CN109055544A - Atherosclerosis molecular marker and its application - Google Patents
Atherosclerosis molecular marker and its application Download PDFInfo
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- CN109055544A CN109055544A CN201811140906.8A CN201811140906A CN109055544A CN 109055544 A CN109055544 A CN 109055544A CN 201811140906 A CN201811140906 A CN 201811140906A CN 109055544 A CN109055544 A CN 109055544A
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Abstract
The present invention relates to a kind of atherosclerosis molecular marker and its applications.The atherosclerosis molecular marker can preferably reflect the development situation of atherosclerosis, to be applied to the Related product of preparation diagnosis or detection atherosclerosis, enrich the diagnosis and detection means of atherosclerosis.And the atherosclerosis molecular marker is able to suppress the adhesive attraction between monocyte THP-1 and vascular endothelial cell HUVECs, and inhibit the expression of the inflammatory factors such as adhesion factor and chemotactic factor (CF), to be effectively suppressed the overactivity of blood vessel endothelium inflammation, therefore it is also used as inhibiting the molecular drug target spot of formation and the development of atherosclerosis, for the pathogenesis of further studying atherosclerotic, explores its protective agents and new empirical theory basis and direction are provided.
Description
Technical field
The present invention relates to field of atherosclerosis, more particularly to a kind of atherosclerosis molecular marker and its answer
With.
Background technique
Atherosclerosis is a kind of chronic inflammatory diseases, it mainly occurs since low-density lipoprotein (LDL) is metabolized
Disorder, the inner membrance deposition of hypodermic layer is caused in the blood vessels.Clinically, atherosclerosis and myocardial infarction, apoplexy, lack
These common cardiovascular diseases such as hemorrhagic heart pain and hypertension suffer from close relationship.Currently, by artery
The cardiovascular and cerebrovascular disease that atherosis is caused, which has become, endangers one of principal disease of human health.According to the World Health Organization
The latest data of WHO counts display, and it is dead that the number for dying of cardiovascular and cerebrovascular disease, which accounts for the 48% of all uninfection total numbers of persons,
In twice or more of cancer occurrence numbers.Therefore, the pathogenesis of further studying atherosclerotic, artery congee can be used as by seeking
The important symbol object of sample hardening clinical diagnosis has a very important significance.
Summary of the invention
Based on this, it is necessary to which providing one kind can be as the Atherosclerosis of the marker of atherosclerosis clinical diagnosis
Chemoattractant molecule marker.
A kind of atherosclerosis molecular marker, the atherosclerosis molecular marker are long-chain non-coding RNA,
It has the nucleotide sequence as shown in SEQ ID NO.1.
The present invention also provides a kind of PCR amplification primers, including are used for the above-mentioned Atherosclerosis chemoattractant molecule of specific amplification
The upstream primer and downstream primer of marker.
The upstream primer has the nucleotide sequence as shown in SEQ ID NO.2 in one of the embodiments, described
Downstream primer has the nucleotide sequence as shown in SEQ ID NO.3.
The present invention also provides a kind of siRNA, sense strand and antisense strand including complementation, and the siRNA
The expression of above-mentioned atherosclerosis molecular marker can specifically be inhibited.
The sense strand has the nucleotide sequence as shown in SEQ ID NO.2 in one of the embodiments, described anti-
Adopted chain has the nucleotide sequence as shown in SEQ ID NO.3.
The present invention also provides above-mentioned atherosclerosis molecular marker, above-mentioned PCR amplification primer or above-mentioned small interference
Application of the RNA in the product of preparation diagnosis or detection atherosclerosis.
The product is detection reagent, kit, genetic chip or Test paper in one of the embodiments,.
The present invention also provides above-mentioned atherosclerosis molecular marker, above-mentioned PCR amplification primer or above-mentioned small interference
RNA is preparing the application in the drug for preventing or treating atherosclerosis.
The present invention also provides a kind of for detecting the kit of atherosclerosis, including above-mentioned PCR amplification primer.
It in one of the embodiments, further include that RNA is extracted in reagent, reverse transcription reagents and PCR amplification reagent at least
It is a kind of.
2/3rds sequence is by reverse transcription in the gene order of more than 30 hundred million base-pairs of the mankind, and finally only less than
2% nucleic acid sequence is for encoding albumen, and most gene does not express protein, this genoid is referred to as non-coding RNA.It is non-
Coding RNA includes short chain non-coding RNA and long-chain non-coding RNA, they may participate in cell differentiation and a on many levels
Body developmental regulation, it is closely related with various diseases.Present inventor has found under study for action, long-chain non-coding RNA NKILA
The expression quantity of (sequence is as shown in SEQ ID NO.1) in the peripheral blood mononuclear cells of Atheromatosis people is significantly lower than just
Expression quantity (P value < 0.05) in the peripheral blood mononuclear cells of ordinary person, can preferably reflect the development situation of atherosclerosis,
Therefore it can be used as the clinical diagnosis molecular marker of atherosclerosis, and be applied to preparation diagnosis or detection Atherosclerosis
The Related product of change, to enrich the diagnosis and detection means of atherosclerosis.
The generation of atherosclerosis and the exception of vascular endothelial cell have direct association.In atherosclerosis
In early days, due to the metabolic disorder of low-density lipoprotein, the inflammatory reaction of vascular endothelial cell can be caused, to promote endothelial cell
Secrete the inflammatory factors such as a large amount of adhesion factor, chemotactic factor (CF).The secretion of these inflammatory factors can promote monocyte and endothelium
Adhesive attraction between cell, so that monocyte passes through the endangium that endothelial cell gap enters subendothelial layer.Into
The low-density lipoprotein induction that monocyte after to inner membrance can be oxidized type becomes macrophage and swallows up lipophagia albumen, thus
Foam cells is gradually formed, the formation of plaque is eventually led to.Inventor further investigation revealed that, the artery is athero-
Hardening molecular marker is able to suppress the adhesive attraction between monocyte THP-1 and vascular endothelial cell HUVECs, and suppression
The expression of the inflammatory factors such as adhesion factor and chemotactic factor (CF) processed, to be effectively suppressed the excessive work of blood vessel endothelium inflammation
Change, therefore be also used as inhibiting the molecular drug target spot of formation and the development of atherosclerosis, for further research artery
The pathogenesis of atherosis explores its protective agents and provides new empirical theory basis and direction.
