CN117265103A - Application of PiRd9, kit for diagnosing atherosclerosis and medicine for treating atherosclerosis - Google Patents
Application of PiRd9, kit for diagnosing atherosclerosis and medicine for treating atherosclerosis Download PDFInfo
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Abstract
The invention provides an application of PiRd9, a kit for diagnosing atherosclerosis and a medicament for treating atherosclerosis, and relates to the technical field of biomedical engineering, wherein the kit comprises small-molecule non-coding RNA PiRd9 related to atherosclerosis, the nucleotide sequence of the PiRd9 is shown as SEQ ID NO.1, and the expression of the PiRd9 is obviously reduced in an atherosclerosis sample; meanwhile, the over-expression of the piRd9 can obviously inhibit the expression of HAEC apoptosis and adhesion molecules induced by TNF-alpha, and the piRd9 regulates and controls the generation/development of atherosclerosis by influencing the expression of endothelial cell apoptosis and adhesion molecules, so as to achieve the purpose of treating atherosclerosis. Thus, piRd9 can be used as a biomarker for early diagnosis and treatment of atherosclerosis, and provides a new action target for diagnosis and treatment of atherosclerosis.
Description
Technical Field
The invention relates to the technical field of biomedical engineering, in particular to an application of PiRd9, a kit for diagnosing atherosclerosis and a medicament for treating atherosclerosis.
Background
Atherosclerosis has been identified as a major factor in cardiovascular events, being the major pathological change in coronary heart disease, peripheral vascular disease, cerebral infarction. Therefore, it is of great medical importance to study how to prevent and treat atherosclerosis.
Atherosclerosis is a complex process of atherosclerotic plaque formation involving a variety of mechanisms including inflammation and endothelial dysfunction. Endothelial cell dysfunction plays a critical role in the pathogenesis of many serious human diseases. There are also studies showing that endothelial dysfunction can persist during the development of atherosclerosis and can serve as an indicator of the risk of future cardiovascular events.
PiRNA is a novel small non-coding RNA that acts in a regulatory manner by binding to PIWI family proteins and is therefore termed PIWI-interacting RNAs (PIRNAs). piRNAs can bind to PIWI proteins to form piRNA/PIWI complexes, thereby affecting multiple physiological and pathological processes such as transposon silencing, epigenetic regulation, spermatogenesis, germ stem cell maintenance, genomic rearrangement, and protein regulation. Although it is generally believed that piRNAs play an important role in germ cell development, recent evidence suggests that piRNAs play a critical role in the formation of various diseases such as tumors, and that their expression is also significantly altered in some common heart diseases in clinic, such as myocardial infarction and myocardial hypertrophy. The biological function of piRNA in cardiovascular disease, cardiac physiology and pathogenesis of various diseases is not known so far and is still in continuous research and study stage.
In view of this, the present invention has been made.
Disclosure of Invention
One of the purposes of the present invention is to provide the application of piRd9 as a biomarker in the preparation of products for diagnosing atherosclerosis, so as to achieve effective diagnosis of atherosclerosis, and at least solve one of the technical problems existing in the prior art.
The second object of the invention is to provide a use of a substance overexpressing piRd9in the preparation of a product for the treatment of atherosclerosis, in order to achieve targeted treatment of atherosclerosis, at least solving one of the technical problems existing in the prior art.
In order to achieve the above object of the present invention, the following technical solutions are specifically adopted:
in a first aspect, the invention provides the use of piRd9 as a biomarker in the manufacture of a product for diagnosing atherosclerosis, the nucleotide sequence of piRd9 being as shown in SEQ ID No. 1.
Further, the product comprises a reagent or a kit.
Further, the atherosclerosis includes one or more of aortic atherosclerosis, coronary atherosclerosis, cerebral arteriosclerosis, renal atherosclerosis, mesenteric atherosclerosis and lower limb atherosclerosis.
In a second aspect, the invention also provides an application of a substance over-expressing piRd9in preparing a product for treating atherosclerosis, wherein the nucleotide sequence of piRd9 is shown as SEQ ID NO. 1.
Further, the product includes a medicament.
In a third aspect, the invention also provides a reagent or kit for diagnosing atherosclerosis, the reagent or kit comprises a primer for recognizing piRd9, and the nucleotide sequence of piRd9 is shown as SEQ ID NO. 1.
Further, the nucleotide sequences of the primers are shown as SEQ ID NO.2 and SEQ ID NO. 3.
