CN116687950A - Application of miR-194-3p in preparation of medicine for treating diabetic cardiomyopathy - Google Patents
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Abstract
The invention belongs to the technical field of diabetes metabolic treatment, and relates to application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy. The miR-194-3p overexpression can obviously improve the left ventricular diastolic function of a diabetic mouse and the myocardial fibrosis of the mouse, obviously reduce the fibrosis area and reverse the myocardial fibrosis of the diabetes.
Description
Technical Field
The invention belongs to the technical field of diabetes metabolic treatment, and particularly relates to application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy.
Background
Diabetes mellitus has a close relationship with cardiovascular diseases as two important diseases of chronic non-infectious diseases. Diabetes is an important risk factor for cardiovascular disease, while cardiovascular complications are one of the major chronic complications and the most leading cause of death in diabetes. Diabetic cardiomyopathy, including impaired cardiac structure and function, has been found to cause serious cardiac dysfunction, and even through enhanced glycemic control, does not improve cardiac function or reduce risk of heart failure. However, the conventional treatment of heart failure is irrelevant to whether a patient suffers from diabetes, and no accurate treatment scheme for the heart failure related to the diabetes exists at present.
One of the major hallmarks of diabetic cardiomyopathy is Left Ventricular (LV) diastolic dysfunction, which is the first sign of diabetic cardiomyopathy, usually occurs earlier than clinically significant left ventricular systolic dysfunction. There is much evidence that diabetic patients have cardiac fibrosis, and immunohistochemical staining of myocardial tissue reveals that type I and type III interstitial collagen deposition in myocardial tissue of diabetic patients is significantly increased, and interstitial and perivascular fibrosis is also significantly increased. Non-invasive detection using echocardiography, nuclear magnetic resonance, and the like also reveals that diabetic cardiomyopathy exists. These evidence suggest that diabetic cardiomyopathy is associated with increased cardiac fibrosis.
Almost all cardiac causes involve pathological myocardial remodeling characterized by excessive deposition of extracellular matrix (ECM) and fibroblasts (CFs) by the heart and reduced tissue compliance. In this pathological process, fibroblasts are the necessary cell types. Physiologically, fibroblasts are responsible for the homeostasis of the extracellular matrix, which provides structural scaffolds for Cardiomyocytes (CM), distributes mechanical forces and mediates electrical conduction. Unlike other organs, the heart has very limited capacity to regenerate itself after injury, and the repair process mainly involves removal of necrotic cardiomyocytes followed by fibrotic scar tissue replacement to preserve the structural and functional integrity of the heart muscle. Fibroblasts in connective tissue are transformed into myofibroblasts, which secrete extracellular matrix proteins to promote the fibrotic environment. Cardiac fibrosis causes a range of pathological changes including ventricular dilatation, cardiomyocyte hypertrophy, apoptosis, etc., ultimately leading to the occurrence of congestive heart failure. At present, the mechanism of transformation from cardiac fibroblasts to myofibroblasts is not clear in the diabetic state, and no drug capable of reversing diabetic myocardial fibrosis is clinically available.
Disclosure of Invention
The invention aims to provide an application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy. The miR-194-3p overexpression can obviously improve the left ventricular diastolic function of a diabetic mouse and the myocardial fibrosis of the mouse, obviously reduce the fibrosis area and reverse the myocardial fibrosis of the diabetes.
The invention provides application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy.
The invention also provides application of miR-194-3p in preparation of a medicament for treating diabetic myocardial fibrosis.
The invention also provides application of miR-194-3p in preparation of a medicament for improving diabetic left ventricular diastolic dysfunction.
The invention also provides application of miR-194-3p in preparation of a medicament for reducing the myocardial fibrosis area of diabetes.
Preferably, the agent comprises an agent that overexpresses miR-194-3 p.
Preferably, the agent that overexpresses miR-194-3p comprises a miR-194-3 p-overexpressing vector or a miR-194-3 p-overexpressing mimetic or miR-194-3 p-overexpressing exosome.
The invention also provides application of the reagent for detecting miR-194-3p in preparation of a diabetic cardiomyopathy diagnostic product.
