Application of gastrodin in preparation of medicine for regulating PCSK9 and LDLR expression

Abstract

The invention discloses application of gastrodin in preparation of a medicine for regulating and controlling expression of PCSK9 and LDLR (Low-Density Lipoprotein Receptor). Research finds that gastrodin can effectively inhibit PCSK9 expression by adjusting a PCSK9 transcription factor and enhance LDLR expression at the same time. The regulating effect not only is beneficial to improving abnormal lipid metabolism conditions, but also has positive significance on health maintenance of cardiovascular systems, prevention and treatment of liver diseases and the like. The characteristics of gastrodin provide a new direction for the development of novel medicines, and are expected to bring new breakthrough for the treatment and prevention of related diseases.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and particularly relates to the use of gastrodin in preparing drugs for inhibiting PCSK9 expression and / or enhancing LDLR expression. Background Art

[0002] Proprotein convertase subtilisin / kexin type 9 (PCSK9) plays a key role in physiological processes such as human lipid metabolism. PCSK9 can specifically recognize and bind to the low-density lipoprotein receptor (LDLR) on the cell membrane surface, and after forming a complex, it is internalized by the cell. Under the action of lysosomes, LDLR is degraded, resulting in a decrease in the abundance of LDLR on the cell membrane surface. Changes in LDLR abundance will affect the cell's uptake of low-density lipoprotein, thereby causing an imbalance in lipid transport and metabolism in the body, leading to a series of health problems. Existing studies have shown that regulating the expression levels of PCSK9 and LDLR is of great significance for maintaining lipid balance in the body, ensuring the health of the cardiovascular system, and preventing and treating liver diseases.

[0003] As a traditional Chinese medicine, Gastrodia elata Bl. has a long history of application and has shown certain potential in the treatment of various diseases. Gastrodin is the main bioactive component of Gastrodia elata, which has multiple effects such as anti-inflammatory and antioxidant. At present, gastrodin is widely used in the treatment of neurological diseases, but its role in regulating the expression of PCSK9 and LDLR has not been fully studied and applied. Summary of the invention

[0004] The purpose of the present invention is to provide an application of gastrodin in the preparation of a drug for regulating the expression of PCSK9 and LDLR.

[0005] In order to achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: the use of gastrodin in the preparation of drugs for regulating the expression of proprotein convertase subtilisin 9 and low-density lipoprotein receptor.

[0006] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: the use of gastrodin in the preparation of a drug for inhibiting the expression of proprotein convertase subtilisin 9.

[0007] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: the use of gastrodin in the preparation of a drug for enhancing the expression of low-density lipoprotein receptors.

[0008] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: a drug for inhibiting the expression of proprotein convertase subtilisin 9, comprising gastrodin.

[0009] To achieve the above-mentioned purpose and other related purposes, the technical solution provided by the present invention is: a drug for enhancing the expression of low-density lipoprotein receptor, comprising gastrodin.

[0010] The preferred technical solution is: the drug is a single active ingredient gastrodin, or is a combination of gastrodin and excipients.

[0011] The preferred technical solution is: the auxiliary material is simvastatin, atorvastatin or rosuvastatin.

[0012] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0013] This invention reveals for the first time the significant effect of gastrodin on inhibiting PCSK9 expression and enhancing LDLR expression. Through in vivo experiments to establish relevant disease models and in vitro studies using Huh7 cells, it was found that gastrodin can regulate PCSK9 transcription factors, inhibit PCSK9 expression, and enhance LDLR expression. This regulatory mechanism has many positive effects: in terms of lipid metabolism, it helps to improve the transport and metabolism of lipids in the body and reduce the abnormal accumulation of lipids in the blood and tissues; in terms of the cardiovascular system, it reduces the risk of cardiovascular diseases caused by lipid metabolism disorders and plays a protective role in the cardiovascular system; in terms of liver health, it reduces liver damage caused by lipid overload and helps maintain normal liver function. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The results of the effect of gastrodin on the expression of PCSK9 and LDLR in Huh7 cells at the protein level in Example 1 of the present invention are shown.

[0015] Figure 2 The results of the effect of gastrodin on the expression of PCSK9 and LDLR in Huh7 cells at the mRNA level in Example 2 of the present invention are shown.

