CN114569724B

CN114569724B - Application of ZFP36 gene in preparation of antihypertensive drug

Info

Publication number: CN114569724B
Application number: CN202210276837.3A
Authority: CN
Inventors: 张文程; 姜秀新; 崔秀茹
Original assignee: Shandong University
Current assignee: Qilu Hospital of Shandong University
Priority date: 2022-03-21
Filing date: 2022-03-21
Publication date: 2023-03-28
Anticipated expiration: 2042-03-21
Also published as: CN114569724A

Abstract

The invention relates to application of a ZFP36 gene in preparation of antihypertensive drugs. The invention discloses an important role of ZFP36 in regulating and controlling blood pressure stability by constructing a gene knockout mouse of a smooth muscle specificity knockout ZFP 36. Under physiological conditions, compared with a control mouse, the deletion of the ZFP36 gene of the ZFP36 knockout mouse leads to the reduction of intracellular calcium ions, causes the reduction of smooth muscle contraction, and further leads the blood pressure of the ZFP36 knockout mouse with the specificity of the smooth muscle to be obviously reduced. According to the invention, spontaneous hypertensive rat tail is used for injecting silent ZFP36 gene adeno-associated virus, and the silent ZFP36 gene is found to be capable of spontaneously hypertensive rat blood pressure. The invention takes ZFP36 gene as a target to prepare or screen antihypertensive drugs, and has important significance in hypertension treatment.

Description

Application of ZFP36 gene in preparation of antihypertensive drug

Technical Field

The invention relates to an application of a ZFP36 gene in preparation of antihypertensive drugs, belonging to the technical field of biological medicines.

Background

Hypertension is a clinical syndrome characterized by an increase in systemic arterial blood pressure (systolic and/or diastolic). In the case of no antihypertensive drug, the systolic pressure of 140mmHg or more and/or the diastolic pressure of 90mmHg or more, measured on three non-same days, can be defined as hypertension. Statistically, by 2014, there are over 10 billion patients with hypertension globally, and 27.9% of adults in china have hypertension. Hypertension is an important cause of death due to global diseases, causes damage to various organs such as heart, kidney, brain tissue and the like, approximately 9000 tens of thousands of people die from hypertension-related diseases every year, and is an important risk factor for cardiovascular diseases such as stroke and coronary heart disease. Hypertension induced by a definite cause such as renal, endocrine or aortic stenosis is called secondary hypertension, but 85% -90% of the hypertension has no definite cause and is called primary hypertension. Therefore, it is important to explore the mechanism of the occurrence of essential hypertension and to find an effective treatment scheme.

Endothelial cells, smooth muscle cells, and immune cells specifically accumulate in the vasculature, determining vascular tone and homeostasis. Among them, the vascular smooth muscle cells, as the main cells of the vascular wall, directly drive the contraction of the vascular wall by controlling the diameter of the blood vessel under the stimulation of biological stress and vasoactivity, thereby affecting the peripheral resistance and the blood pressure stability. There is evidence that abnormalities in the contractile state of vascular smooth muscle are sufficient to cause blood pressure disorders, thus elucidating the critical role of smooth muscle in regulating blood pressure.

Post-transcriptional regulation of genes, particularly mRNA stability, is an important step in regulating gene expression and can determine the final expression levels of mRNA and protein. Dysregulation of mRNA stability directly leads to abnormal expression of various genes including genes encoding growth factors, inflammatory cytokines, and proto-oncogenes, which underlies the pathogenesis of various diseases. The ZFP36 protein is an RNA-binding protein comprising a tandem Cys-His (CCCH) zinc finger domain and its primary role is to regulate target protein expression by reducing mRNA stability by binding to the AU element-rich region of the 3' untranslated region of the target gene mRNA. ZFP36 plays an important role in various cells such as macrophages, cardiac muscle cells, and tumor cells, but the role of ZFP36 in vascular smooth muscle is not known.

Conditional gene knockout refers to an experimental technique for knocking out a specific gene in a specific tissue cell or at a specific stage of cell development. The conditional gene knockout generally adopts a Cre/loxP recombination system, and Cre recombinase is site-specific recombinase and can mediate the specific recombination between two loxP sites, so that the gene sequence between the loxP sites is deleted or recombined. Conditional gene knock-out is of great importance for studying the function of a specific gene in a specific tissue cell and/or at a specific time, and for better establishing an animal model of human diseases.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides the application of the ZFP36 gene in the preparation of antihypertensive drugs. The invention clarifies the important function of ZFP36 in smooth muscle in regulating the blood pressure stability by constructing a mouse with vascular smooth muscle specificity knockout of ZFP36, and lays a foundation for the preparation of antihypertensive drugs.