The invention provides application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy. miR-194-3p can be used as a potential drug target for treating diabetic myocardial fibrosis. The miR-194-3p overexpression can obviously improve the left ventricular diastolic function of a diabetic mouse and myocardial fibrosis of the mouse, and obviously reduce the fibrosis area. And by detecting the expression quantity of miR-194-3p, the early diagnosis of the diabetic cardiomyopathy can be realized.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions of the prior art, the drawings that are needed in the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a flow chart of the overall experiment of the invention provided by the invention;
FIG. 2 is a graph of modeling and evaluation results of an animal model provided by the invention; wherein: (a) a body weight curve (B) a blood glucose curve (C) a cholesterol curve (D) a triglyceride curve (E) a glucose tolerance test GTT (F) insulin resistance results plot;
FIG. 3 is a graph showing the results of extraction, identification and fibroblast uptake of cardiac muscle exosomes provided by the invention; wherein, (A) the result graph of detecting the myocardial cell exosome form by using a myocardial cell exosome electron microscope; (B) a representative map of NTA detection of myocardial extracellular fluid; (C) a myocardial extracellular secretion-associated NTA statistic; (D) A myocardial extracellular secretion related marker WB detection result diagram;
FIG. 4 is a graph showing the results of inhibiting vesicle secretion in a diabetic mouse; wherein (A) E/E' results of Doppler ultrasound suggest a left ventricular diastolic function result map; (B) A result chart of the reduction of the weight-to-heart ratio of the sirius red dyeing prompt; (C) Fibrosis staining suggests a decrease in interstitial fibrosis area; (D) A graph of results of expression of the associated fibrotic markers Col1, col1a1, a-SMA; (E) The immunofluorescence image prompts muscle fiber to obtain a result image of obvious reduction of the expression quantity of the marker a-SMA; (F) qPCR detection of Col1, col1a1, a-SMA expression profile for the relevant fibrotic markers;
fig. 5 is a graph of the result of analyzing differential exosome miR by the chip provided by the invention; wherein, (A) differential miR (B) human-mouse homologous miR thermogram; (C) qPCR detection of human and mouse homologous pri-miR result diagram; (D) qPCR analysis of a graph of the expression result of related mature miR of myocardial exosomes in a high-fat and high-sugar state; (E) qPCR analysis of miR-194 family expression results in myocardial cells, fibroblasts and myocardial exosomes; (F) qPCR analysis shows the expression result of miR-194-3p of fibroblast after adding high-fat and high-sugar myocardial exosomes; (G) After injecting the same number of cardiac muscle cell secreted exosomes into HFD mice, the expression result graph of miR-194-3p in serum exosomes;
FIG. 6 is a graph showing the result of the reversion of miR-194-2 agoniR in diabetic mice; wherein, (A) an E/E' result plot of Doppler ultrasound; (B) sirius red staining and a weight-to-weight ratio result graph; (C) a interstitial fibrosis outcome map; (D) WB results plot of qPCR (E) related fibrosis Marker and TGFb signal pathway of related fibrosis Marker; (F) Myocardial tissue immunofluorescence shows a graph of the results of the increased expression of a-SMA in the high-fat and high-sugar myocardial exosome injection group;
FIG. 7 is a graph of the results of actions in clinical specimens provided by the present invention; wherein, (A) a serum exosome electron microscope detection result diagram; (B) serum exosome NTA outcome profile; (C) a statistical graph of serum exosome NTA; (D) WB results for serum exosomes associated markers; (E) An expression result diagram of miR-194-3p in serum exosomes of clinical samples; (F) Expression result diagram of specific CD172a+ exosome miR-194-3p of serum exosome central muscle of clinical sample; (G) A graph of the results of the expression of a-SMA after the serum exosomes of the DM patients are added to the fibroblasts; (H) Results of morphological observation of fibroblasts (conversion to myofibroblasts) after addition of serum exosomes to fibroblasts in DM patients; (I) A result chart of the expression condition of the related marker after the serum exosomes of the DM patient are added into the fibroblasts; (J) qPCR results of related markers after serum exosomes of DM patients are added to fibroblasts;
fig. 8 is a development mechanism diagram provided by the present invention.