[0016] Figure 3 The results of Example 3 of the present invention showing that gastrodin inhibits the secretion of PCSK9 in Huh7 cells and enhances the ability of Huh7 cells to take up LDL.

[0017] Figure 4 The results of the effect of gastrodin on the wet weight of liver and liver index of related disease model animals in Example 4 of the present invention are shown.

[0018] Figure 5 The results show the regulatory effect of gastrodin in Example 5 of the present invention on lipid accumulation in related disease model animals.

[0019] Figure 6The results of the effect of gastrodin on lipid accumulation (liver morphology, liver lobule structure and red lipid droplets) in the liver of relevant disease model animals in Example 6 of the present invention are shown.

[0020] Figure 7 The results of the effect of gastrodin in Example 7 of the present invention on reducing lipid accumulation (triglyceride TG, total cholesterol TC, free fatty acid FFA) in the liver of related disease model animals are shown.

[0021] Figure 8 The results show that the gastrodin in Example 8 of the present invention improves related disease conditions by regulating the PCSK9 / LDLR signaling pathway in vivo.

[0022] Fig. 9 The results of the in vivo experiment in Example 9 of the present invention show the effect of gastrodin on the expression of PCSK9 and LDLR at the mRNA level.

[0023] Fig.10 The results of the inhibitory effect of gastrodin on the secretion of PCSK9 in Example 10 of the present invention are shown. DETAILED DESCRIPTION

[0024] The following is a description of the implementation of the present invention by means of specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in the embodiments.

[0025] See also Figure 1-10 . It should be noted that the structures, proportions, sizes, etc. illustrated in the drawings of this specification are only used to match the contents disclosed in the specification for people familiar with this technology to understand and read, and are not used to limit the limiting conditions under which the present invention can be implemented. Therefore, they have no technical substantive significance, and any structural modification, change in proportional relationship or adjustment of size. The following examples are provided for a better understanding of the present invention, but are not intended to limit the present invention. Unless otherwise specified, the experimental materials used in the following examples were purchased from conventional consumables and biochemical reagent stores.

[0026] The present invention mainly proposes the application of drugs in inhibiting the expression of proprotein convertase subtilisin / kexin type 9 (PCSK9) and / or enhancing the expression of low-density lipoprotein receptor (LDLR), which is of great significance for preventing and treating lipid metabolism disorders, liver diseases, and protecting the health of the cardiovascular system. The gastrodin in the embodiment of the present invention is an organic compound extracted from the dried root of the orchid plant Gastrodia elata, and the structural formula is as follows:

[0027]

[0028] Example 1

[0029] Western Blot technology was used to detect the effect of gastrodin on the expression of PCSK9 and LDLR proteins in Huh7 cells at the protein level.

[0030] After Huh7 cells were treated with gastrodin for 24 hours, total cell protein was extracted, and the protein concentration was determined using a BCA protein concentration assay kit. According to the results, PBS buffer was added to make the protein concentration uniform, and the protein was heated to denature. Then gel electrophoresis was performed, using a 10% gel and 124V electrophoresis for 70 minutes. The protein was then transferred to a nitrocellulose membrane and transferred at 100V for 100 minutes. After the transfer was completed, milk was used to block excess binding sites on the membrane. After that, it was incubated with the primary antibody and the secondary antibody successively. After incubation, the unbound antibody needed to be washed with a buffer to ensure that the antibody specifically bound to the target protein. Finally, the color developing solution was added, and the protein expression was analyzed using the principle of chemiluminescence. The protein expression of PCSK9 and LDLR was quantitatively analyzed using mage J software.

[0031] The results are as follows Figure 1 As shown, A shows the effect of different concentrations of gastrodin on the expression of PCSK9, LDLR and β-actin proteins, B and C show the results of quantitative analysis of PCSK9 and LDLR protein expression by Image J software, respectively. It can be seen that gastrodin inhibits the expression of PCSK9 in Huh7 cells at the protein level and enhances the expression of LDLR protein.

[0032] Example 2

[0033] qRT-PCR was used to detect the effect of gastrodin on the expression of PCSK9 and LDLR at the transcriptional level:

[0034] qRT-PCR was used to detect the expression of related genes, which specifically included three steps: RNA extraction, reverse transcription, and quantitative PCR amplification detection.

