CN103285406B - MicroRNA-203, and application of analogue thereof in preparation of medicament for preventing and treating obesity, dyslipidemia and complication of obesity and dyslipidemia - Google Patents
MicroRNA-203, and application of analogue thereof in preparation of medicament for preventing and treating obesity, dyslipidemia and complication of obesity and dyslipidemia Download PDFInfo
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- CN103285406B CN103285406B CN201310201199.XA CN201310201199A CN103285406B CN 103285406 B CN103285406 B CN 103285406B CN 201310201199 A CN201310201199 A CN 201310201199A CN 103285406 B CN103285406 B CN 103285406B
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Abstract
The invention discloses microRNA-203, and application of an analogue of the microRNA-203 in preparation of a medicament for preventing and treating obesity, dyslipidemia and complication of the obesity and the dyslipidemia and belongs to the field of biological medicine. The prepared medicament disclosed by the invention can be miR-203 and a single ingredient of the analogue of the miR-203, and also can be a pharmaceutical composition. The pharmaceutical composition is prepared from effective dosage of miR-203 and/or analogue thereof and a pharmaceutical acceptable carrier in a mixing manner; the carrier can be cholesterol, virus, nano-particles, chitosan, lipidosome and the like; synthetic miR-203 and/or the analogue thereof are/is connected with the carrier to form the medicament. The medicament can be used for treating the obesity, the dyslipidemia or the complication of the obesity and the dyslipidemia by vein, muscle or intraperitoneal injection and the like.
Description
Technical field
The present invention relates to a kind of nucleic acid material and prepare the application in prevention and therapy disease medicament, particularly relate to microRNA-203(miR-203) and to intend like thing, preparing the application in prevention and therapy obesity, dyslipidemia and fat and dyslipidemia complication medicine, the invention belongs to biomedicine field.
Background technology
Obesity is a kind of by the multifactor chronic metabolic disease caused, and has obvious relation, be called as in " sources of ten thousand diseases " with various diseases such as diabetes, hypertension, hyperlipemia, cardiovascular and cerebrovascular disease and cancers.At present, obesity has been listed as the world four and has lived greatly a difficult problem with acquired immune deficiency syndrome (AIDS), drug and alcohol abuse, is acknowledged as one of important pertinacious disease of puzzlement human health.According to the data display that " International Obesity problem working group " announces, the earth just there is 1 people to be too obese in every 4 people.Specifically, the whole world 3.12 hundred million body weight for humans exceed standard, and 1,700,000,000 people should lose weight.Report is pointed out, whole world population of being obese has exceeded hungry population, and Overweight and obesity has become a Social Events of puzzlement developed country and developing country, is also the huge challenge that whole human society will face.
Fat can with or without the generation of dyslipidemia, dyslipidemia is a kind of systemic disease, to refer in blood T-CHOL (TC) and/or triglyceride (TG) is too high or HDL-C (HDL-C) is too low, also claim hyperlipemia.The main harm of hyperlipemia causes atherosclerosis, and then cause numerous relevant diseases, and wherein modal a kind of fatal disease is exactly coronary heart disease, and serious chylomicronemia can cause acute pancreatitis, is another fatal disease.In addition, hyperlipidemia is also the important risk factor causing hypertension, impaired glucose tolerance, diabetes.Hyperlipemia also can cause fatty liver, liver cirrhosis, cholelithiasis, pancreatitis, retinal hemorrhage, blind, peripheral vascular disease, limping, hyperuricemia.