Detailed Description
The invention provides application of miR-194-3p in preparation of a medicament for treating diabetic cardiomyopathy. In the invention, the nucleotide sequence of miR-194-3p is shown in SEQ ID NO. 1: GUGGCUCCCACCCUCUGUAACAGCAACUCCAUGUGGAAGUGCCCACUG GUUCCAGUGGGGCUGCUGUUAUCUGGGGUGGCGGCUAG. FIG. 8 is a diagram of the development mechanism of a scheme for preparing a medicament for treating diabetic cardiomyopathy by utilizing miR-194-3 p. As shown in FIG. 8, miR-194-3p secreted by cardiomyocytes binds to TGF-beta receptor on the surface of fibroblasts, enters into fibroblasts, binds to TGF-beta R receptor in TGF-smad signaling pathway, and inhibits TGF-smad signaling pathway expression. Under the condition of diabetes, the expression quantity of miR-194-3p is obviously reduced, and the capability of inhibiting the TGF beta-smad signal channel is weakened, so that the TGF beta-smad signal channel is up-regulated to promote myocardial fibrosis. According to the invention, the exogenous miR-194-3p is supplemented, so that the TGF beta-smad signal channel expression in the heart fibroblast is reduced, and the myocardial fibrosis formation in a diabetes state is reduced.
The invention also provides application of miR-194-3p in preparation of a medicament for treating diabetic myocardial fibrosis.
The invention also provides application of miR-194-3p in preparation of a medicament for improving diabetic left ventricular diastolic dysfunction.
In the present invention, the drug preferably comprises an agent that overexpresses miR-194-3 p. In the present invention, the agent for over-expressing miR-194-3p comprises a carrier for over-expressing miR-194-3p or a mimic for over-expressing miR-194-3p (miR-194-3 pagomiR) or an exosome for over-expressing miR-194-3 p.
The invention discovers that miR-194-3p in myocardial exosomes derived from myocardial cells can be used as a potential drug target for treating diabetic myocardial fibrosis. The miR-194-3p overexpression can obviously improve the left ventricular diastolic function of a diabetic mouse and myocardial fibrosis of the mouse. The miR-194-3p expression in the heart and serum is obviously increased, especially the expression of the serum central myocyte derived exosome miR-194-3p is obviously increased, and the left ventricular diastolic function and myocardial fibrosis are obviously improved.
Specifically, the invention examines the reversion effect of the myocardial exosome miR-194-3p on the heart function and the diabetic myocardial fibrosis of a diabetic mouse through the over-expression miR-194-3pago miR-194-3p of the tail vein injection, and discovers that the myocardial exosome miR-193-3p mimic can obviously improve the left ventricular diastolic function and the myocardial fibrosis of the diabetic mouse.
The invention also provides application of miR-194-3p in preparation of a medicament for reducing the myocardial fibrosis area of diabetes. According to the invention, the expression of miR-194-3p in specific exosomes secreted by blood central myocytes is used for evaluating the myocardial fibrosis area of diabetes mellitus, and the miR-194-3p can obviously reduce the fibrosis area; the expression of miR-194-3p in specific exosomes secreted by myocardial cells was evaluated by animal models to be strongly inversely correlated with the area of diabetic myocardial fibrosis.
In the invention, the over-expression mode of miR-194-3p is not particularly limited, a conventional over-expression vector can be constructed for implementation, an exosome for over-expressing miR-194-3p can be constructed, and over-expression mimics of miR-194-3p, such as miR-194-3p agoniR, purchased from Ruibo organisms and provided with the product number miR40017148-4-5 or miR40004671-4-5, can be directly purchased.
The invention also provides application of the reagent for detecting miR-194-3p in preparation of a diabetic cardiomyopathy diagnostic product. The reagent for detecting miR-194-3p is not particularly limited, and can be a miR-194-3p detection kit, and the kit is from Thermo Fisher with the following product number: 002379. in the case of diabetes, the present invention found that miR-193-3p expression was significantly reduced relative to normal. The diagnosis of the diabetic cardiomyopathy can be realized by detecting the expression quantity of miR-193-3 p.
For further explanation of the present invention, the application of miR-194-3p provided by the present invention in preparing a medicament for treating diabetic cardiomyopathy is described in detail below with reference to the accompanying drawings and examples, but they are not to be construed as limiting the scope of the present invention.
Example 1
Diabetes mouse model evaluation
Diabetic mice were modeled by high fat diet and STZ injection. The flow chart is shown in figure 1.
Mice body weight was measured every month and blood glucose, cholesterol and triglycerides were detected by tail vein collection. Specifically, blood glucose levels were measured by venous blood collection at 0min,15min,30min,60min, and 120min, respectively. A body weight curve (a in fig. 2), a blood glucose curve (B in fig. 2), a cholesterol curve (C in fig. 2), and a triglyceride curve (D in fig. 2) were prepared, respectively. Diabetic mice modeling was evaluated by a glucose tolerance test (E in fig. 2) and an insulin tolerance test (F in fig. 2). The evaluation result of the animal model shows that the model of the mice (HFD for short) in the invention accords with the insulin resistance model of the diabetes mice.