[0035] RNA extraction: After the administration of Huh7 cells in Example 1, the cell culture medium was completely removed and the cells were separated by 10 cm 2 Add 1ml TRI Reagent to the cells, shake and blow with a gun to completely lyse the cells, and then transfer the lysate to a centrifuge tube. Add 0.2ml chloroform to each sample, shake vigorously for 15 seconds, and place at room temperature for 2 to 3 minutes, then centrifuge at 12000g and 4℃ for 15 minutes, and draw the upper colorless aqueous phase to a new enzyme-free centrifuge tube. Add an equal volume of ice-cold isopropanol, mix well, and precipitate at room temperature for 10 minutes, then centrifuge at 12000g and 4℃ for 10 minutes to obtain RNA precipitation, and discard the supernatant. Wash the precipitate with 1ml 75% ethanol, centrifuge at 7500g and 4℃ for 5 minutes, discard the supernatant and dry the liquid, dissolve it with 30μL DEPC water after drying, and determine the concentration, and store it at -80℃.

[0036] Reverse transcription: When reverse transcribing RNA into cDNA, the extracted RNA needs to be thawed on ice and kept on ice at all times. The reaction solution is prepared on ice according to a specific system. The reverse transcription conditions are 25°C for 5 minutes, 50°C for 15 minutes, and 85°C for 5 minutes.

[0037] qRT-PCR detection: The PCR amplification program was 94°C denaturation for 15 seconds, 60°C annealing for 15 seconds, and 72°C extension for 25 seconds, for a total of 40 cycles, which was used to detect the expression of PCSK9 and other mRNAs. The relative quantitative method was used for calculation. The target gene primers were synthesized by Beijing Qingke Biotechnology.

[0038] The results are as follows Figure 2 As shown, A is the mRNA expression of PCSK9, and B is the mRNA expression of LDLR. It can be seen that gastrodin inhibits the mRNA expression of PCSK9 in Huh7 cells, and promotes the expression of LDLR mRNA, indicating that gastrodin affects the expression of PCSK9 and LDLR at the transcriptional level.

[0039] Example 3

[0040] Use ELISA kit (lot number: SEK10594) to detect PCSK9 secretion of Huh7 cells: Select ELISA kits with corresponding indicators and perform experimental detection according to the instructions: Antibody plating: Dilute capture antibody to working concentration with PBS and add 100μL to ELISA-specific 96-well plate. Seal the plate and incubate overnight on a shaker at 4°C. The next day, discard the capture antibody, add TBST, wash 3 times, and turn the special plate upside down on clean absorbent paper each time to remove residual TBST. Add 300μL of 2% BSA blocking buffer to each well and incubate at room temperature for 1h; after the end, add TBST and wash 3 times, turn the special plate upside down on clean absorbent paper to remove residual TBST. Take the Huh7 cell culture medium after administration, add 100μL of sample or standard solution to each well of the 96-well plate, seal the plate, and incubate at room temperature for 2h. Add TBST and wash 3 times. Remove the residual liquid for the next step. Add 100 μL of detection antibody to each well, seal the plate, incubate at room temperature for 1 hour, add TBST, and wash 3 times. Add 200 μL of substrate solution to each well, react at room temperature in the dark for 20 minutes. Add 50 μL of stop solution, gently tap the plate to mix the substrate thoroughly. Detect the absorbance value at a wavelength of 450 nm using an ELISA reader.

[0041] The results are as follows Figure 3As shown in Figure A, gastrodin inhibits the secretion of PCSK9 in Huh7 cells.

[0042] Dil-LDL fluorescence staining was used to investigate the effect of cells on LDL uptake capacity: Huh7 cells were seeded in a 12-well cell culture plate, and after the cells grew to 50% confluence, they were incubated with 20 μM gastrodin for 24 hours. The cell culture medium was discarded, and the cells were washed twice with PBS. The cells were then moved to serum-free culture medium and incubated with 20 μg / mL Dil-LDL in the dark at 37°C for 24 hours. After incubation, the cells were washed with PBS, fixed with 4% paraformaldehyde, and the cell nuclei were stained with DAPI. Finally, the cells were observed under a fluorescence microscope. The results are shown in Figure 2. Figure 3 As shown in B, it was found that after the use of gastrodin, the uptake of Dil-LDL by Huh7 cells was significantly increased, indicating that gastrodin can enhance the abundance and activity of LDLR on the cell surface.