At present, unsatisfactory for prevention effect that is fat and dyslipidemia, very easily cause the generation of multiple complications, be therefore badly in need of setting up a kind of active drug researched and developed with new therapy target.MicroRNA(miRNA) be the micromolecule non-coding single stranded RNA that a class length is about 22nt, processed by the single stranded RNA precursor of about 70-90 the base size with hairpin structure, can combine with 3 ' end untranslated region of the said target mrna of complementary or partial complementarity, make mRNA degrade or mediate its Translational repression.The member of miRNA family is as the of short duration RNA(stRNA of micromolecule in the growth transition process of research C. Elegans Automatic Screening) be found.Research finds, miRNA is extended familys in stRNA, and is all found in nematicide, fruit bat, plant, mammal, even virus.This kind of tiny RNA has the specificity of tissue and time on expressing, it is the important Molecular regulator regulating other functional genes to express, research shows, the regulation and control of the processes such as miRNA wide participation growth, apoptosis, differentiation, propagation, metabolism, play an important role in the various vital movements of organism.In recent years, the medicine being target spot based on miRNA constantly obtains Success in Experiment, thus brings new hope for the treatment of various disease, and therefore, the novel targets of fat as treatment using miRNA of dyslipidemia, has very great breakthrough and application.
Summary of the invention
In order to solve the problem, the present invention adopts multiple technologies means to demonstrate microRNA-203(miR-203) or its to intend like thing at the expression suffered from obesity individuality and to preventive and therapeutic effect that is fat and dyslipidemia, finally determine miR-203 or it is intended like thing can as preparation prevention or treatment be fat, dyslipidemia and active drug that is fat and dyslipidemia complication.
Therefore, the present invention proposes microRNA-203 or the seemingly application of thing in preparation prevention or treatment obesity, dyslipidemia or obesity and dyslipidemia complication medicine of its plan,
Wherein, described microRNA-203 sequence is as shown in SEQ ID NO.1; Described plan like the sequence of thing as shown in SEQ ID NO.2 or SEQ ID NO.3.
In the present invention, preferably, described obesity and dyslipidemia complication comprise atherosclerosis, coronary heart disease, myocardial hypertrophy, pancreatitis and fatty liver.
Certainly; those skilled in the art can intend suitably modifying like the nucleotide sequence of thing to microRNA-203 of the present invention or its; described modification comprises that the ribose of any nucleotide is modified, base modification and phosphate backbones modify in the combination of one or more or the increase and decrease of nucleotide arbitrarily, replacement, just should belong within invention which is intended to be protected as long as the nucleotide sequence after modifying still has the activity identical with microRNA-203.
The plan of a kind of microRNA-203 of the present invention, like thing, is characterized in that the sequence of described plan like thing is as shown in SEQ ID NO.2 or SEQ ID NO.3.
In addition, the invention allows for a kind of for prevention or treatment is fat, dyslipidemia and dyslipidemia complication pharmaceutical composition, it is characterized in that plan containing above-described microRNA-203 seemingly thing and the carrier that pharmaceutically accepts.
In the present invention, preferably, also microRNA-203 is comprised in described pharmaceutical composition.
In the present invention, preferably, described carrier is virus, cholesterol, nano-particle, chitosan or liposome.
In the present invention, preferably, the conventional method that described compositions is prepared according to medicine can be made ejection preparation, oral formulations, spray agent, ointment formulation or patch etc.
Accompanying drawing explanation
Fig. 1 is each group of rat 4 weeks body weight change situations;
Fig. 2 respectively organizes TG content in rat blood serum 4 weekends;
Fig. 3 respectively organizes TCH content in rat blood serum 4 weekends;
Fig. 4 respectively organizes LDL content in rat blood serum 4 weekends;
Fig. 5 respectively organizes HDL content in rat blood serum 4 weekends.
Detailed description of the invention
Below by pharmacological and clinical observation experiment and the present invention is described further checking in conjunction with the embodiments, all embodiments only for illustration the present invention, never limit the scope of the invention.
