CN103961719B - The application of microRNA 23b and its plan like thing in the medicine for preparing preventing and treating obesity, high fat of blood, hypertension and its complication - Google Patents
The application of microRNA 23b and its plan like thing in the medicine for preparing preventing and treating obesity, high fat of blood, hypertension and its complication Download PDFInfo
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- CN103961719B CN103961719B CN201410097269.6A CN201410097269A CN103961719B CN 103961719 B CN103961719 B CN 103961719B CN 201410097269 A CN201410097269 A CN 201410097269A CN 103961719 B CN103961719 B CN 103961719B
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Abstract
The present invention relates to the application of microRNA 23b and its plan like thing in the medicine for preparing preventing and treating obesity, high fat of blood, hypertension and its complication, described microRNA 23b nucleotide sequence is as shown in SEQ ID NO.1；The microRNA 23b intend being classified as on the basis of microRNA 23b nucleotide sequence like the nucleotides sequence of thing, ribose modification, base modification and the one or more of combinations or the increase and decrease of nucleotides, replacement in phosphate backbones modification carried out to other nucleotides in addition to UCACAUU bases.Medicine prepared by the present invention can be microRNA 23b and its intend private thing single component, or a kind of pharmaceutical composition.By vein, muscle or intraperitoneal injection etc. can be used to treat obesity, high fat of blood, hypertension and its complication medicine of the present invention.
Description
Technical field
The present invention relates to microRNA-23b and its intend like thing prepare preventing and treating obesity, high fat of blood, hypertension and its concurrently
Application in the medicine of disease, belongs to biomedicine field.
Background technology
Obesity is a kind of by multifactor caused chronic metabolic disease, with diabetes, hyperlipidemia, cardiovascular and cerebrovascular disease
And a variety of diseases such as cancer have obvious relation, it is referred to as in " sources of ten thousand diseases ".At present, it is fat with AIDS, drug and alcohol abuse
Four big problem concerning life of the world is listed as, is acknowledged as perplexing one of important chronic disease of human health.According to " International Obesity problem works
The data that group " is announced show just have 1 people to be too obese in every 4 people on the earth.Specifically, global 3.12 hundred million people's overweights,
1700000000 people should lose weight.Report points out that whole world population of being obese exceedes hungry population, and overweight and fat have become perplexs hair
Up to a Social Events of country and developing country, and the whole human society huge challenge to be faced.
Obesity can with or without high fat of blood generation, high fat of blood is a kind of systemic disease, refers to T-CHOL in blood
（TC）And/or triglycerides（TG）Too high or HDL-C（HDL-C）It is too low, also referred to as hyperlipidemia.Hyperlipemia
The main harm of disease is to cause atherosclerosis, and then causes numerous relevant diseases, a kind of mortality of most common of which
Disease is exactly coronary heart disease, and serious chylomicronemia can cause acute pancreatitis, is another fatal disease.In addition, high fat
Mass formed by blood stasis is also to cause IGT, an important risk factor of diabetes.It is hard that hyperlipidemia can also result in fatty liver, liver
Change, cholelithiasis, pancreatitis, fundus hemorrhage, peripheral vascular disease, hyperuricemia.
At present, it is unsatisfactory for fat and high fat of blood prevention effect, the generation of multiple complications is easily caused, therefore
It is badly in need of establishing a kind of active drug researched and developed with new therapy target.microRNA（miRNA）Transcribed originating from endogenous expression
This, is the double stranded rna molecule for being about 21-25nt.Ripe microRNA can combine gene silencing complex（RNA-
Induced Silencing Complex,RISC）It is and complementary side by side with target mRNA；MicroRNA and target sequence complementary journey
Degree determines that target gene mRNA is partly suppressed in translation skill or is broken completely.In plant, the seemingly main work of fracture
Make mode, and major way is then suppressed to translation skill in mammal.Research shows that microRNA wide participations are sent out
Educate, apoptosis, differentiation, the regulation and control of propagation, the process such as metabolism, played an important role in the various vital movements of life entity.Closely
Nian Lai, Success in Experiment is constantly obtained based on the medicine that microRNA is target spot, so as to bring new wish for the treatment of various illnesss
Hope therefore, there is very great breakthrough and application as the fat novel targets with high fat of blood for the treatment of with microRNA.