Detailed description of the invention
Fig. 1 is the peripheral blood mononuclear cells atherosclerosis molecular marker of Atheromatosis people and normal person
Expression quantity comparison;
Fig. 2 is comparison of the siRNA to the interference suppressioning effect of atherosclerosis molecular marker expression quantity;
Fig. 3 is that siRNA reduces the expression of atherosclerosis molecular marker to viscous between monocyte and endothelial cell
The influence of attached effect;
Fig. 4 is that the expression of siRNA reduction atherosclerosis molecular marker to adhesion factor VCAM1 and SELE and becomes
Change the influence of the expression quantity of factor M CP1 and IL8;
A is the overexpression Efficiency testing of atherosclerosis molecular marker as a result, B is to be overexpressed artery in Fig. 5 in Fig. 5
Influence of the atherosis molecular marker to adhesive attraction between monocyte and endothelial cell;
Fig. 6 is to be overexpressed atherosclerosis molecular marker to adhesion factor VCAM1 and SELE and chemotactic factor (CF)
The influence of the expression quantity of MCP1 and IL8.
Specific embodiment
To facilitate the understanding of the present invention, below will to invention is more fully described, and give it is of the invention compared with
Good embodiment.But the invention can be realized in many different forms, however it is not limited to embodiment described herein.Phase
Instead, purpose of providing these embodiments is makes the disclosure of the present invention more thorough and comprehensive.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the invention
The normally understood meaning of technical staff is identical.Term as used herein in the specification of the present invention is intended merely to description tool
The purpose of the embodiment of body, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more phases
Any and all combinations of the listed item of pass.
Atherosclerosis molecular marker and its application are made into one mainly in combination with specific embodiment and attached drawing below
Step detailed description.
One, the peripheral blood mononuclear cells atherosclerosis molecule of detection comparison normal person and Atheromatosis people
The expression quantity of marker
It is prepared by the separation of 1.1 peripheral blood mononuclear cells
Respectively from the lymph of normal person (10 as a control group) and Atheromatosis people (10 as experimental group)
Cell separating liquid (being purchased from the ocean Tianjin Hao biotech firm) separating periphery blood monocytic cell, draws intermediate tunica albuginea layer after centrifugation.So
It is washed twice afterwards with 0.9% sodium chloride solution, then cell is resuspended with the X-VIVO culture solution containing 10%PBS, and adjust cell
Concentration be 1 × 106A cell/mL.
The extraction of 1.2RNA
In the EP pipe for taking 50 μ L to 1.5mL of peripheral blood mononuclear cells respectively, the Trizol reagent of 500 μ L is added.Use liquid relief
Rifle pressure-vaccum is to after no longer sticky, into EP pipe plus 100 μ L chloroforms (1/5th of Trizol volume), sufficiently acutely after concussion
(becoming cloudy) stands 5min.12000rpm is centrifuged 10min, three layers is divided after centrifugation, for RNA in top layer, middle layer is albumen, most lower
Layer is organic phase.Supernatant to be drawn into new EP pipe, is added isometric isopropanol, concussion mixes, in -20 DEG C of placement 20min,
Keep RNA precipitate complete.12000rpm is centrifuged 10min, and supernatant is gone to leave precipitating, and the ethanol washing of 500 μ L 75% is added.Then
12000rpm is centrifuged 5min, removes supernatant, and repeated washing is primary.5~10min is placed at room temperature to dry, and 20 μ L DEPC water are added,
30min is dissolved at room temperature.
1.3 spectrophotometer measurement RNA concentration
Take 2 μ L RNA respectively, 198 μ L DEPC water be added, measured respectively in spectrophotometer after mixing OD230,
OD260 and OD280 assesses Nucleic acid quality, and obtains RNA concentration according to following calculation formula.
1.4 digest and remove the residual genomic DNA in RNA
For digesting 5 μ g RNA, 0.4 μ L RNase inhibitor (40U/ μ L), 1 μ L DNA are sequentially added
Enzyme, 2 μ 10 × deoxyribonuclease of L buffers and 5 μ g RNA, and DEPC water polishing is added to 20 μ L systems.It is then placed in
In PCR instrument, progress following procedure: 37 DEG C, 30min (deoxyribonuclease digests DNA);68 DEG C, 10min (makes deoxyribose
Nuclease-dead).
1.5 reverse transcription
By taking 1 μ g RNA of reverse transcription as an example, 4 μ L RNA (1 μ g), 2 μ L random primers (25 μM) and 6 μ L DEPC water are first added
Be configured to 12 μ L systems, PCR instrument be put into after mixing, program is as follows: 70 DEG C, 10min (opens complicated RNA structure);Then it stands
It is placed in 3~5min (RNA template is made to combine upper random primer) on ice.1 μ L dNTP (10mM), 4 are added in the above system
5 × RT Buffer of μ L, 0.5 μ L reverse transcriptase (MLV) and 2.5 μ L DEPC water, are put into PCR instrument, program is such as after mixing
Under: 30 DEG C, 10min;42 DEG C, 1h;70 DEG C, 15min.
1.6qRT-PCR detection
RNA sequence (the RefSeq sequence number: NR_131157.1, specific sequence of NKILA is found in ncbi database first
Column are as shown in SEQ ID NO.1), the sequence according to NKILA carries out design of primers and is synthesized, upstream and downstream primer (primer-F
With primer-R) sequence respectively as shown in SEQ ID NO.2 and SEQ ID NO.3.The cDNA that reverse transcription obtains is matched as template
Make following reaction system:
It is then placed in fluorescence quantitative PCR instrument and carries out following amplification program: 95 DEG C, 7min;40 circulations: 95 DEG C, 10s;
60 DEG C, 30s.Carry out melting curve analysis after amplification: 95 DEG C, 15s;60 DEG C, 15s;95 DEG C, 15s.Utilize 2-ΔΔCTRelatively
Sizing technique is compared analysis to the NKILA expression quantity in the peripheral blood mononuclear cells of normal person and Atheromatosis people.