Embodiment 1miR-203, miR-203 intend intending like thing 2 therapeutical effect that is fat and dyslipidemia like thing 1, miR-203
Select body weight 160-165g adult healthy SD male rat, be divided into 6 groups: (1) Normal group (NC); (2) high lipid food brings out fat group; (3) high lipid food brings out shown in fat group injection miR-203(SEQ ID NO.1), injected dose is 0.1ml/0.5nmol; (4) high lipid food brings out fat group injection miR-203 plan like shown in thing 1(SEQ ID NO.2), injected dose is 0.1ml/0.5nmol; (5) high lipid food brings out fat group injection miR-203 plan like shown in thing 2(SEQ ID NO.3), injected dose is 0.1ml/0.5nmol; (6) high lipid food brings out fat group injection negative control reagent, negative control reagent main component is cel-miR-239b-5p, cel-miR-67-3p, this miRNA and anyone, rat, mice miRNA is almost without homology, be widely used in miRNA related experiment, injected dose is 0.1ml/0.5nmol(negative control group).3,4,5,6 groups of rat laparotomies, through injection into mesentery reagent, respectively organize under rat is in equivalent state with other after sewing up and raise 35 days, and every 7 days weighing fasting body weight, within 35 days, drew materials in end, gets serum.
Each group of body weight change as shown in Figure 1.Result visible miR-203, miR-203 intend intending being starkly lower than Obesity group (P<0.05), close to the matched group that normal diet brings out like thing 2 effect group rat body weight like thing 1, miR-203.Respectively organize TG, TCH, LDL, HDL content in rat blood serum with kits, as shown in Figure 2-5, matched group relatively fat group TG, TCH, LDL significantly reduce (P<0.05) result, and HDL content significantly raises (P<0.05); MiR-203 group TG, TCH, LDL content is all remarkable in Obesity group (P<0.05), and it is close with matched group content that HDL content is significantly higher than fat group (P<0.05), NC group then with obesity group without significant difference.
This experiment demonstrates miR-203, and miR-203 intends seemingly thing 1, miR-203 and intends can significantly improving obesity and dyslipidemia like injection in thing 2 body, illustrates that miR-203 can be used as the novel drugs of prevention and therapy obesity and dyslipidemia.
The above is illustrative embodiment of the present invention, and nonrestrictive, changes, all fall within protection scope of the present invention for the change done in the claims in the present invention or equivalence.
Claims (6)
1.microRNA-203 or its plan are preparing like thing the application preventing or treat in obesity or dyslipidemia medicine,
Wherein, the sequence of described microRNA-203 is as shown in SEQ ID NO.1; Described plan like the sequence of thing as shown in SEQ ID NO.2 or SEQ ID NO.3.
2. the plan of microRNA-203 is like a thing, it is characterized in that the sequence of described plan like thing is as shown in SEQ IDNO.2 or SEQ ID NO.3.
3., for preventing or treat a pharmaceutical composition for obesity, dyslipidemia, it is characterized in that plan containing microRNA-203 according to claim 2 is like thing and the carrier that pharmaceutically accepts.
4. pharmaceutical composition as claimed in claim 3, characterized by further comprising microRNA-203, the sequence of described microRNA-203 is as shown in SEQ ID NO.1.
5. pharmaceutical composition as claimed in claim 3, is characterized in that described carrier is virus, cholesterol, nano-particle, chitosan or liposome.
6. the pharmaceutical composition as described in any one of right 3-5, is characterized in that the conventional method by described compositions is prepared according to medicine makes ejection preparation, oral formulations, spray agent, ointment formulation or patch.
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| CN201310201199.XA CN103285406B (en) | 2013-05-27 | 2013-05-27 | 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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| CN103961719B (en) * | 2014-03-14 | 2018-01-23 | 牡丹江医学院 | 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102943108A (en) * | 2006-01-05 | 2013-02-27 | 俄亥俄州立大学研究基金会 | Microrna-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102943108A (en) * | 2006-01-05 | 2013-02-27 | 俄亥俄州立大学研究基金会 | Microrna-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer |
Non-Patent Citations (2)
| Title |
|---|
| miR一203受到CEBPB及TCF4调控并通过靶向抑制survivin,AKT2,NP63表达来促进细胞分化;陈雪丹等;《2011中国遗传学会大会论文摘要汇编》;20111231;138 * |
| 季晨博等.miRNA与脂肪细胞分化、肥胖.《中国儿童保健杂志》.2012,第20卷(第5期),419-423. * |
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