[0043] Example 4

[0044] Establishment of relevant disease models: Male C57BL / 6J mice (6-8 weeks) were housed in the experimental animal center under SPF conditions of 22±2℃, light hours of 6:00-18:00, and relative humidity of (55±5)%. After one week of adaptive feeding, they were randomly divided into 7 groups, with 6 mice in each group: control group, model group, gastrodin group (i.e., Gas group, fed with 25, 50 and 100 mg / kg gastrodin, respectively), simvastatin group (i.e., Sim group, 3 mg / kg), and JAK2 agonist + gastrodin group (i.e., C-A1 group, 50 mg / kg gastrodin and 4 mg / kg C-A1). All groups were fed with a high-fat diet (HFD) for 12 weeks to establish the model. In the 8th week, the Gas group and Sim group were administered by gavage, while the C-A1 group was administered by intraperitoneal injection. All animal experiments were approved by the Animal Experiment Ethics Committee of Anhui University of Traditional Chinese Medicine.

[0045] After the experiment, the mice were euthanized, plasma was collected, the abdomen was opened to quickly collect the liver and other tissues, and the wet weight of the liver was weighed.

[0046] The results of liver analysis are as follows Figure 4 As shown, A is the statistical result of liver wet weight of each group of mice, and B is the liver index of each group of mice (liver index = liver weight / mouse body weight * 100). The results were subsequently analyzed, and the results showed that there was an obvious dose-dependent relationship between liver wet weight and gastrodin. However, it had little effect on the liver index of mice.

[0047] Example 5

[0048] By observing the triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) in the serum of mice, we explored the effect of gastrodin on lipid accumulation in related disease model animals. The specific process is as follows:

[0049] After the collected plasma was left at room temperature for 2 hours, it was centrifuged at 2000rpm for 15 minutes at room temperature, and the upper serum was transferred to a new 1.5mL centrifuge tube. 30μL of serum was added to 90μL PBS to dilute the serum 4 times. It was placed in the sample detection slot of the fully automatic biochemical analyzer to detect the content of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C).

[0050] The results are as follows Figure 5 As shown, A is the content of HDL-C in serum, B is the content of LDL-C in serum, C is the content of TC in serum, and D is the content of TG measured in serum. It can be seen that after treatment with gastrodin, the HDL-C content in serum increased significantly, and the levels of serum TC, LDL-C, and TG decreased significantly, indicating that gastrodin can improve lipid metabolism in the body.

[0051] Example 6

[0052] H&E staining and Oil Red O staining were used to observe the effect of gastrodin on lipid accumulation in the liver of related disease model animals. The specific process is as follows:

[0053] H&E staining: The liver tissue was fixed with 4% paraformaldehyde and then placed in an automatic tissue dehydrator for dehydration; embedded in a paraffin embedding machine, and slices with a thickness of about 5 μm were continuously cut on a paraffin slicer; then dewaxed with various concentrations of ethanol and xylene, the slices were immersed in an eosin dye tank for reaction, washed and then placed in a hematoxylin dye tank for reaction; after washing, dehydrated again in sequence, made transparent with xylene and sealed with a neutral resin; observed and collected images under a microscope.

[0054] Oil Red O staining to detect lipid accumulation in liver tissue: The liver lobe was separated from the whole liver, fixed with 4% paraformaldehyde for 24 hours, dehydrated with 30% sucrose solution, and then embedded with OCT freezing embedding agent. The tissue section was sliced ​​using a freezing microtome with a slice thickness of 10μm. The frozen sections were rewarmed and dried, fixed in the fixative for 15 minutes, washed with tap water, and dried; soaked in 60% isopropanol for 2 minutes; the sections were immersed in oil red stain for 30 minutes (covered and protected from light); the sections were taken out, stayed for 3 seconds, and then immersed in two cylinders of 60% isopropanol for differentiation, each for 3 seconds and 5 seconds. The sections were immersed in two cylinders of pure water for 10 seconds each; hematoxylin staining: the sections were taken out, stayed for 3 seconds, and then immersed in hematoxylin for 3-5 minutes, and then immersed in three cylinders of pure water for 5 seconds, 10 seconds, and 30 seconds each. The sections were bluing in the bluing solution for 3 minutes, and the sections were gently immersed in 2 cylinders of tap water for 5 seconds and 10 seconds respectively, and the staining effect was examined under a microscope; the sections were sealed with glycerol-gelatin sealing medium; and the images were observed and collected under a microscope.