As a result as shown in Figure 1, the expression quantity of NKILA obviously compares just in the peripheral blood mononuclear cells of Atheromatosis people
The expression quantity of NKILA wants low (* represents P value ﹤ 0.05 in figure) in the peripheral blood mononuclear cells of ordinary person.
Two, the design of atherosclerosis molecular marker siRNA sequence and its detection of interference effect
RNA interference (RNAi) technology refer to it is being highly conserved during evolution, induced by double-chain small molecule RNA it is homologous
The phenomenon that mRNA efficient selective degradation, RNA molecule is by destroying specific mRNA, to inhibit the biology mistake of certain gene expression
Journey.It is a kind of gene silencing process of sequence specific post transcriptional level being widely present in animals and plants, is biological gene
Group resists a kind of biological protection mechanism of the external hereditary original part invasion of virus etc.Due to using RNAi technology can specificity
The expression of specific gene is rejected or closes, which rapidly becomes gene functional research and gene therapy research field is of greatest concern
One of research tool, have been widely used for the biological function for exploring gene and the treatment of various diseases.
2.1 design siRNA
According to the RNA complete sequence (as shown in SEQ ID NO.1) of NKILA using siRNA design website (http: //
Sidirect2.rnai.jp/), design siRNA sequence and screened, marine growth Sheng Gong company synthesizes in commission, the siRNA
Sense strand and antisense strand particular sequence respectively as shown in SEQ ID NO.4 and SEQ ID NO.5.
2.2 detect the interference effect of above-mentioned siRNA using huve cell (HUVECs)
By in HUVECs cell inoculation to six orifice plates, reaches 70% or so to cell density, utilize Lipofectamine
3000 transfection reagents are respectively by control group siRNA (particular sequence is as shown in SEQ ID NO.6 and SEQ ID NO.7) and above-mentioned reality
A group siRNA is tested to be transfected into HUVECs.
Steps are as follows for the specific method of transfection siRNA: the serum free medium of 150 μ L being taken to be added to two 1.5mL's respectively
In EP pipe, the Lipofectamine 3000 of 6 μ L is taken to be added thereto in an EP pipe, it is dense that 6 μ L are added in another EP pipe
The siRNA that degree is 10 μM.The mixture of siRNA culture medium is added to the mixture of 3000 culture medium of Lipofectamine
In, vortex oscillation 5 seconds, it is mixed well, is added dropwise in HUVECs cell after the static 10min of room temperature.After 6 hours more
Renew fresh complete medium, after 48 hours, carries out reverse transcription using Trizol extracted total RNA as previously described and pass through fluorescence
Quantitative PCR carries out the rna expression amount detection of NKILA.
As a result as shown in Fig. 2, the expression quantity of the NKILA in experimental group cell is significantly lower than the NKILA in cellular control unit
Expression quantity (* * * represents P value ﹤ 0.001 in figure), illustrate designed siRNA can selectively targeted NKILA, make its expression
Amount reduces, therefore the siRNA can be used for further exploring the biological function of NKILA and the treatment of atherosclerosis.
Three, influence of the expression quantity of atherosclerosis molecular marker to blood vessel endothelium inflammation is reduced
Inflammatory reaction is a kind of clinically very common pathological reaction, refers to the living tissue with vascular system to each
A kind of basic pathology process based on defense reaction that the stimulation of kind damage factor is occurred.Inflammation often show as it is red, swollen,
Heat, pain and dysfunction, also with general reactions such as fever, the changes of tip Leukocyte Counts.The overactivity of inflammation and dynamic
Generation, the development of pulse atherosclerosis are closely bound up.
3.1 reduce influence of the expression quantity to adhering between monocyte and endothelial cell
Blood vessel endothelium inflammation can promote some relevant adhesion factors of endothelial cells secrete to promote monokaryon after being activated
Adhesive attraction between cell and endothelial cell, so endothelial cell can be reacted by the adhesive attraction between verifying cell
Degree of inflammation, specific step is as follows.
Endothelial cell HUVECs is inoculated into 6 orifice plates, overnight, when density reaches 80%, utilizes Lipofectamine
Control group siRNA and experimental group siRNA are transfected into HUVECs (for example preceding institute of specific transfection procedure by 3000 transfection reagents respectively
It states).Fresh culture is changed within 6 hours after transfection into, after transfection 48 hours, by monocyte THP-1 Tracker Green
CMFDA carries out the label of fluorophor, changes fresh culture medium after 1 hour into HUVECs, while being washed with RPMI culture medium
THP-1 cell 3 times.THP-1 cell is added separately in control group and the HUVECs of experimental group, it is small to be put into incubator incubation 1
When.It is washed 3 times with the ECM culture medium of culture HUVECs cell, removes the THP-1 cell being not adhered on HUVECs, in fluorescence
The THP-1 cell adhered on HUVECs is counted and taken pictures under microscope.
As a result as shown in figure 3, it can be seen from the figure that compared with the control group, after the expression quantity for reducing NKILA, THP-1
Adhesive attraction between HUVECs cell has obtained significant enhancing.
3.2 reduce the influence of inflammatory factor expression amount in expression quantity Human Umbilical Vein Endothelial Cells
By in HUVECs cell inoculation to six orifice plates, reaches 70% or so to cell density, utilize Lipofectamine
Control group siRNA and experimental group siRNA are transfected into HUVECs by 3000 transfection reagents respectively.After 48 hours, utilize
Trizol extracted total RNA carries out reverse transcription and by quantitative fluorescent PCR to adhesion factor VCAM1 and SELE and chemotactic factor (CF)
The mrna expression amount of four kinds of inflammatory factors such as MCP1 and IL8 is detected.