In a fourth aspect, the present invention also provides a medicament for treating atherosclerosis, the medicament comprising a substance that overexpresses piRd9, the nucleotide sequence of piRd9 being shown in SEQ ID No. 1;
further, the piRd9 overexpressing substance includes at least one of the following i) -iv):
Ⅰ)piRd9；
II) recombinant vector containing coding gene of piRd 9;
III) recombinant viruses containing the coding gene of piRd 9;
IV) a recombinant viral vector containing the coding gene of piRd 9;
preferably, the medicament further comprises a pharmaceutically acceptable carrier;
further, the dosage form of the drug includes injection preparations including subcutaneous injection preparations and intravenous injection preparations or oral preparations.
The present invention provides an atherosclerosis-related piRNA: piRd9, piRd9 is an atherosclerosis-related piRNA, expression is significantly down-regulated in an atherosclerosis sample, and the aim of effectively diagnosing atherosclerosis can be achieved by specifically recognizing piRd 9; meanwhile, the over-expression of the piRd9 can obviously inhibit the expression of HAEC apoptosis and adhesion molecules induced by TNF-alpha, and the piRd9 regulates and controls the generation/development of atherosclerosis by influencing the expression of endothelial cell apoptosis and adhesion molecules, so as to achieve the purpose of treating atherosclerosis. Therefore, the piRd9 can be used as a biomarker for early diagnosis and treatment of atherosclerosis, provides a new action target for diagnosis and treatment of atherosclerosis, detects the expression level of the piRd9, and has potential value for prognosis evaluation of atherosclerosis. The application principle is scientific and reliable, different products such as a piRd9 detection kit or a medicine taking piRd9 as a target point can be developed to diagnose and/or treat atherosclerosis, and the kit is simple and convenient to use and operate, good in safety and environment-friendly in application.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 shows the results of the test of the expression level of piRd9in an animal atherosclerosis model experiment provided in example 1 of the present invention;
FIG. 2 shows the results of the measurement of the level of piRd9 expression in an atherosclerotic patient according to example 2 of the present invention;
FIG. 3 shows the results of the in vitro atherosclerosis cell model test provided in example 3 of the present invention for the level of piRd9 expression;
FIG. 4 shows the results of experiments in which piRd9 provided in example 4 inhibited the expression of endothelial cell apoptosis-related proteins;
FIG. 5 shows the experimental results of apoptosis detection when piRd9 is overexpressed provided in example 4 of the present invention;
FIG. 6 shows the results of an experiment for inhibiting the expression of endothelial cell adhesion molecules by piRd9 provided in example 4 of the present invention;
FIG. 7 shows the results of experiments for inhibiting the expression of endothelial apoptosis-related proteins in the presence of piRd9 according to example 4 of the present invention;
FIG. 8 shows the results of apoptosis assays for inhibiting piRd9 expression provided in example 4 of the present invention;
FIG. 9 is a graph showing the results of an experiment for inhibiting the expression of endothelial cell adhesion molecules when piRd9 is expressed in accordance with example 4 of the present invention;
FIG. 10 is a graph showing the observed statistics of intravenous piRd9 atherosclerotic plaques in a mouse atherosclerosis model provided in example 5 of the present invention.
Detailed Description
Unless defined otherwise herein, scientific and technical terms used in connection with the present invention shall have the meanings commonly understood by one of ordinary skill in the art. The meaning and scope of terms should be clear, however, in the event of any potential ambiguity, the definitions provided herein take precedence over any dictionary or extraneous definition. In this application, the use of "or" means "and/or" unless stated otherwise. Furthermore, the use of the term "include" and other forms is not limiting.
Generally, the nomenclature used in connection with the cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization described herein and the techniques thereof are those well known and commonly employed in the art. Unless otherwise indicated, the methods and techniques of the present invention are generally well known in the art and are performed according to conventional methods as described in various general and more specific references cited and discussed throughout the present specification. Enzymatic reactions and purification techniques are performed according to manufacturer's instructions, as commonly accomplished in the art, or as described herein. Nomenclature used in connection with the analytical chemistry, synthetic organic chemistry, and medical and pharmaceutical chemistry described herein, and the laboratory procedures and techniques therefor, are those well known and commonly employed in the art.
In one aspect, the invention provides the use of piRd9 as a biomarker in the manufacture of a product for diagnosing atherosclerosis, the nucleotide sequence of piRd9 being as shown in SEQ ID NO. 1.