The technical scheme of the invention is as follows:

the ZFP36 gene is applied to the preparation of antihypertensive drugs, and the nucleotide sequence of the ZFP36 gene is shown in SEQ ID No. 1.

According to the invention, the ZFP36 gene is preferably used for preparing antihypertensive drugs, and the ZFP36 gene comprises the following two aspects:

(1) The ZFP36 gene is used as an action target to be applied to the preparation of antihypertensive drugs;

(2) The ZFP36 gene is used as an action target to be applied to screening of antihypertensive drugs.

Preferably, the ZFP36 gene as an action target is applied to the preparation of antihypertensive drugs, and the preparation method comprises the following steps: the ZFP36 gene is used as an action target of a medicine or a preparation, the medicine or the preparation for resisting hypertension is prepared on the basis of interfering and inhibiting the ZFP36 gene, and the prepared medicine or the preparation can efficiently and specifically interfere and inhibit the transcription or translation of the smooth muscle cell ZFP36 gene, or can efficiently and specifically reduce the expression or activity of the smooth muscle cell ZFP36 protein, reduce the contractility of the smooth muscle cell and reduce the blood pressure.

Preferably, the ZFP36 gene as an action target is applied to screening antihypertensive drugs and is characterized in that: the ZFP36 gene is used as the action target of the medicine or the preparation, the antihypertensive medicine or the preparation is screened on the basis of interfering and inhibiting the ZFP36 gene, and the screened medicine or the preparation can efficiently and specifically interfere and inhibit the transcription or the translation of the smooth muscle cell ZFP36 gene, or can efficiently and specifically reduce the expression or the activity of the smooth muscle cell ZFP36 protein, reduce the contractility of the smooth muscle cell and reduce the blood pressure.

According to the present invention, the preparation or screening of the antihypertensive drug includes, but is not limited to: nucleic acid molecules, carbohydrates, lipids, small molecule chemicals, antibody drugs, polypeptides, proteins, or viruses.

Further preferably, when the antihypertensive drug is a nucleic acid molecule, the nucleic acid molecule includes, but is not limited to: antisense oligonucleotides, double-stranded RNA, small interfering RNA or short hairpin RNA. The nucleic acid molecule can interfere, inhibit or silence the ZFP36 gene, and reduce the expression or activity of ZFP36 protein in smooth muscle cells, thereby reducing hypertension.

Further preferably, when the antihypertensive drug is a virus, the virus contains a nucleotide sequence that interferes with expression of the ZFP36 gene. The virus can interfere, inhibit or silence the ZFP36 gene, and reduce the expression or activity of ZFP36 protein in smooth muscle cells, thereby reducing hypertension.

Preferably, according to the present invention, the antihypertensive drug further contains a pharmaceutically acceptable excipient; more preferably, the excipient is one or more of glucose, sucrose, sorbitol, mannose, starch, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, and water.

According to the invention, the antihypertensive drug is preferably a tablet, a pill, a powder or an injection.

The invention has the technical characteristics and beneficial effects that:

1. the invention constructs a smooth muscle specific ZFP36 knockout gene knockout mouse (ZFP 36) ^SMKO ) An important role for ZFP36 in the regulation of blood pressure stability is disclosed. Under physiological conditions, compared with a Control (CTR) mouse, the deletion of the ZFP36 gene of the ZFP36 knockout mouse leads to the reduction of intracellular calcium ions, causes the reduction of smooth muscle contraction, and further leads the blood pressure of the ZFP36 knockout mouse with the specificity of the smooth muscle to be obviously reduced.

2. In the AngII-induced pathological hypertension model, the knockout of the ZFP36 gene can effectively relieve hypertension, vascular remodeling and myocardial hypertrophy caused by angiotensin II (AngII). Meanwhile, the expression of the ZFP36 is interfered by injecting silent ZFP36 gene adeno-associated virus (AAV 9-ZFP36 shRNA) into tail vein of Spontaneous Hypertension Rats (SHR), and the silent ZFP36 gene is found to be capable of obviously reducing the blood pressure of the spontaneous hypertension rats. The invention takes ZFP36 gene as a target to prepare or screen antihypertensive drugs, and has important significance in hypertension treatment.