As a result as shown in figure 4, after the expression quantity of NKILA reduces, adhesion factor VCAM1 and SELE and chemotactic factor (CF)
Significantly (* * represents P value ﹤ 0.01 to the expression quantity of the inflammatory factors such as MCP1 and IL8 in figure, and * * * represents P value ﹤ in figure for raising
0.001)。
Four, atherosclerosis molecular marker is overexpressed the influence to blood vessel endothelium inflammation
The Lentiviral of 4.1 building atherosclerosis molecular markers
According to the RNA sequence of above-mentioned NKILA, the DNA sequence dna of double-strand is synthesized, and takes BamH I respectively at starting both ends
With two restriction enzyme sites of Xba I.By the double digestion in the two sites BamH I and Xba I, the NKILA of synthesis is passed through into DNA
T4 ligase is connected on the slow virus empty carrier of pLV CS2.0 (slow virus empty carrier sequence is as shown in SEQ ID NO.8).
Endonuclease reaction system are as follows:
After adding water polishing to 20 μ L, it is placed on 37 DEG C and is incubated for 4 hours.
T4 DNA ligase reaction system are as follows:
10 × buffer, 1 μ L
NKILA segment: pLV carrier (molal quantity) (1~5): 1
1 μ L of T4 ligase
After adding water polishing to 10 μ L, it is placed in 16 DEG C of overnight incubations.
Slow virus packaging is carried out respectively to pLV CS2.0 empty carrier and NKILA over-express vector, the specific steps are as follows: will
HEK293T cell inoculation reaches 70% into 6 orifice plates, to cell density, using Lipofectamine 3000 respectively by NKILA
It is thin that overexpression plasmid and the empty carrier of control and slow virus the packaging plasmid pSPAX2 and pMD2G of commercialization are transfected into HEK293T
In born of the same parents, plasmid is specifically matched are as follows:
pSPAX2 0.5μg
pMD2G 0.5μg
NKILA is overexpressed plasmid or 1 μ g of empty carrier
After 48 hours to be transfected, viral supernatants are collected, infection cell is can be directly used for or freezes in minus 80 degree of ultralow temperature ices
Case, in case using.
4.2 detections are overexpressed the influence to adhering between monocyte and endothelial cell.
Huve cell HUVECs is inoculated into six orifice plates, reaches 80% to cell density, discards former culture medium,
It takes above-mentioned empty carrier (vec) and NKILA to be overexpressed virus (NKILA-flag) supernatant 1mL respectively, is added in HUVECs, and add
The fresh culture of 1mL is eventually adding the polybrene (Polybrene) that 2 μ L concentration are 4 μ g/ μ L.After 8 hours, changed to cell
At fresh culture medium.After infecting 48 hours, by the processing of inducer TNF α 1 hour of HUVECs cell inflammatory reaction, together
When monocyte THP-1 is carried out to the label of fluorophor with Tracker Green CMFDA, be placed in 37 DEG C and be incubated for 1 hour.With
ECM culture medium washs HUVECs 3 times and changes fresh ECM culture medium into, while washing THP-1 cell 3 with RPMI culture medium
It is secondary.It is added separately to the THP-1 cell that Tracker Green is marked to have infected empty carrier and NKILA is overexpressed slow virus
HUVECs in, be put into incubator be incubated for 1 hour.It is washed 3 times, is removed nonadherent with the ECM culture medium of culture HUVECs cell
THP-1 cell on to HUVECs is counted and is clapped to the THP-1 cell adhered on HUVECs under fluorescence microscope
According to.
As shown in Figure 5A, compared with the control group of infection empty carrier, the experimental group after infection NKILA overexpression slow virus is thin
The expression quantity of NKILA dramatically increases (* * * represents P value ﹤ 0.001 in figure) in born of the same parents.Importantly, as shown in Figure 5 B, NKILA's
The adhesive attraction between monocyte THP-1 and endothelial cell HUVECs is significantly suppressed after expression quantity increase.
4.3 detections are overexpressed the influence to inflammatory factor in vascular endothelial cell
HUVECs is inoculated into 6 orifice plates, reaches 80% to cell density, respectively with packaged empty carrier and NKILA
It is overexpressed slow-virus infection HUVECs.After infection HUVECs 48 hours, handled 1 hour with the inducer TNF α of inflammatory reaction.With
Trizol lytic cell extract total serum IgE, after dnase digestion, take 1 μ g RNA carry out reverse transcription, by the cDNA after reverse transcription into
Row quantitative fluorescent PCR, detection infection empty carrier and NKILA are overexpressed the expression quantity of relevant inflammatory factors after slow virus respectively.
As a result as shown in fig. 6, compared with the control group of infection empty carrier, infection NKILA is overexpressed the experiment after slow virus
In group cell, the expression quantity of the inflammatory factors such as adhesion factor VCAM1 and SELE and chemotactic factor (CF) MCP1 and IL8 is all significantly reduced
(* represents P value ﹤ 0.05 in figure, and * * represents P value ﹤ 0.01 in figure), again demonstrates long-chain non-coding RNA NKILA to intravascular
The important inhibiting effect of dermatitis disease.