Experiments of the inventor of the invention show that the expression of piRd9 is significantly reduced in an atherosclerosis mouse model and a TNF-alpha induced HAEC in vitro atherosclerosis model, and the aim of effectively diagnosing atherosclerosis can be achieved by specifically detecting piRd 9.
In the present invention, piRd9 contains a nucleotide sequence shown as SEQ ID NO.1, and it is meant that piRd9 may contain other functional sequences such as a tag sequence or a linker sequence in addition to the nucleotide sequence shown as SEQ ID NO. 1.
In some preferred embodiments, the product comprises a reagent or kit.
In some preferred embodiments, the atherosclerosis comprises one or more of aortic atherosclerosis, coronary atherosclerosis, cerebral arteriosclerosis, renal atherosclerosis, mesenteric atherosclerosis and lower limb atherosclerosis.
The invention also provides application of a substance for over-expressing piRd9in preparation of products for treating atherosclerosis, and the nucleotide sequence of the piRd9 is shown as SEQ ID NO. 1.
In some preferred embodiments, the product comprises a medicament.
The over-expression of the piRd9 can obviously inhibit the expression of HAEC apoptosis and adhesion molecules induced by TNF-alpha, and the piRd9 controls and inhibits the generation and development of atherosclerosis by influencing the expression of endothelial cell apoptosis and adhesion molecules, thereby achieving the purpose of treating atherosclerosis.
The invention also provides a reagent or a kit for diagnosing atherosclerosis, which comprises a primer for identifying piRd9, wherein the nucleotide sequence of piRd9 is shown as SEQ ID NO. 1.
In some preferred embodiments, the nucleotide sequence of the primer is shown as SEQ ID NO.2 and SEQ ID NO. 3.
The invention also provides a medicine for treating atherosclerosis, which comprises a substance for over-expressing piRd9, wherein the nucleotide sequence of piRd9 is shown as SEQ ID NO. 1;
in some preferred embodiments, the piRd9 overexpressing agent comprises at least one of i) -iv) as follows:
Ⅰ)piRd9；
II) recombinant vector containing coding gene of piRd 9;
III) recombinant viruses containing the coding gene of piRd 9;
IV) a recombinant viral vector containing the coding gene of piRd 9;
preferably, the medicament further comprises a pharmaceutically acceptable carrier;
in some preferred embodiments, the dosage form of the medicament comprises an injectable formulation or an oral formulation, the injectable formulation comprising a subcutaneous injection formulation and an intravenous injection formulation.
The piRd9 can provide a new action target for diagnosis and treatment of atherosclerosis, and simultaneously detect the expression level of the piRd9, has potential value for prognosis evaluation of atherosclerosis, has scientific and reliable application principle, can develop different products, such as a piRd9 detection kit or a medicament taking the piRd9 as a target, and is used for diagnosing and/or treating atherosclerosis, and has the advantages of simple and convenient use and operation, good safety and environment-friendly application.
Diagnosis and/or treatment of atherosclerosis means that the expression of piRd9 provided by the present invention can be used for diagnosing atherosclerosis, or for treating atherosclerosis, or for both diagnosing atherosclerosis and treating atherosclerosis.
The medicament for treating atherosclerosis provided by the invention can comprise one or two or more of piRd9, a recombinant vector containing a coding gene of piRd9 or a recombinant viral vector containing a coding gene of piRd 9.
The carrier can effectively wrap one or two or more of piRd9, a recombinant vector containing a coding gene of the piRd9 or a recombinant viral vector containing a coding gene of the piRd9, and is carried into the body to be released, so that the effect of drug administration and treatment is achieved.
Injectable formulations include formulations which may be prepared in any injectable acceptable form, for example, but not limited to, injectable solutions or powders. Injection means include, but are not limited to, subcutaneous or intravenous injection; oral formulations include, but are not limited to, capsules or tablets.
The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The main reagents and instrument information used in the embodiments of the present invention are as follows:
the terms involved in the following examples and drawings are explained as follows:
AS: atherosclerosis.
APOE -/- : knocking out the apolipoprotein E.
HAEC: human aortic endothelial cells.
NC: negative control.
Nc+tnf- α: TNF- α treated negative control group.
piRd9 mic: the piRd 9-overexpressing cell experimental group.
piRd9 mic+tnf- α: TNF- α treatment was performed on the cells of the piRd 9-overexpressing experimental group.
piRd9 inhibitor: experimental groups for inhibiting piRd9 expression.
piRd9 inhibitor+tnf- α: TNF-alpha treatment inhibited piRd9 expression in the experimental group.