Drawings

Fig. 1 is a strategy flow diagram for conditional knock-out of the ZFP36 gene.

FIG. 2 shows the expression of ZFP36 gene in mouse smooth muscle;

in the figure, A is the expression condition of ZFP36 and alpha-SMA in mouse mesenteric artery smooth muscle detected by immunofluorescence, red fluorescence indicates alpha-SMA, green fluorescence indicates ZFP36, and a ruler is 20 mu m; b is the expression condition of ZFP36mRNA in aorta of the mouse detected by RT-PCR; CTR stands for control mouse，ZFP36 ^SMKO Represent smooth muscle-specific knockout ZFP36 mice.

FIG. 3 is a graph of blood pressure for mice of different ages;

in the figure, CTR represents a control mouse, ZFP36 ^SMKO Represents smooth muscle-specific knockout ZFP36 mice, sBP represents systolic blood pressure.

FIG. 4 is the effect of deletion of the ZFP36 gene on smooth muscle intracellular calcium;

in the figure, CTR represents the smooth muscle cells of control mice, ZFP36 ^SMKO Represents smooth muscle cells of a smooth muscle-specific knockout ZFP36 mouse, NE represents norepinephrine, ca ²⁺ Represents calcium ions.

FIG. 5 is a statistical plot of blood pressure two weeks after pumping of AngII in mice;

in the figure, A is a statistical graph of the systolic pressure of the mice; b is a statistical graph of mean arterial pressure of the mice; CTR + Saline represents the control rat pumping physiological Saline, CTR + AngII represents the control rat pumping AngII, ZFP36 ^SMKO + Saline represents smooth muscle specific knockout ZFP36 mice pumped in Saline, ZFP36 ^SMKO + AngII represents smooth muscle specific knockout ZFP36 mice pumping AngII, sBP being systolic pressure, MBP being mean arterial pressure.

FIG. 6 is a statistical graph of the thoracic aorta after pumping the mice into AngII for four weeks;

in the figure, A is a representative picture of HE staining of thoracic aorta of mice, and the scale is 100 μm; b is a histogram of the thickness of the tunica media of the thoracic aorta of the mouse; CTR + Saline represents the control rat pumping physiological Saline, CTR + AngII represents the control rat pumping AngII, ZFP36 ^SMKO + Saline represents a gene knock-out mouse pumped with normal Saline, ZFP36 ^SMKO + AngII stands for Gene knock-out mouse pumping into AngII.

FIG. 7 is a statistical plot of the change in heart after pumping of mice into AngII for four weeks;

in the figure, A is a representative picture of gross mouse heart and HE staining, and the scale is 1000 μm; b is a bar graph of mouse heart weight/body weight; CTR + Saline represents the control rat pumping physiological Saline, CTR + AngII represents the control rat pumping AngII, ZFP36 ^SMKO + Saline represents a gene knock-out mouse pumped with normal Saline, ZFP36 ^SMKO + AngII represents a groupPumping AngII into the knockout mouse;

FIG. 8 is the expression of ZFP36 protein in Spontaneously Hypertensive Rat (SHR) aortic smooth muscle cells following AAV9-ZFP36 shRNA injection;

in the figure, A is a western blot validation chart of ZFP36 protein in rat aortic smooth muscle cells; b is a statistical chart of the expression quantity of ZFP36 protein in rat aortic smooth muscle cells; SHR represents spontaneous hypertension rat, SHR + AAV9-CTR shRNA represents spontaneous hypertension rat tail vein injection control adeno-associated virus, SHR + AAV9-ZFP36 shRNA represents spontaneous hypertension rat tail vein injection ZFP36shRNA adeno-associated virus, GAPDH glyceraldehyde-3-phosphate dehydrogenase, and is protein internal reference;

FIG. 9 is a graph of blood pressure continuous variation after AAV9-ZFP36 shRNA virus tail vein injection of Spontaneous Hypertensive Rat (SHR);

in the figure, SHR represents spontaneous hypertensive rats, SHR + AAV9-CTR shRNA represents spontaneous hypertensive rat tail vein injection control adeno-associated virus, SHR + AAV9-ZFP36 shRNA represents spontaneous hypertensive rat tail vein injection ZFP36shRNA adeno-associated virus, and sBP is systolic pressure.

Detailed Description

The invention is further illustrated by the following examples, which are intended to be illustrative only and not to limit the scope of the invention.

ZFP36 ^flox/flox The mouse is available from Jacksonlab, USA, SM22-Cre mouse race Biotech, inc., and SHR rat Beijing Wintonia laboratory animal technology, inc.