Myocardial cell and serum exosome separation evaluation experiment
Exosome evaluation experiment of Normal myocardial cell secretion
The exosome group secreted by the normal cultured myocardial cells and the exosome group secreted by the high-fat high-sugar cultured myocardial cells are successfully purified by combining an ultracentrifugation method and a filtration method. First, the size and shape of the exosomes secreted by normal cardiomyocytes were observed by electron microscopy negative staining, and the purified exosomes were found to be round, well-defined, mostly less than 100nm (a in fig. 3). The distribution of the extracted exosomes secreted by normal cardiomyocytes was shown by a nanoparticle analyzer with a diameter mean of 86.9nm (B in fig. 3), conforming to the exosome size. The statistics by the nanoparticle analyzer show that the number of cardiac myocytes secreting exosomes is significantly increased in the high-fat high-sugar (HGHL) state compared to the normal culture group (NG/NL) (C in fig. 3). The Westernblot results suggest that the marker proteins CD63, CD81, alix and TSG101 of the exosomes are enriched in normal culture exosome components (D in fig. 3). Prompting the extraction method and concentration of exosomes to meet the requirements of subsequent experiments.
The same number 1 x 10 6 Evaluation experiments of cardiac function of mice with diabetes were injected with normal culture cardiac exosomes (N-EV) and high-fat high-sugar culture cardiac exosomes (H-EV), respectively.
The effect of high-fat high-sugar myocardial exosomes on diabetic mouse myocardial fibrosis was judged by doppler echocardiography (a in fig. 4) and sirius scarlet staining (B in fig. 4 and C in fig. 4). The high-fat and high-sugar myocardial exosomes decrease the left ventricular diastolic function and increase the myocardial fibrosis area of diabetic mice. The immunofluorescence of myocardial tissue shows that the expression of a-SMA in the high-fat and high-sugar myocardial exosome injection group (E in fig. 4) is increased, and the expression level of the related marker of myocardial fibrosis is obviously increased, which indicates that the expression level of the related molecule of myocardial fibrosis is obviously increased. Cardiac tissue detection of fibrosis-associated molecular markers by WB: expression of a-SMA, col1 and col1A1 in diabetic mouse myocardium found that the tissue injected with high-fat high-sugar myocardial exosomes, the expression of the fibrosis molecules was significantly increased (D in fig. 4), and expression of fibrosis-related markers a-SMA, col1 and col1A1 in diabetic mouse myocardium was detected by qPCR, and the expression of the fibrosis molecules was significantly increased (F in fig. 4). The experiment shows that the high-fat and high-sugar myocardial exosome weight-added diabetic mice have myocardial fibrosis.
Chip analysis of differential microRNA
By using an miRNA chip array strategy, 38 different exosomes miRNAs are identified from exosomes secreted by the myocardial cells cultured by high fat and high sugar compared with a normal group, 11 human-mouse homologous miRNAs are found by database comparison, the expression of the human-mouse homologous differential miRNAs in myocardial cells EV in different states is verified by qPCR analysis, and the target genes and biological functions of the target miR-194-3p are predicted by bioinformatics analysis.
Specifically, the differential exosome miRNA secreted by normal and high-fat high-sugar cultured myocardial cells is analyzed by a miRNA chip. Obtaining 38 differential miRNA volcanic charts (A in figure 5), analyzing differential miR, analyzing human and mouse homologous differential miR results are shown as B in figure 5, verifying the expression of pri-miR and mature miR through qPCR (C-E in figure 5), wherein after qPCR analysis is carried out on myocardial exosomes cultured by normal and high-fat and high-sugar, the expression of miR-194-3p of fibroblasts is obviously reduced (F in figure 5, NG/NL is normal culture, HG/HL is high-fat and high-sugar culture), and after the same number of exosomes secreted by myocardial cells cultured by normal culture and high-fat and high-sugar culture are respectively injected into diabetic mice, the expression of miR-194-3p in serum exosomes of an exosomes injection group (G in figure 5) of the myocardial cells cultured by high-fat and high-sugar culture is obviously reduced.