In summary, long-chain non-coding RNA NKILA (sequence is as shown in SEQ ID NO.1) is in Atheromatosis people
Peripheral blood mononuclear cells in expression quantity significantly lower than normal person peripheral blood mononuclear cells in expression quantity (P value <
0.05) it, can preferably reflect the development situation of atherosclerosis, therefore can be used as the clinical diagnosis point of atherosclerosis
Sub- marker, and it is applied to the Related product of preparation diagnosis or detection atherosclerosis, to enrich atherosclerosis
Diagnosis and detection means.The atherosclerosis molecular marker is able to suppress monocyte THP-1 and vascular endothelial cell
Adhesive attraction between HUVECs, and inhibit the expression of the inflammatory factors such as adhesion factor and chemotactic factor (CF), to be able to effectively
Ground inhibits the overactivity of blood vessel endothelium inflammation, therefore is also used as inhibiting the molecule of formation and the development of atherosclerosis
Drug target is the pathogenesis of further studying atherosclerotic, explores its protective agents and provide new empirical theory base
Plinth and direction.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Sequence table
<110>Xinxiang College of Medical Science
<120>atherosclerosis molecular marker and its application
<160> 8
<170> SIPOSequenceListing 1.0
<210> 1
<211> 2615
<212> RNA
<213> Homo sapiens
<400> 1
agacccggca cccgcgcaac ggaggagggg cgcugugccc ucuccccaac ggcggucagc 60
uuggaacgcc ugcccggcgc acgcccgggg ccggggagcc gaacucggug ccagccgcac 120
ccgggcgggu ugcuggugcg cccuccccuc gcccccgucc cugggguccu ugacccaggc 180
ucuuggggcu agccuaucuu cugaggagca caaggucccu gggggcucag ggaagagaaa 240
uuggagaaag ggggaggaag cccccaagau ggaucaccca uugccugguu ucgcaggaga 300
cuguccgccu ucaguucucc agcagcucgg ggaucauggc ccacugaacc cccaagcgcu 360
uucacccgaa cccaaggagg acgaccagga aagacgggaa cucgcguaga cacgcccgga 420
agcccuuguc auguaaauag cugucgggga cugguguauu gucgccgccc cagccggcgg 480
gaccuggggc gaauccacac ccauugucug cugcccaagg ggccuccggc uggggggcgc 540
ggcugcggag uucaaaaggg guaugagcag gaggggugua cuuuuaguuc auuaaguuuu 600
aauuacagga gugcuacaag aacacauucu ucagguuuaa aaagauauua aaauauuaca 660
uaagagaccu ccccucccug gcccaccucc agccucuuaa aaauuuagug ugucgccuuu 720
uagacacuuu cucaaagcuu cacuuauuua acaggcacuu aaggagcacc uaccugugcc 780
agaaacucuc caaauauuaa cucaaccuga caccgacuca guguggccga auauuacucu 840
ccccauuuua cagagcgggc agcuggucaa ggaagucgcu uguugaaagu cacacagugg 900
uggagccugu gugccaaccc aggacccugg ggagcugccu cccccucucc cacguagucc 960
ugauucuuua aguguccaca uauuccugua augccuggag uuucaguaau uagcagggac 1020
uuaguguguu cagagaaaaa aaaagcuuuu aaaaauuauu guuacugugu uuguaacagu 1080
uuggauagag aaggaaaagc uggaauuugg gaagugaagg uggccucggg guagaacuua 1140
ccuagaccag agcgaauuca uccugaagaa cucagagaaa gccggugcag gaaguggguu 1200
cccgcucucc cugcacaggc acagugaugc ugccagagcu cucccagaaa gaccaggagg 1260
cuuguucugg agaagucaag cccagggaug uggcucaggc ugguccaagc ucuuuggagg 1320
aguccaagcg ugcccagccc agagggaggu ucagaggcac ugaccgucuu cuguuuggga 1380
ggagaagcuc acucuuggag ccacagccag cacuagguca ggacccaggc cccggcccag 1440
gaguggggca auacccagcg ucuaccccag auggcacccu gcugugaacu gggcgcccuc 1500
agccccugcc uugaggaagg ggcaauacca ccagcguguc uuuuaucagg gaagauauug 1560
cugcaguuug gccgcugcaa cuuaagagaa aagcuaaggg gucccccagc aucccuuggg 1620
gugccacugc aaauacuggc ugggccugga gaugaccugg gucccauuca cuuccuaggg 1680
ugaaggaggu caucauuacc accccugcuu ucagccauuu cuucauucau ucaaucaaca 1740
aacuggcuga gcugcaaccc ugagccgggg aauucagcca cuccagacac agccccugcc 1800
cuccgggaag ucucgggaga ccuggcuagu cuggcuggga gaagucacac guugauuguc 1860
uuggaaguga gauggcauuu acacaaugga ggcugcacug ccagcaggca aaaauaacca 1920
guuaauucag uggcuuaaag aaaccaaacc uacccacaac gcuugaccuc ccauugaucc 1980
aucugcgaca ccggcagugg cuaccauuua uugagugcug auggugucac cugggauuga 2040
cuuagugguc ucuggcgcua guuccgaagu ugauucuguc uggagagcuu aaugcagugu 2100
ucagaccuca ggguccgaac cugaggguca cccaaagaug agugggacau agcuguguga 2160
ccucggcuga gugcuuucac cucuccaacc ucaguuuccu cuucugcaaa augggguggc 2220
uucauggcac cuucacgugg ugugauugcg aggaaugaag ggaucgaugc cuugcaagua 2280
gaggagaagg ggccggauac aucuuaguug uuauguuauu uaaucaucuu ggcaaccccg 2340
ggagggagga accacuauca uuuuauuuuc cauuuugcag uugaggacaa ugaugauucc 2400
agcacagaca gggccccuga cggggcagua ggaaaggaga auugcuuugg aaggagcaua 2460
ggcuggacug ccagcacuca uaggaggcuu cgugugugcc caggacugcg agaauuaaau 2520
acaggacacc caguucaguu ugaauuucag auaaacuaug aauaaugauu aguguaagua 2580
uaucucaauu uaacuggaaa aaaaaaaaaa aaaaa 2615
<210> 2
<211> 20
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 2
aaccaaacct acccacaacg 20
<210> 3
<211> 22
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 3
accactaagt caatcccagg tg 22
<210> 4
<211> 19
<212> RNA
<213>artificial sequence (Artificial Sequence)
<400> 4
gggcaguagg aaaggagaa 19
<210> 5
<211> 19
<212> RNA
<213>artificial sequence (Artificial Sequence)