[0055] The results are as follows Figure 6 As shown in the figure, morphological analysis shows that the liver tissue of mice in the normal group is bright red, while after being fed with a high-fat diet, the liver tissue gradually turns white and swells. After being treated with gastrodin, the color and state of the liver tissue gradually return to normal. H&E staining found that after administration, the structure of the liver lobule returned to normal, the arrangement of the hepatocyte cords became regular, and the number of vacuoles was significantly reduced. Oil Red O staining analysis showed that gastrodin significantly reduced the number of red lipid droplets.

[0056] Example 7

[0057] To explore the effect of gastrodin on reducing lipid accumulation in the liver of related disease model animals:

[0058] Detection of triglyceride (TG) and total cholesterol (TC) content in each group of mice in Example 4: Accurately weigh the liver tissue, add 9 times the volume of anhydrous ethanol at a ratio of weight (g): volume (mL) = 1:9, mechanically homogenize under ice water bath conditions, 2500 rpm, centrifuge for 10 minutes, and take the supernatant for testing. According to the instructions, add distilled water, calibration, sample and working solution respectively. Mix well, incubate at 37°C for 10 minutes, wavelength 500nm, and measure the absorbance value of each well with an enzyme marker. Calculate the TG and TC contents in the liver tissue according to the formula.

[0059] Determination of free fatty acid (FFA) content: Use physiological saline for liver tissue, use filter paper to absorb excess water from the tissue, weigh 0.1g tissue, add 1mL extract solution for ice bath homogenization, and centrifuge at 8000rpm, 4℃ for 10min. Dilute the standard with chloroform to 1, 0.8, 0.6, 0.4, 0.2, 0.1, 0.05μmol / mL according to the instructions. Add the reagents in the instructions in sequence. After fully shaking for 5min, let it stand for 15min, remove 0.2mL to a 96-well plate, and detect the absorbance at 550nm. Calculate the FFA content in liver tissue according to the formula.

[0060] The results are as follows Figure 7 As shown, A is the total cholesterol content in the liver, B is the triglyceride content measured in the liver, and C is the free fatty acid content measured in the liver. It can be seen that gastrodin significantly reduced the concentrations of TC, TG and FFA in the liver in a dose-dependent manner, indicating that gastrodin can improve lipid accumulation in mice induced by a high-fat diet.

[0061] Example 8

[0062] The liver tissue was ground with liquid nitrogen and weighed. Protease inhibitors were added to the lysis buffer in proportion to lyse the tissue. The tissue was centrifuged at 4°C, 12,000 r / min for 15 min. The supernatant was collected and protein expression was detected by Western Blot. Figure 8 As shown, compared with the model group, after treatment with gastrodin, the expression of PCSK9 was significantly weakened, while the expression of LDLR was enhanced.

[0063] Example 9

[0064] In the in vivo experiments of related disease model animals, the mechanism of action of gastrodin on PCSK9 and LDLR at the mRNA level was explored. The specific process is as follows:

[0065] Grind 100mg of mouse liver tissue, extract total RNA using 1mL RNA isolation reagent TRIzol, and homogenize thoroughly with a homogenizer or a microcentrifuge. Leave at room temperature for 5 minutes to fully lyse the sample. Add 0.2ml of chloroform to each sample, shake vigorously for 15s, and leave at room temperature for 2-3 minutes. Cool the centrifuge in advance, centrifuge at 12,000g, 4℃ for 15 minutes, and draw the upper colorless aqueous phase into a new enzyme-free centrifuge tube. Add an equal volume of ice-cold isopropanol to the supernatant, invert several times to mix, and precipitate at room temperature for 10 minutes. Centrifuge at 12,000g, 4℃ for 10 minutes, RNA precipitation can be seen at the bottom of the tube, and the supernatant is discarded. Add 1ml of 75% ethanol, invert to mix, centrifuge at 7,500g at 4℃ for 5 minutes, and discard the supernatant. Shake dry and carefully absorb all the liquid. After the RNA is dried, add 30uL of DEPC water to dissolve and store at -80℃. The remaining steps are consistent with the cell experiment (Example 2).