Reverse action of miR-194-3 overexpression in diabetic mice
The effect on cardiac function and cardiac fibrosis, i.e., the regulation of miR-194-3p on cardiac fibrosis, was evaluated by injecting diabetic mice with an expressed miR-194-3p mimetic (miR-194-3 p agoniR (agoniR-194-3 p), purchased from Ruibo organisms, under the product number miR40017148-4-5, in an injection amount of 10nmol of miR-194-3p agoniR per mouse. The E/E' of Doppler ultrasound showed left ventricular diastolic function (A in FIG. 6), suggesting that expressing miR-194-3p has a significant effect on improving left ventricular diastolic function. Sirius scarlet staining showed a heart weight ratio (B in fig. 6) in diabetic mice, showing significant differences in over-expression of miR-194-3p for improving heart weight ratio. The area of interstitial fibrosis (C in FIG. 6) shows that the over-expression of miR-194-3p is significantly smaller for the area of interstitial fibrosis. Detection of the relevant fibrosis markers and tgfβ signaling pathway-related molecules by WB and qPCR, respectively, showed a significant decrease in cardiac fibrosis-related molecular marker expression (D in fig. 6 and E in fig. 6), with significant downregulation of Col1, col1A1 and α -SMA expression. The expression of miR-194-3p by heart tissue through fibrotic alpha-SMA (F in FIG. 6) suggests that expression of miR-194-3p is significantly reduced for improving heart fibrosis. Through the experiment, the miR-194-3p is over-expressed, and has obvious effects on improving the left ventricular diastolic function and myocardial fibrosis of the heart.
Example 2
Serum sources and extraction
Patient diagnosis and inclusion criteria according to embodiments of the present invention: the invention meets the requirements of medical ethics and ethics committee of Beijing An Zhen hospital affiliated to the university of capital medical science and obtains the informed consent of patients. All experimental participants were sourced from the endocrinology department and physical examination center of the Beijing An Zhen hospital. In order to reduce the hybridization of samples and reduce the interference of other diseases on experimental data, the invention strictly eliminates diseases such as hypertension, dyslipidemia, tumor, psychoneurosis and the like, and performs strict gender and age pairing among groups, and the specific requirements are shown in table 1.
Table 1 clinical and biochemical characteristics of subjects participating in the study
Note that: the above values are expressed as mean ± standard deviation.
Blood is preferably morning blood. The subjects fasted prior to morning blood collection. Blood samples were collected in tubes and serum was collected by centrifugation as soon as possible. The exosomes can be stored more stably in serum at 4 ℃, -20 ℃, -40 ℃ or-80 ℃. All of the above experimental enrolled participants were between 27 and 75 years old. Each group of samples needs to be taken to be 5mL (without anticoagulant serum tube collection), and after centrifugation at 2000g for 10min, serum is separated into a 1.5mL centrifuge tube, and centrifugation at 2000g for 10min is performed again to further remove blood cell sediment in the centrifuge tube, so that serum is obtained.
Serum exosome extraction
Taking 2mL of morning blood serum, diluting with PBS in equal amount, centrifuging at 4 ℃ for 30min at 2,000Xg, discarding cell sediment, collecting supernatant, centrifuging at 12,000Xg at 4 ℃ for 45min, further discarding impurity sediment such as cell debris, centrifuging at 110,000Xg in a Backman (USA) ultracentrifuge at 4 ℃ for 2h, and obtaining sediment, namely a primary extract of serum exosomes. To further purify the exosomes, the serum exosome primary extract was resuspended in 1ml pbs, filtered through a 0.22 μm filter and centrifuged at 110,000×g for 70min at 4 ℃, the pellet was washed with 1ml pbs resuspension, centrifuged at 110,000×g at 4 ℃ for 70min, and the pellet was the purified serum exosomes. Through the above centrifugation, filtration and two washes of PBS, cell debris outside the exosomes, other extracellular vesicles, and other serum proteins adhering to the exosomes can be removed.
Method for detecting external secretion experience
Negative-dyeing photograph of electron microscope
After serum ultracentrifugation and filtration to obtain serum exosomes, the purity and concentration of serum exosomes are determined. The size and shape of serum exosomes were first observed by electron microscopy negative staining. After resuspension of serum exosomes with PBS, exosomes were transferred onto a carbon-supported film covered copper mesh and stained with an equal volume of 2% uranyl acetate for 60 seconds. Thereafter, the copper mesh was observed for the size and integrity of human serum exosomes under a FEITecnai20 electron microscope.
The size and shape of the normal human exosomes were observed by electron microscopy negative staining, and the purified exosomes were found to be round, well-defined, less than 100nm (a in fig. 7).