<400> 5
uucuccuuuc cuacugccc 19
<210> 6
<211> 21
<212> RNA
<213>artificial sequence (Artificial Sequence)
<400> 6
gcaagcugac ccugaaguuc a 21
<210> 7
<211> 21
<212> RNA
<213>artificial sequence (Artificial Sequence)
<400> 7
ugaacuucag ggucagcuug c 21
<210> 8
<211> 8865
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 8
aagcttaatg tagtcttatg caatactctt gtagtcttgc aacatggtaa cgatgagtta 60
gcaacatgcc ttacaaggag agaaaaagca ccgtgcatgc cgattggtgg aagtaaggtg 120
gtacgatcgt gccttattag gaaggcaaca gacgggtctg acatggattg gacgaaccac 180
tgaattgccg cattgcagag atattgtatt taagtgccta gctcgataca taaacgggtc 240
tctctggtta gaccagatct gagcctggga gctctctggc taactaggga acccactgct 300
taagcctcaa taaagcttgc cttgagtgct tcaagtagtg tgtgcccgtc tgttgtgtga 360
ctctggtaac tagagatccc tcagaccctt ttagtcagtg tggaaaatct ctagcagtgg 420
cgcccgaaca gggacttgaa agcgaaaggg aaaccagagg agctctctcg acgcaggact 480
cggcttgctg aagcgcgcac ggcaagaggc gaggggcggc gactggtgag tacgccaaaa 540
attttgacta gcggaggcta gaaggagaga gatgggtgcg agagcgtcag tattaagcgg 600
gggagaatta gatcgcgatg ggaaaaaatt cggttaaggc cagggggaaa gaaaaaatat 660
aaattaaaac atatagtatg ggcaagcagg gagctagaac gattcgcagt taatcctggc 720
ctgttagaaa catcagaagg ctgtagacaa atactgggac agctacaacc atcccttcag 780
acaggatcag aagaacttag atcattatat aatacagtag caaccctcta ttgtgtgcat 840
caaaggatag agataaaaga caccaaggaa gctttagaca agatagagga agagcaaaac 900
aaaagtaaga ccaccgcaca gcaagcggcc gctgatcttc agacctggag gaggagatat 960
gagggacaat tggagaagtg aattatataa atataaagta gtaaaaattg aaccattagg 1020
agtagcaccc accaaggcaa agagaagagt ggtgcagaga gaaaaaagag cagtgggaat 1080
aggagctttg ttccttgggt tcttgggagc agcaggaagc actatgggcg cagcgtcaat 1140
gacgctgacg gtacaggcca gacaattatt gtctggtata gtgcagcagc agaacaattt 1200
gctgagggct attgaggcgc aacagcatct gttgcaactc acagtctggg gcatcaagca 1260
gctccaggca agaatcctgg ctgtggaaag atacctaaag gatcaacagc tcctggggat 1320
ttggggttgc tctggaaaac tcatttgcac cactgctgtg ccttggaatg ctagttggag 1380
taataaatct ctggaacaga tttggaatca cacgacctgg atggagtggg acagagaaat 1440
taacaattac acaagcttaa tacactcctt aattgaagaa tcgcaaaacc agcaagaaaa 1500
gaatgaacaa gaattattgg aattagataa atgggcaagt ttgtggaatt ggtttaacat 1560
aacaaattgg ctgtggtata taaaattatt cataatgata gtaggaggct tggtaggttt 1620
aagaatagtt tttgctgtac tttctatagt gaatagagtt aggcagggat attcaccatt 1680
atcgtttcag acccacctcc caaccccgag gggacccgac aggcccgaag gaatagaaga 1740
agaaggtgga gagagagaca gagacagatc cattcgatta gtgaacggat ctcgacggta 1800
tcggttaact tttaaaagaa aaggggggat tggggggtac agtgcagggg aaagaatagt 1860
agacataata gcaacagaca tacaaactaa agaattacaa aaacaaatta caaaattcaa 1920
aattttatcg atgcctcccc gtcaccaccc cccccaaccc gccccgaccg gagctgagag 1980
taattcatac aaaaggactc gcccctgcct tggggaatcc cagggaccgt cgttaaactc 2040
ccactaacgt agaacccaga gatcgctgcg ttcccgcccc ctcacccgcc cgctctcgtc 2100
atcactgagg tggagaagag catgcgtgag gctccggtgc ccgtcagtgg gcagagcgca 2160
catcgcccac agtccccgag aagttggggg gaggggtcgg caattgaacc ggtgcctaga 2220
gaaggtggcg cggggtaaac tgggaaagtg atgtcgtgta ctggctccgc ctttttcccg 2280
agggtggggg agaaccgtat ataagtgcag tagtcgccgt gaacgttctt tttcgcaacg 2340
ggtttgccgc cagaacacag gtaagtgccg tgtgtggttc ccgcgggcct ggcctcttta 2400
cgggttatgg cccttgcgtg ccttgaatta cttccacgcc cctggctgca gtacgtgatt 2460
cttgatcccg agcttcgggt tggaagtggg tgggagagtt cgaggccttg cgcttaagga 2520
gccccttcgc ctcgtgcttg agttgaggcc tggcctgggc gctggggccg ccgcgtgcga 2580
atctggtggc accttcgcgc ctgtctcgct gctttcgata agtctctagc catttaaaat 2640
ttttgatgat atcctgcgac gctttttttc tggcaagata gtcttgtaaa tgcgggccaa 2700
gatctgcaca ctggtatttc ggtttttggg gccgcgggcg gcgacggggc ccgtgcgtcc 2760
cagcgcacat gttcggcgag gcggggcctg cgagcgcggc caccgagaat cggacggggg 2820
tagtctcaag ctggccggcc tgctctggtg cctggcctcg cgccgccgtg tatcgccccg 2880
ccctgggcgg caaggctggc ccggtcggca ccagttgcgt gagcggaaag atggccgctt 2940
cccggccctg ctgcagggag ctcaaaatgg aggacgcggc gctcgggaga gcgggcgggt 3000
gagtcaccca cacaaaggaa aagggccttt ccgtcctcag ccgtcgcttc atgtgactcc 3060
acggagtacc gggcgccgtc caggcacctc gattagttct cgagcttttg gagtacgtcg 3120
tctttaggtt ggggggaggg gttttatgcg atggagtttc cccacactga gtgggtggag 3180
actgaagtta ggccagcttg gcacttgatg taattctcct tggaatttgc cctttttgag 3240
tttggatctt ggttcattct caagcctcag acagtggttc aaagtttttt tcttccattt 3300
caggtgtcgt gaaaactacc cctgagctcc ttaaggttaa cgccaccatg gactacaaag 3360
acgatgacga caagtctaga gaattcggat ccaatattcc cgggctcgag ccatggaagc 3420
ttgatatcta actgactgaa ccggtggtac cgatccacgc gtctccggcc tagggataac 3480
agggtaatcc gctagcccct ctccctcccc cccccctaac gttactggcc gaagccgctt 3540
ggaataaggc cggtgtgcgt ttgtctatat gttattttcc accatattgc cgtcttttgg 3600
caatgtgagg gcccggaaac ctggccctgt cttcttgacg agcattccta ggggtctttc 3660
ccctctcgcc aaaggaatgc aaggtctgtt gaatgtcgtg aaggaagcag ttcctctgga 3720
agcttcttga agacaaacaa cgtctgtagc gaccctttgc aggcagcgga accccccacc 3780
tggcgacagg tgcctctgcg gccaaaagcc acgtgtataa gatacacctg caaaggcggc 3840
acaaccccag tgccacgttg tgagttggat agttgtggaa agagtcaaat ggctctcctc 3900