[0066] The results are as follows Fig. 9 As shown, A is the expression of PCSK9 protein, and B is the expression of LDLR protein. It can be seen that Gastrodin inhibits the mRNA of PCSK9 in mouse liver and promotes the expression of LDLR mRNA, which is consistent with the results of cell experiments.

[0067] Example 10

[0068] The serum PCSK9 concentration of mice was tested according to the PCSK9 Elisa kit according to the instructions (SEK50251), and the absorbance was detected at a wavelength of 450nm using an ELISA reader. Fig.10 As shown, it can be seen that gastrodin significantly reduced the secretion level of PCSK9 in the circulation.

[0069] Statistical analysis: The above data were analyzed using GraphPad Prism and Image J software, processed using SPSS22.0 statistical software, expressed as mean ± SD, and compared with the significance of differences between groups using post hoc test in ANOVA or T test. P < 0.05 was significant, and P < 0.01 was extremely significant.

[0070] The use of gastrodin in the preparation of drugs for inhibiting PCSK9 expression and / or enhancing LDLR expression, wherein the drugs are used to treat or prevent related diseases caused by abnormal PCSK9 expression and insufficient LDLR expression.

[0071] The related diseases include but are not limited to liver lipid metabolism disorders, liver damage, and vascular lesions in the cardiovascular system caused by abnormal lipid metabolism.

[0072] The drug inhibits PCSK9 expression and reduces its degradation effect on LDLR, thereby improving the transport and metabolism of lipids in the body and reducing the risk of abnormal lipid accumulation in the blood.

[0073] The drug enhances LDLR expression, improves the cell's ability to take up low-density lipoprotein, regulates lipid balance in the body, and alleviates body damage caused by lipid metabolism problems.

[0074] The drug inhibits PCSK9 expression and enhances LDLR expression at the same time, thereby synergistically improving lipid metabolism in the body, reducing the risk of cardiovascular disease, and alleviating liver damage caused by lipid overload.

[0075] The drug is a single active ingredient, gastrodin, or a combined drug composition comprising gastrodin and other drugs that can regulate lipid metabolism and protect cardiovascular or liver functions.

[0076] The other drugs are statins and other drugs that have the effects of regulating blood lipids and protecting cardiovascular system, such as simvastatin, atorvastatin or rosuvastatin.

[0077] The invention comprises a therapeutically effective amount of gastrodin and a pharmaceutically acceptable carrier.

[0078] The dosage forms include common pharmaceutical dosage forms such as oral preparations, injections or sustained-release preparations to meet the treatment needs of different patients.

[0079] The above description is only used to explain the preferred embodiments of the present invention, and is not intended to limit the present invention in any form. Therefore, any modifications or changes made to the present invention under the same inventive spirit should still be included in the scope of protection intended by the present invention.

Claims

1. Application of gastrodin in the preparation of drugs for regulating the expression of proprotein convertase subtilisin 9 and low-density lipoprotein receptor.

2. The application of gastrodin in the preparation of drugs for inhibiting the expression of proprotein convertase subtilisin 9.

3. Application of gastrodin in the preparation of drugs for enhancing the expression of low-density lipoprotein receptors.

4. A drug for inhibiting the expression of proprotein convertase subtilisin 9, characterized in that: Contains gastrodin.

5. The drug for inhibiting the expression of proprotein convertase subtilisin 9 according to claim 4, characterized in that: The medicine is a single active ingredient, namely gastrodin, or is a combination of gastrodin and excipients.

6. The drug for inhibiting the expression of proprotein convertase subtilisin 9 according to claim 5, characterized in that: The auxiliary material is simvastatin, atorvastatin or rosuvastatin.

7. A drug for enhancing the expression of low-density lipoprotein receptor, characterized in that: Contains gastrodin.

8. The drug for enhancing low-density lipoprotein receptor expression according to claim 7, characterized in that: The medicine is a single active ingredient, namely gastrodin, or is a combination of gastrodin and excipients.

9. The drug for enhancing low-density lipoprotein receptor expression according to claim 8, characterized in that: The auxiliary material is simvastatin, atorvastatin or rosuvastatin.

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