Example 1 variation of piRd9 expression levels in animal atherosclerosis model experiments
In this example, a control group (group C57) was a normal diet C57 mice, and a high fat diet APOE was used -/- Mice were modeled for atherosclerosis as an experimental group (APOE -/- A group).
Wherein, the number of mice in each group is 8, and the mice are all 8-week-old male mice.
Extraction of C57 group and APOE respectively by Trizol method -/- Total aortic RNAs of the group; real-time fluorescent quantitative PCR is carried out, specifically: the reverse transcription kit is used for reversing RNA into cDNA by adopting a stem-loop method, and the reverse transcription amplification conditions are as follows: 37 ℃ for 15min;85 ℃,5s; preserving at 4 ℃. Quantitative detection of cDNA obtained after reverse transcription is carried out by using a Real-Time PCR instrument, a qRT-PCR system is shown in a table 1, and simultaneously U6 is selected as an internal reference, and amplification conditions are as follows: 95 ℃ for 30s;95 ℃,10s,60 ℃,30s, followed by 40 cycles. Wherein the piRd9 forward primer is: 5'GGGTGTAAACATCCCCGACTG 3' (SEQ ID NO. 2); the universal reverse primer is: 5'GTGCAGGGTCCGAGGT 3' (SEQ ID NO. 3). The U6 reverse primer was 5'TGGTGTCGTGGAGTCG 3' (SEQ ID NO. 4) and the U6 forward primer was 5'CTCGCTTCGGCAGCACA 3' (SEQ ID NO. 5).
TABLE 1qRT-PCR System
The expression level of piRd9 was detected by real-time fluorescent quantitative PCR technique, the results are shown in FIG. 1, and the results show that APOE was compared with C57 group -/- The level of piRd9 expression was significantly reduced in the group (< P < 0.01), indicating that piRd9 expression was significantly reduced in the atherosclerosis mouse model.
In the present example, the fat-rich feed was different from the normal feed in that the fat content of the fat-rich feed was 20%, the cholesterol content was 1.25%, and the balance was the normal diet. The normal diet included 4.3% fat, cholesterol free.
Example 2 variation of piRd9 expression levels in atherosclerotic patients
The healthy subjects of this example were used AS a control group and an atherosclerotic subject was used AS an experimental group (AS subject group), wherein the atherosclerotic subject had a coronary angiography result stenosis degree of > 70% and had severe inflammation, tumor and type 2 diabetes. Wherein 25 persons in each group are aged 40-80 years.
Serum total RNA was extracted from the control group and AS patient group, respectively, by the trizol method.
The expression level of piRd9in serum total RNA was measured by the real-time fluorescent quantitative PCR method of example 1, and the specific results are shown in fig. 2, which show that the expression level of piRd9in AS patient group was significantly reduced (P < 0.0001) relative to control group, and that piRd9 expression was significantly reduced in atherosclerosis patients.
Example 3 changes in the expression level of piRd9in an in vitro model of atherosclerosis cells
In this example, an in vitro model experiment of atherosclerosis cells was established using TNF- α to treat HAEC. The method comprises the following steps: HAEC24 h were treated with TNF- α at concentrations of 10ng/ml, 20ng/ml and 40ng/ml, respectively, and a control group was set, with TNF- α at a concentration of 0ng/ml, total RNA was extracted by the trizol method, and the level of piRd9 expression was detected by the real-time fluorescent quantitative PCR method of example 1.
Specific results are shown in FIG. 3, in which the levels of piRd9 expression were significantly down-regulated in treatments at concentrations of 10ng/ml, 20ng/ml and 40ng/ml, with the most significant down-regulation at concentrations of 20ng/ml, relative to treatments at concentrations of TNF- α of 0 ng/ml. It was shown that overexpression of piRd9 significantly inhibited TNF- α -induced HAEC apoptosis and expression of adhesion molecules.