Western blotting detection
Serum exosomes, whole serum and serum from which exosomes were removed were dissolved in RIPA buffer (25 mM Tris-HCl ph7.6,150mM NaCl,1% np-40,1% sodium deoxycholate, and 0.1% SDS), and 5 x SDS loading buffer was added, denatured at 95 ℃ for 5min, subjected to SDS-PAGE electrophoresis and transfer, and after blocking with 5% skim milk, primary antibodies against CD63 and CD81 (both from SBI) were diluted with primary anti-diluent 1:1000, hybridized overnight at 4 ℃ and horseradish peroxidase-conjugated secondary antibodies were incubated at room temperature for 2h, and ECL color reaction was performed. Protein SDS-PAGE gel silver staining is used as an internal reference of protein loading. The enrichment of human serum exosomes samples with the marker proteins CD63 and CD81 was examined in this way. Western blot results suggest that the marker proteins CD63 and CD81 of the exosomes are enriched in the exosome components (D in FIG. 7).
Serum exosome concentration determination
The distribution of extracted human serum exosomes was detected by nanoparticle analyzer Delsa Nano C particle analyzer (Beckman-Coulter); nanoSight NS300 (Malvern Instruments, UK) detects serum exosome concentrations.
Panel B in FIG. 7 shows the distribution of extracted serum exosomes by nanoparticle analysis, diameter mean 86.9nm. It is proved that the exosomes in the human serum extracted by the ultracentrifugation method are fully satisfactory.
FIG. 7C shows that serum exosome concentrations were measured using NanoSight NS300, and the results showed that diabetic patients (32.72.+ -. 1.45e+11 particles/mL) were significantly increased compared to normal persons (10.25.+ -. 2.48e+11 particles/mL). Indicating that the secretion of exosomes in the blood of patients is also significantly increased in the diabetic state.
The above experiment confirms that the exosome extraction purity is high, and the next analysis experiment can be performed.
Clinical samples of endocrinology department and physical examination center of An Zhen hospital are selected for separation and extraction of exosomes, miR-194-3p detection is carried out through qPCR (E in fig. 7), and the result indicates that the expression of miR-194-3p of diabetics is obviously down-regulated. The detection of the expression of miR-194-3p in the specific myocardial exosomes secreted by the myocytes in the serum samples (F in FIG. 7) indicated that the expression of miR-194-3p was significantly down-regulated in diabetic patients. The invention has guiding significance for clinic, namely, can provide reference for a new molecular diagnosis and evaluation method of the diabetic myocardial fibrosis, and prompts the diagnosis of the diabetic myocardial fibrosis by judging the concentration of the exosome miR-194-3p in the serum of a patient. Better help the clinician evaluate and judge the myocardial fibrosis caused by diabetes. Expression of a-SMA following addition of serum exosomes from patients with DM to fibroblasts (G in fig. 7) shows that exosomes in serum from diabetics can promote expression of myofibroblast markers. Morphological observation of fibroblasts after addition of serum exosomes from DM patients (H in fig. 7) showed that serum exosomes from diabetics can promote the expression of myofibroblast markers. Expression of related molecular markers qPCR after addition of serum exosomes from diabetics to fibroblasts (J in fig. 7), a summary of the whole invention is shown in fig. 8. The western results of the fibroblast molecular markers (I in fig. 7) after adding serum exosomes from DM patients to fibroblasts showed that exosomes in serum from diabetics could promote expression of the fibroblast molecular markers. The results indicate that exosomes in diabetic human blood can promote the transformation of cardiac fibroblasts into myofibroblasts, exacerbating myocardial fibrosis.
Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (7)
- Application of miR-194-3p in preparation of medicine for treating diabetic cardiomyopathy.
- Application of miR-194-3p in preparation of medicine for treating diabetic myocardial fibrosis.
- Application of miR-194-3p in preparation of medicine for improving diabetic left ventricular diastolic dysfunction.
- Application of miR-194-3p in preparation of medicine for reducing diabetic myocardial fibrosis area.
- 5. The use of any one of claims 1 to 4, wherein the medicament comprises an agent that overexpresses miR-194-3 p.
- 6. The use of claim 5, wherein the agent that overexpresses miR-194-3p comprises a miR-194-3 p-overexpressing vector or a miR-194-3 p-overexpressing mimetic or a miR-194-3 p-overexpressing exosome.
- 7. Application of reagent for detecting miR-194-3p in preparation of diabetic cardiomyopathy diagnosis product.
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