aagcgtattc aacaaggggc tgaaggatgc ccagaaggta ccccattgta tgggatctga 3960
tctggggcct cggtacacat gctttacatg tgtttagtcg aggttaaaaa aacgtctagg 4020
ccccccgaac cacggggacg tggttttcct ttgaaaaaca cgatgataat atggccacac 4080
tagagatcca ccggtcgcca ccatgaccga gtacaagccc acggtgcgcc tcgccacccg 4140
cgacgacgtc cccagggccg tacgcaccct cgccgccgcg ttcgccgact accccgccac 4200
gcgccacacc gtcgatccgg accgccacat cgagcgggtc accgagctgc aagaactctt 4260
cctcacgcgc gtcgggctcg acatcggcaa ggtgtgggtc gcggacgacg gcgccgcggt 4320
ggcggtctgg accacgccgg agagcgtcga agcgggggcg gtgttcgccg agatcggccc 4380
gcgcatggcc gagttgagcg gttcccggct ggccgcgcag caacagatgg aaggcctcct 4440
ggcgccgcac cggcccaagg agcccgcgtg gttcctggcc accgtcggcg tctcgcccga 4500
ccaccagggc aagggtctgg gcagcgccgt cgtgctcccc ggagtggagg cggccgagcg 4560
cgccggggtg cccgccttcc tggagacctc cgcgccccgc aacctcccct tctacgagcg 4620
gctcggcttc accgtcaccg ccgacgtcga ggtgcccgaa ggaccgcgca cctggtgcat 4680
gacccgcaag cccggtgcct gagcggccgc gtcgacaatc aacctctgga ttacaaaatt 4740
tgtgaaagat tgactggtat tcttaactat gttgctcctt ttacgctatg tggatacgct 4800
gctttaatgc ctttgtatca tgctattgct tcccgtatgg ctttcatttt ctcctccttg 4860
tataaatcct ggttgctgtc tctttatgag gagttgtggc ccgttgtcag gcaacgtggc 4920
gtggtgtgca ctgtgtttgc tgacgcaacc cccactggtt ggggcattgc caccacctgt 4980
cagctccttt ccgggacttt cgctttcccc ctccctattg ccacggcgga actcatcgcc 5040
gcctgccttg cccgctgctg gacaggggct cggctgttgg gcactgacaa ttccgtggtg 5100
ttgtcgggga agctgacgtc ctttccatgg ctgctcgcct gtgttgccac ctggattctg 5160
cgcgggacgt ccttctgcta cgtcccttcg gccctcaatc cagcggacct tccttcccgc 5220
ggcctgctgc cggctctgcg gcctcttccg cgtcttcgcc ttcgccctca gacgagtcgg 5280
atctcccttt gggccgcctc cccgcctgga attcgagctc ggtaccttta agaccaatga 5340
cttacaaggc agctgtagat cttagccact ttttaaaaga aaagggggga ctggaagggc 5400
taattcactc ccaacgaaga caagatctgc tttttgcttg tactgggtct ctctggttag 5460
accagatctg agcctgggag ctctctggct aactagggaa cccactgctt aagcctcaat 5520
aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac tctggtaact 5580
agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtagt agttcatgtc 5640
atcttattat tcagtattta taacttgcaa agaaatgaat atcagagagt gagaggaact 5700
tgtttattgc agcttataat ggttacaaat aaagcaatag catcacaaat ttcacaaata 5760
aagcattttt ttcactgcat tctagttgtg gtttgtccaa actcatcaat gtatcttatc 5820
atgtctggct ctagctatcc cgcccctaac tccgcccatc ccgcccctaa ctccgcccag 5880
ttccgcccat tctccgcccc atggctgact aatttttttt atttatgcag aggccgaggc 5940
cgcctcggcc tctgagctat tccagaagta gtgaggaggc ttttttggag gcctagggac 6000
gtacccaatt cgccctatag tgagtcgtat tacgcgcgct cactggccgt cgttttacaa 6060
cgtcgtgact gggaaaaccc tggcgttacc caacttaatc gccttgcagc acatccccct 6120
ttcgccagct ggcgtaatag cgaagaggcc cgcaccgatc gcccttccca acagttgcgc 6180
agcctgaatg gcgaatggga cgcgccctgt agcggcgcat taagcgcggc gggtgtggtg 6240
gttacgcgca gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc tttcgctttc 6300
ttcccttcct ttctcgccac gttcgccggc tttccccgtc aagctctaaa tcgggggctc 6360
cctttagggt tccgatttag tgctttacgg cacctcgacc ccaaaaaact tgattagggt 6420
gatggttcac gtagtgggcc atcgccctga tagacggttt ttcgcccttt gacgttggag 6480
tccacgttct ttaatagtgg actcttgttc caaactggaa caacactcaa ccctatctcg 6540
gtctattctt ttgatttata agggattttg ccgatttcgg cctattggtt aaaaaatgag 6600
ctgatttaac aaaaatttaa cgcgaatttt aacaaaatat taacgcttac aatttaggtg 6660
gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa 6720
atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga 6780
agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc 6840
ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg 6900
gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc 6960
gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt ggcgcggtat 7020
tatcccgtat tgacgccggg caagagcaac tcggtcgccg catacactat tctcagaatg 7080
acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag 7140
aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa 7200
cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc 7260
gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca 7320
cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc 7380
tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc 7440
tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg 7500
ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta 7560
tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag 7620
gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga 7680
ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc 7740
tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa 7800
agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa 7860
aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc 7920
cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgttcttcta gtgtagccgt 7980
agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc 8040
tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac 8100
gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca 8160
gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg 8220
ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag 8280
gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt 8340
ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat 8400
ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc 8460
acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt 8520
gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag 8580
cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca 8640
gctggcacga caggtttccc gactggaaag cgggcagtga gcgcaacgca attaatgtga 8700
gttagctcac tcattaggca ccccaggctt tacactttat gcttccggct cgtatgttgt 8760
gtggaattgt gagcggataa caatttcaca caggaaacag ctatgaccat gattacgcca 8820
agcgcgcaat taaccctcac taaagggaac aaaagctgga gctgc 8865
Claims (10)
1. a kind of atherosclerosis molecular marker, which is characterized in that the atherosclerosis molecular marker is long-chain
Non-coding RNA has the nucleotide sequence as shown in SEQ ID NO.1.
2. a kind of PCR amplification primer, which is characterized in that including being used for specific amplification Atherosclerosis described in claim 1
The upstream primer and downstream primer of chemoattractant molecule marker.
3. PCR amplification primer according to claim 2, which is characterized in that the upstream primer has such as SEQ ID NO.2
Shown in nucleotide sequence, the downstream primer have the nucleotide sequence as shown in SEQ ID NO.3.
4. a kind of siRNA, which is characterized in that including complementary sense strand and antisense strand, and the siRNA can be special
Inhibit the expression of atherosclerosis molecular marker described in claim 1 anisotropicly.
5. siRNA according to claim 4, which is characterized in that the sense strand has as shown in SEQ ID NO.2
Nucleotide sequence, the antisense strand have the nucleotide sequence as shown in SEQ ID NO.3.
6. PCR described in any one of atherosclerosis molecular marker as described in claim 1, claim 2~3 expands
Increase siRNA described in any one of primer or claim 4~5 in preparation diagnosis or the product of detection atherosclerosis
In application.
7. application according to claim 6, which is characterized in that the product be detection reagent, kit, genetic chip or
Test paper.
8. PCR described in any one of atherosclerosis molecular marker as described in claim 1, claim 2~3 expands
Increase siRNA described in any one of primer or claim 4~5 in preparation for preventing or treating atherosclerosis
Application in drug.
9. a kind of for detecting the kit of atherosclerosis, which is characterized in that expand including PCR described in claim 2 or 3
Increase primer.
10. kit according to claim 9, which is characterized in that further include that RNA extracts reagent, reverse transcription reagents and PCR
At least one of amplifing reagent.
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CN109182503A (en) * | 2018-09-28 | 2019-01-11 | 新乡医学院 | Atherosclerosis molecular marker and its application |
CN110283906A (en) * | 2019-08-12 | 2019-09-27 | 徐州医科大学 | Mankind's early atherosclerosis detection molecules marker and its application |
CN110791501A (en) * | 2019-08-02 | 2020-02-14 | 哈尔滨医科大学 | Long-chain non-coding RNA and application of interference RNA thereof in treatment of atherosclerosis |
CN111458512A (en) * | 2019-01-21 | 2020-07-28 | 中国科学院分子细胞科学卓越创新中心 | Atherosclerosis biomarker and application thereof |
CN114672550A (en) * | 2022-05-05 | 2022-06-28 | 青岛大学 | Atherosclerosis biomarker and inhibitor and application thereof |
CN114807348A (en) * | 2022-04-21 | 2022-07-29 | 济南大学 | Long-chain non-coding RNA LRA-1 and application of interference RNA thereof in treatment of atherosclerosis |
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CN109182503A (en) * | 2018-09-28 | 2019-01-11 | 新乡医学院 | Atherosclerosis molecular marker and its application |
CN111458512A (en) * | 2019-01-21 | 2020-07-28 | 中国科学院分子细胞科学卓越创新中心 | Atherosclerosis biomarker and application thereof |
CN110791501A (en) * | 2019-08-02 | 2020-02-14 | 哈尔滨医科大学 | Long-chain non-coding RNA and application of interference RNA thereof in treatment of atherosclerosis |
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CN110283906A (en) * | 2019-08-12 | 2019-09-27 | 徐州医科大学 | Mankind's early atherosclerosis detection molecules marker and its application |
CN114807348A (en) * | 2022-04-21 | 2022-07-29 | 济南大学 | Long-chain non-coding RNA LRA-1 and application of interference RNA thereof in treatment of atherosclerosis |
CN114807348B (en) * | 2022-04-21 | 2024-05-07 | 济南大学 | Application of long-chain non-coding RNA LRA-1 and interfering RNA thereof in treatment of atherosclerosis |
CN114672550A (en) * | 2022-05-05 | 2022-06-28 | 青岛大学 | Atherosclerosis biomarker and inhibitor and application thereof |
CN114672550B (en) * | 2022-05-05 | 2023-11-17 | 青岛大学 | Atherosclerosis biomarker and inhibitor and application thereof |
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