Example 4 experiments of piRd9 inhibiting endothelial apoptosis and expression of adhesion molecules
In this example, HAEC was used as a subject for transfection of piRd9 over-expressed pharmaceutical compositions. The preparation method of the HAEC transfected piRd9 over-expression pharmaceutical composition is as follows (6-well plate):
(1) 5 μl Lipofectamine 3000+125 μl serum-free high sugar F-12K culture medium;
(2) Solution B, 5. Mu.l of piRd9 mic/5. Mu. l negative control +125. Mu.l of serum-free high sugar F-12K medium, mix well and stand for 3min; wherein piRd9 mic is the RNA sequence of piRd9, specifically 5'-UGUAAACAUCCCCGACUGGAAGCG-3' (SEQ ID No. 6).
(3) Slowly adding the solution A into the solution B, gently mixing, and standing the mixed solution for 10-15min;
(4) The mixed reagent was added dropwise to 1740. Mu.l of cells in F-12K medium containing 10% FBS, and the mixture was homogenized and cultured continuously.
24 hours after transfection, the piRd9 overexpressing pharmaceutical composition was transfected with HAEC for 24 hours using TNF-a induction treatment.
Meanwhile, a negative control is arranged, and in the negative control, the piRd9 mic in the preparation method of the piRd9 over-expression pharmaceutical composition is replaced by a piRd9 random sequence, and the piRd9 random sequence is 5'-UUCUCCGAACGUGUCACGUTT-3' (SEQ ID NO. 7).
HAEC apoptosis-related molecules (PARP, active-Caspase3, bax/Bcl 2) were detected by WB assay, and as shown in FIG. 4, the expression of apoptosis-related molecules in piRd9 mimic group was significantly reduced relative to NC group, and that in piRd9 mimic+TNF- α group relative to NC+TNF- α group; meanwhile, an Annexin V-FITC/PI kit is adopted to detect the apoptosis condition of HAEC, and the result is shown in figure 5, wherein the fluorescence expression level of the piRd9 mimic group is obviously reduced relative to the NC group, and the apoptosis-related molecule expression of the piRd9 mimic+TNF-alpha group is obviously reduced relative to the NC+TNF-alpha group. It is known that piRd9 overexpression can inhibit expression of apoptosis-related molecules caused by TNF- α, reducing apoptosis. The expression of adhesion molecules (ICAM-1 and VCAM-1) is detected by WB experiments, and the specific results are shown in FIG. 6, wherein the expression of ICAM-1 and VCAM-1 in the piRd9 mic group is obviously reduced relative to the NC group; relative to NC+TNF- α group, expression of ICAM-1 and VCAM-1 in piRd9 mic+TNF- α group was significantly reduced; it is known that overexpression of piRd9 inhibits TNF- α induced expression of adhesion molecules.
To further illustrate the relationship between piRd9 and endothelial cell apoptosis and adhesion molecule expression, experiments were set up to inhibit endothelial cell expression of piRd 9.
The pharmaceutical compositions for inhibiting piRd9 expression were transfected using HAEC as a subject in experiments for inhibiting endothelial cell expression piRd 9. The preparation method of the HAEC transfection inhibition piRd9 expression pharmaceutical composition is as follows (6-well plate):
(1) 5 μl Lipofectamine 3000+125 μl serum-free high sugar F-12K culture medium;
(2) Solution B, 5. Mu.l of piRd9 inhibitor/5. Mu. l negative control +125. Mu.l of serum-free high sugar F-12K medium, mix well and stand for 3min; wherein the piRd9inhibitor sequence is 5'-CGCUUCCAGUCGGGGAUGUUUACA-3' (SEQ ID NO. 8).
(3) Slowly adding the solution A into the solution B, gently mixing, and standing the mixed solution for 10-15min;
(4) The mixed reagent was added dropwise to 1740. Mu.l of cells in F-12K medium containing 10% FBS, and the mixture was homogenized and cultured continuously.
24 hours after transfection, the piRd9 overexpressing pharmaceutical composition was transfected with HAEC for 24 hours using TNF-a induction treatment.
Meanwhile, a negative control is set, and the piRd9inhibitor in the preparation method of the piRd9 over-expression pharmaceutical composition is replaced by a random sequence, specifically 5'-CAGUACUUUUGUGUAGUACAA-3' (SEQ ID NO. 9).