The examples relate to drugs and reagents, which are all common commercial products unless otherwise specified; the experimental procedures referred to in the examples were carried out according to the routine procedures in the art unless otherwise specified.

Example 1 smooth muscle specific knockout of ZFP36 (ZFP 36) ^SMKO ) Mouse model construction

Will ZFP36 ^flox/flox The mice are mated with SM22-Cre mice which specifically express Cre recombinase in smooth muscle to obtain F1 generation ZFP36 ^flox/+ /SM22-Cre ⁺ Further crossing the mouse with F1 generation mouse to obtain the final productTo ZFP36 ^flox/flox /SM22-Cre ⁺ Mouse, littermate-born ZFP36 ^flox/flox /SM22-Cre ^- The mice were Control (CTR) mice. Will ZFP36 ^flox/flox /SM22-Cre ⁺ The sequence between the two loxP sites of the mouse is recombined, i.e., ZFP36 ^flox/flox /SM22-Cre ⁺ The ZFP36 gene in the mouse smooth muscle is silenced, the function of the ZFP36 gene is inhibited, thereby obtaining a mouse with smooth muscle specificity knockout of the ZFP36 gene, and the mouse uses the ZFP36 gene ^SMKO And (4) showing. A strategy flow diagram for a specific conditional knockout of the ZFP36 gene is shown in fig. 1.

The mesenteric artery is the main resistant vessel affecting blood pressure changes. The CTR and ZFP36 are combined ^SMKO The mesenteric artery of the mouse is taken out, the peripheral fat tissue is removed, and the mesenteric artery is embedded by OCT embedding medium to prepare a frozen section. The frozen sections were subjected to immunofluorescence staining, and as a result, ZFP36 was found as shown in FIG. 2A ^SMKO Most of the ZFP36 gene in the mesenteric artery of the mouse was removed and the ZFP36 protein could not be expressed.

The CTR and ZFP36 ^SMKO The aorta of the mouse is taken out, peripheral adipose tissues and the adventitia of the blood vessel are quickly stripped, and Trizol lysate is added to extract the tissue RNA. Verified by RT-PCR detection using ZFP36 primer, as shown in FIG. 2B, ZFP36 ^SMKO ZFP36mRNA expression was significantly reduced in mouse aortic smooth muscle. ZFP36 is described above ^SMKO The expression of the ZFP36 gene in the vascular smooth muscle of the mouse is obviously inhibited, thereby providing a good animal model for the subsequent research.

Example 2 role of smooth muscle ZFP36 Gene in blood pressure stabilization

Example 1 to test different month ages ZFP36 ^SMKO The blood pressure of the mice and the CTR mice is shown in FIG. 3.

As can be seen from FIG. 3, from 3 months of age, ZFP36 ^SMKO The systolic blood pressure of the mice is obviously reduced compared with the CTR mice, which shows that the ZFP36 gene plays an important role in regulating and controlling the blood pressure stability.

Calcium ions are a key signal for causing smooth muscle contraction. Extraction of CTR and ZFP36 ^SMKO Primary smooth muscle cells from mice, calcium ion (Ca) incubation ²⁺ ) Indicator Fluo-4 AM (commercially available from Kyoki Biotech) was stimulated with 1mM norepinephrine (NE, commercially available from Sigma), photographed by fluorescence microscopy (FIG. 4A), and the fluorescence intensity was calculated (FIG. 4B).

As can be seen from FIG. 4, the smooth muscle cell knockout of ZFP36 inhibits the vasoconstrictor NE-induced Ca ²⁺ And the increase shows that the deletion of the ZFP36 gene causes the reduction of intracellular calcium ions, and the reduction of smooth muscle contraction is caused, so that the blood pressure of a mouse with the smooth muscle specificity knockout ZFP36 is obviously reduced.

Example 3 smooth muscle knockout ZFP36 alleviates hypertension and vascular remodeling induced by AngII

12-week-old male ZFP36 obtained in example 1 ^SMKO Mice and CTR mice were given angiotensin II (AngII, 1000 ng/kg/min) by subcutaneous osmotic pump, with Saline (Saline) pumped as a control. Mice were divided into four groups: (1) CTR + Saline; (2) CTR + AngII; (3) ZFP36 ^SMKO +Saline；④ZFP36 ^SMKO +AngII。

1. Blood pressure was measured two weeks later in different groups of mice, and the results are shown in fig. 5. As seen from FIG. 5, ZFP36 was compared with the CTR group mice ^SMKO The systolic pressure and the mean arterial pressure of the mice are obviously reduced, which indicates that the knockout of the ZFP36 gene can effectively reduce the hypertension caused by AngII.

