is the only active ingredient.

2. The use according to claim 1, characterized in that: The drug is a drug for regulating blood lipid and liver levels.

3. The use according to claim 1, characterized in that: The drug is a drug that adjusts the relative strength of vulnerable components and stabilizing factors in plaques.

4. The use according to claim 2, characterized in that: The drug regulates blood lipid levels by lowering serum TG and LDL-C and increasing serum HDL-C levels.

5. The use according to claim 2, characterized in that: The drug regulates liver levels by reducing liver TC and LDL-C levels.

6. The use according to claim 3, characterized in that: The drug regulates the relative strength of vulnerable components and stabilizing factors in the plaque to reduce the lipid content in the arterial plaque, increase the collagen content in the plaque, and reduce the plaque vulnerability index.

7. The use according to claim 1, characterized in that: The medicine is a preparation prepared by taking p-methoxybenzyl alcohol as the only active ingredient and adding pharmaceutically acceptable excipients or auxiliary ingredients.

8. The use according to claim 7, characterized in that: The preparation is an oral preparation.

9. The use according to claim 8, characterized in that: The oral preparations are capsules, granules and tablets.

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