HAEC apoptosis-related molecules (PARP, active-Caspase3, bax/Bcl 2) are detected by WB experiment, and the result is shown in figure 7, and compared with NC group, the expression of apoptosis-related molecules of piRd9inhibitor group is obviously increased; compared with the NC+TNF-alpha group, the expression of ICAM-1 and VCAM-1 in the piRd9 inhibitor+TNF-alpha group is obviously increased; meanwhile, an Annexin V-FITC/PI kit is adopted to detect the apoptosis condition of HAEC, and the result is shown in figure 8, and compared with an NC group, the fluorescence expression level of a piRd9inhibitor group is obviously increased; the level of fluorescence expression was significantly increased in the piRd9inhibitor + TNF- α group relative to the NC + TNF- α group. It is known that inhibition of piRd9 expression promotes expression of apoptosis-related molecules caused by TNF- α, promoting apoptosis. The expression of adhesion molecules (ICAM-1 and VCAM-1) is detected by a WB experiment, and the specific results are shown in FIG. 9, and compared with the NC group, the expression of ICAM-1 and VCAM-1 in the piRd9inhibitor group is obviously increased; compared with the NC+TNF-alpha group, the expression of ICAM-1 and VCAM-1 in the piRd9 inhibitor+TNF-alpha group is obviously increased; it is known that the deletion of piRd9 expression promotes TNF- α induced expression of adhesion molecules.
Therefore, through over-expression of piRd9, endothelial cell apoptosis and adhesion molecule expression can be inhibited to regulate and control the generation and development of atherosclerosis, thereby achieving the purpose of treating atherosclerosis.
Example 5 inhibition of atherosclerosis by intravenous injection of piRd9in an atherosclerosis model animal experiment
This example detects the effect of piRd9 on atherosclerosis by intravenous injection of piRd9 into the tail of a mouse. APOE is first fed on a high fat diet -/- Mice were modeled for 20 weeks and then divided into three groups and piRd9-agomir (0.8 mg/kg) of APOE was injected -/- The mice are APOE -/- +pirna group, APOE injected with DEPC water -/- The mice are APOE -/- +depc group, while normal diet fed C57 mice were used as controls, injected 2 times per week for 4 weeks. Finally, the lesion plaque area formation condition is observed through the dissected aortic oil red staining of the mice. Specific results are shown in FIG. 10, relative to APOE -/- +DEPC group, APOE -/- The +pirna group lesions showed a significant decrease in plaque area, demonstrating that piRd9 is able to inhibit AS progression, demonstrating that piRd9 plays an important role in atherosclerosis progression.
PiRd9 is a piRNA related to the occurrence and development of atherosclerosis, can inhibit the occurrence and development of atherosclerosis, and has potential value in diagnosis and/or prognosis evaluation of atherosclerosis by detecting the expression level of the PiRd9in peripheral blood plasma; through piRd9 overexpression, has potential value in preventing and/or treating atherosclerosis.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (10)
- Use of piRd9 as biomarker for the preparation of a product for diagnosing atherosclerosis, the nucleotide sequence of piRd9 being shown in SEQ ID No. 1.
- 2. The use according to claim 1, wherein the product comprises a reagent or a kit.
- 3. The use according to claim 2, wherein the atherosclerosis comprises one or more of aortic atherosclerosis, coronary atherosclerosis, cerebral arteriosclerosis, renal atherosclerosis, mesenteric atherosclerosis and lower limb atherosclerosis.
- 4. Use of a substance overexpressing piRd9in the preparation of a product for the treatment of atherosclerosis, said piRd9 having the nucleotide sequence shown in SEQ ID No. 1.
- 5. The use according to claim 4, wherein the product comprises a medicament.
- 6. A reagent or kit for diagnosing atherosclerosis, wherein the reagent or kit comprises a primer for recognizing piRd9, and the nucleotide sequence of piRd9 is shown as SEQ ID No. 1.
- 7. The reagent or kit according to claim 6, wherein the nucleotide sequence of the primer is shown in SEQ ID NO.2 and SEQ ID NO. 3.
- 8. A medicament for treating atherosclerosis, which comprises a substance for over-expressing piRd9, wherein the nucleotide sequence of piRd9 is shown as SEQ ID No. 1.
- 9. The medicament of claim 8, wherein the substance that overexpresses piRd9 comprises at least one of the following i) -iv):Ⅰ)piRd9；II) recombinant vector containing coding gene of piRd 9;III) recombinant viruses containing the coding gene of piRd 9;IV) a recombinant viral vector containing the coding gene of piRd 9;preferably, the medicament further comprises a pharmaceutically acceptable carrier.
- 10. The medicament according to claim 8 or 9, wherein the dosage form of the medicament comprises an injectable formulation or an oral formulation, the injectable formulation comprising a subcutaneous injection formulation and an intravenous injection formulation.
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