2. After pumping the mice into AngII for four weeks, the thoracic aorta of the mice was taken and paraffin sections were made, followed by HE staining, and the results are shown in fig. 6. As can be seen from FIG. 6, angII caused a significant increase in the intima-media thickness of the thoracic aorta of mice, but compared with the CTR group, ZFP36 was observed ^SMKO The increase in intima thickness in the thoracic aorta caused by AngII was significantly alleviated in the mice.

3. After pumping the mice into AngII for four weeks, the hearts of the mice were removed, photographed, paraffin sections were made of the hearts, and HE staining was performed as shown in fig. 7. From fig. 7, it can be seen that the increase in heart size and heart weight/body weight ratio caused by AngII is shown at ZFP36 ^SMKO Significant relief was obtained in mice.

Example 4 preparation of adeno-associated viruses interfering with ZFP36 Gene

1. Obtaining a target gene:

the ZFP36shRNA nucleic acid sequence is as follows: 5 'TAATCACTAGGTCGGATC-3';

5’-TATGTTCCAAAGTCCTCCG-3’；

5’-ATGAAGTGGCATCGAGAGC-3；

5’-AGCCTGAGAAGCTGATGCT-3’。

2. adeno-associated virus (AAV) recombinant vector construction and sequencing validation: the ZFP36shRNA nucleic acid sequence is subcloned into an AAV9 expression vector (sold by Shandong Wei Yan Bio Inc.) by means of enzyme digestion-ligation-transformation, and after positive cloning is obtained, the correctness of the insert fragment is confirmed by sequencing.

3. Packaging AAV9 virus: HEK293T cells with a degree of polymerization of 90% or more were plated according to a 1 ⁶ One). The medium was changed to serum-free medium 1 to 2 hours before plasmid transfer, and the desired gene plasmid and helper plasmid were transfected into HEK293T cells using a transfection reagent (Lipofectamine 3000). 24 hours after transfection, the medium was changed to new serum-free medium. And collecting the virus after 72 hours, blowing down the cells without discarding the culture medium, centrifuging to obtain a supernatant and a cell precipitate, precipitating the virus in the supernatant of the culture medium by using PEG8000, and collecting the virus precipitate after the precipitation is carried out overnight.

4. Virus purification and concentration: the virus mixture was purified by iodixanol density gradient centrifugation. The centrifuged virus liquid was concentrated in an ultrafiltration tube. Repeatedly blowing and beating the residual liquid in the ultrafiltration tube, sucking the liquid into a virus storage tube, adding virus storage liquid, and marking the name and the date.

5. And (3) virus titer detection: and (3) determining the number of virus particles by RT-PCR (reverse transcription-polymerase chain reaction), wherein the number of the virus particles (number/ml) = relative value to a standard substance, and obtaining the adeno-associated virus interfering the ZFP36 gene.

Example 5 interference with ZFP36 expression reduces blood pressure in Spontaneously Hypertensive Rats (SHR)

AAV9-ZFP36 shRNA was injected into 10-week-old male SHR via tail vein, and AAV9-CTR shRNA (available from Shandong Weizhen Bio Inc.) was injected as a control, i.e., SHR was divided into two groups: (1) SHR + AAV9-ZFP36 shRNA; (2) SHR + AAV9-CTR shRNA.

1. Rat tail tranquilizationThe quantity of adeno-associated virus by intravenous injection is 1X 10 ¹² vg/v, blood pressure changes were continuously monitored after tail vein injection of virus, as shown in fig. 9. As can be seen from FIG. 9, compared with the AAV9-CTR shRNA group injected, the SHR blood pressure is obviously reduced after AAV9-ZFP36 shRNA injected into the SHR tail vein interferes with ZFP36 expression.

2. The aorta of SHR is taken out, the protein lysate is added, the sample is ground to obtain tissue protein, 15 mu g of protein is taken for Western blot verification, and antibody of ZFP36 protein is used for detection, as shown in figure 8. As can be seen from FIG. 8, the expression level of ZFP36 protein in the aorta of rats injected with AAV9-ZFP36 shRNA is obviously reduced, and the interference efficiency of ZFP36 is verified.