The content of the invention
In order to solve the above problems, the present invention demonstrates microRNA-23b using multiple technologies means（miR-23b）And
It intends the application in the medicine for preparing preventing and treating obesity, high fat of blood, hypertension and its complication like thing.Wherein, it is described
MicroRNA-23b nucleotide sequence is as shown in SEQ ID NO.1；The microRNA-23b intends the nucleotide sequence like thing
For on the basis of microRNA-23b nucleotide sequence, to be carried out to other nucleotides in addition to UCACAUU bases
Ribose modification, base modification and one or more of combinations or the increase and decrease of nucleotides, replacement in phosphate backbones modification.It is preferred that
, it is right on the basis of microRNA-23b nucleotide sequence that described microRNA-23b plans are classified as like the nucleotides sequence of thing
Base has carried out the modification that methylates, and 5 ' ends are marked using cholesterol.
Described obesity, high fat of blood, hypertension complication include diabetes hepatopathy, diabetic cardiomyopathy, diabetic nephropathy,
Atherosclerosis, coronary heart disease, myocardial hypertrophy, pancreatitis and fatty liver.
Those skilled in the art can be carried out to microRNA-23b of the present invention and its plan like the nucleotide sequence of thing
Appropriate modification, described modification include ribose modification, base modification and the phosphate backbones of any nucleotides in addition to UCACAUU sequences
The increase and decrease of one or more of combinations or any nucleotides in modification, replace, as long as the nucleotide sequence after modification still has
It should just belong to microRNA-23b identicals activity within invention which is intended to be protected.
Further, present invention additionally comprises the blood that microRNA-23b detects as the diagnosis of obesity, high fat of blood, hypertension
Clear biomarker（Mark）.
Further, it is used to prevent present invention also offers one kind or treats obesity, high fat of blood, hypertension and complication
Pharmaceutical composition, the plan that the composition contains microRNA-23b or microRNA-23b receives like thing and pharmaceutically
Carrier.Preferably, described carrier is virus, cholesterol, nano particle, chitosan or liposome.
In the present invention, ejection preparation can be made according to the conventional method of medicine preparation in above-mentioned composition, oral formulations,
Spray agent, ointment formulation or patch etc..
Brief description of the drawings
Fig. 1 is 1 month each group db/db trangenic mice body weight situation of change；
Fig. 2 is TG contents in each group db/db trangenic mice serum after 1 month；
Fig. 3 is TG contents in each group db/db trangenic mice livers after 1 month；
Fig. 4 is TG contents in each group db/db trangenic mice adipose tissues after 1 month；
Fig. 5 is each group db/db trangenic mice fat HE dyeing and F4/80 immunofluorescences after 1 month；
Fig. 6 is each group db/db trangenic mice livers HE dyeing and liver cell electron microscopic picture after 1 month；
Fig. 7 is each group db/db trangenic mice blood pressures after 1 month；
Fig. 8 is that the normal C57B6 mouse of each group inject blood pressure after microRNA-23b analogs after 1 month.
Embodiment
The invention will now be further described with reference to specific embodiments, advantages of the present invention and feature will be with description and
It is apparent.But embodiment is only exemplary, does not form any restrictions to the scope of the present invention.Those skilled in the art should
It should be appreciated that the details and form of technical solution of the present invention can be repaiied without departing from the spirit and scope of the invention
Change or replace, but these modifications and replacement are each fallen within protection scope of the present invention.
Embodiment 1microRNA-23b and its microRNA-23b intend making like treatment of the thing to obesity, high fat of blood, hypertension
With.