The above results confirm the key role of ZFP36 gene in maintaining blood pressure: the ZFP36 not only has a regulation and control effect on blood pressure under physiological conditions, the silent ZFP36 can relieve AngII-induced pathological hypertension and vascular remodeling, but also can reduce the blood pressure of spontaneous hypertension rats by giving a method of injecting AAV9-ZFP36 shRNA into the tail vein of the spontaneous hypertension rats to interfere with the expression of the ZFP 36. In conclusion, the method is of great significance for finding out a medicine or a preparation capable of interfering the expression of the smooth muscle cell ZFP36 gene as an alternative medicine or preparation for resisting hypertension in the next step.

SEQUENCE LISTING

<110> Shandong university

Application of <120> ZFP36 gene in preparation of antihypertensive drug

<160> 1

<170> PatentIn version 3.5

<210> 1

<211> 960

<212> DNA

<213> hominis

<400> 1

atggatctct ctgccatcta cgagagcctc cagtcgatga gccatgacct gtcatccgac 60

cacggaggaa ccgaatccct cggaggactt tggaacataa actcggactc catcccgtct 120

ggggtcacct ctcgcctgac tggccgctcc actagcctgg tggagggccg aagctgtggc 180

tgggtacccc caccccctgg ttttgcacct ttggctcccc gcccaggccc tgagctgtca 240

ccctcaccta cttcgcctac tgcaactccc accacctcct ctcgatacaa gaccgagctc 300

tgtcggacct actcagaaag cgggcgttgt cgctacgggg ccaagtgcca gtttgctcac 360

ggcctgggtg aacttcgcca agccaatcgc caccccaagt acaaaacgga actctgccac 420

aagttctacc tccagggccg ctgcccctat ggctctcgat gccacttcat ccacaacccc 480

accgaggacc tagctctccc tggccagccc catgtgctgc gacaaagcat cagcttctcc 540

ggcttgccct caggccgcag aagctcgccg ccacctccag gcttttctgg cccttccctg 600

tcctcttgtt ccttttcgcc ttccagctcc ccaccgcccc ctggggatct tccactttcc 660

ccttctgcct tctctgctgc ccctgggacc cctgtgactc gaagagaccc taaccaggcc 720

tgttgcccct cctgccgaag gtctactacc cccagcacca tctgggggcc cttgggtggc 780

ctggctcgga gcccatctgc ccactctctg ggatccgatc ctgatgacta cgccagcagc 840

ggcagcagcc tgggggggtc agactcacct gtctttgagg caggggtgtt tgggcctccc 900

cagacccctg cacccccaag gcgtctcccc atcttcaatc gtatctctgt ctctgagtga 960

Claims

1. The ZFP36 gene is used as the application of a drug with an action target in the preparation of antihypertensive drugs, and the nucleotide sequence of the ZFP36 gene is shown as SEQ ID No. 1;

the drug using the ZFP36 gene as the action target is based on the interference inhibition ZFP36 gene, can efficiently and specifically interfere and inhibit the transcription or translation of the smooth muscle cell ZFP36 gene, or can efficiently and specifically reduce the expression of the smooth muscle cell ZFP36 protein.

2. The ZFP36 gene is used as an action target to be applied to screening antihypertensive drugs, and the nucleotide sequence of the ZFP36 gene is shown as SEQ ID No. 1;

the ZFP36 gene as an action target applied to screening of antihypertensive drugs refers to the following steps: the ZFP36 gene is used as the action target of the medicine, the antihypertensive medicine is screened on the basis of the interference inhibition ZFP36 gene, and the screened medicine can efficiently and specifically interfere and inhibit the transcription or translation of the smooth muscle cell ZFP36 gene or efficiently and specifically reduce the expression of the smooth muscle cell ZFP36 protein.

3. The use of claim 1 or 2, wherein the antihypertensive drug prepared or screened is: antisense oligonucleotides, double-stranded RNA, small interfering RNA or short hairpin RNA.

4. The use as claimed in claim 1 or claim 2 wherein the antihypertensive agent prepared or screened is a virus containing a nucleotide sequence that interferes with expression of the ZFP36 gene.

5. The use of claim 1 or 2, wherein the antihypertensive medicament further comprises a pharmaceutically acceptable excipient.

6. The use of claim 5, wherein the excipient is one or more of glucose, sucrose, sorbitol, mannose, starch, polyvinylpyrrolidone, cellulose, and water.

7. The use of claim 1 or 2, wherein the antihypertensive drug is a tablet, pill, powder or injection.