（1）It is 45-50g adult healthy db/db transgenosis type II diabetes obesity mices from body weight（Shanghai Si Laike is moved
Thing company）, it is divided into 4 groups：1. Normal group；2. db/db transgenosis type II diabetes obesity mices；3. db/db transgenosis II
The injection of patients with type Ⅰ DM obesity mice contains microRNA-23b sequences（Shown in SEQ ID NO.1）Reagent, injection dosage is
0.2ml/10nM;4. db/db transgenosis type II diabetes obesity mice inject negative control reagent, negative control reagent mainly into
It is divided into the reagent containing sequence shown in SEQ ID NO.2, injection dosage 0.2ml/10nM.
The microRNA with anyone, rat, mouse microRNA almost without homology, be widely used in microRNA correlations
In experiment, injection injection dosage is 0.2ml/10nM.3rd, the injection in every 3 days of 4,5 groups of Db/Db mouse once, is surveyed after one month
Blood pressure, draw materials, take serum.
（2）It is 25-30g adult healthy C57BL mouses from body weight（Shanghai Si Laike）, it is divided into 3 groups：1. normal control
Group；2. normal C57BL mouse injects microRNA-23b（Shown in SEQ ID NO.1）, injection dosage 0.2ml/10nM;3. just
Normal C57BL mouse injection negative control reagent, negative control reagent main component is injection dosage 0.2ml/10nM.
The microRNA with anyone, rat, mouse microRNA almost without homology, be widely used in microRNA correlations
In experiment, injection injection dosage is 0.2ml/10nM.
Each group changes of weight is as shown in Figure 1.As a result visible microRNA-23b effects group rat body weight is significantly lower than simple
Fat group（P<0.05,P<0.001）.With TG contents in kits each group rat blood serum, liver, fat, as a result such as Fig. 2-4
Shown microRNA-23b effects group rat significantly reduces with respect to fat group TG（P<0.05,P<0.001）, Fig. 5 visible fats are thin
Cell space product is obviously reduced（P<0.001）, the visible liver HE of Fig. 6, which dye visible microRNA-23b, substantially to reverse adipocyte to increase
It is more, and fat drips significantly reduce in liver cell, the visible microRNA-23b of Fig. 7 can reduce dbdb transgenic obese mice blood pressures（P
<0.05,P<0.001）, the visible microRNA-23b of Fig. 8 can reduce normal C57BL mouse blood pressure（P<0.001）.
This experiment, which demonstrates microRNA-23b internal injections, can significantly improve obesity, high fat of blood, hypertension, explanation
MicroRNA-23b can be as the novel drugs for preventing and treating obesity, high fat of blood, hypertension.
Claims (2)
1.microRNA-23b is in the medicine of high fat of blood, hypertension and its complication caused by preparing preventing and treating type ii diabetes
Using, it is characterised in that described microRNA-23b nucleotide sequence is as shown in SEQ ID NO.1, described complication
Including atherosclerosis, coronary heart disease, myocardial hypertrophy, pancreatitis and fatty liver.
2. application according to claim 1, it is characterised in that described microRNA-23b nucleotide sequence is as II
High fat of blood, the blood serum designated object of hypertension diagnosis detection caused by patients with type Ⅰ DM.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103285406A (en) * | 2013-05-27 | 2013-09-11 | 哈尔滨医科大学 | MicroRNA-203, and application of analogue thereof in preparation of medicament for preventing and treating obesity, dyslipidemia and complication of obesity and dyslipidemia |
| CN103372218A (en) * | 2012-04-19 | 2013-10-30 | 中国科学院上海生命科学研究院 | microRNA related to autoimmune disease and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103372218A (en) * | 2012-04-19 | 2013-10-30 | 中国科学院上海生命科学研究院 | microRNA related to autoimmune disease and application thereof |
| CN103285406A (en) * | 2013-05-27 | 2013-09-11 | 哈尔滨医科大学 | MicroRNA-203, and application of analogue thereof in preparation of medicament for preventing and treating obesity, dyslipidemia and complication of obesity and dyslipidemia |
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| Circulating miRNAs as potential marker for pulmonary hypertension;Wei C;《PLOS ONE》;20130523;1-9 * |
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