CN108619162A - The construction method of type 1 diabetes mouse responsible drinking model - Google Patents
The construction method of type 1 diabetes mouse responsible drinking model Download PDFInfo
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- 230000035622 drinking Effects 0.000 title claims abstract description 22
- 238000010276 construction Methods 0.000 title claims abstract description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 title abstract description 8
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims abstract description 12
- 238000003304 gavage Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 6
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229960001052 streptozocin Drugs 0.000 claims abstract description 5
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 claims abstract description 4
- 210000004369 blood Anatomy 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 210000004923 pancreatic tissue Anatomy 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 26
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 10
- 238000010172 mouse model Methods 0.000 abstract description 6
- 241000699670 Mus sp. Species 0.000 abstract description 5
- 238000002474 experimental method Methods 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000013118 diabetic mouse model Methods 0.000 abstract description 3
- 239000007928 intraperitoneal injection Substances 0.000 abstract description 2
- 238000004088 simulation Methods 0.000 abstract description 2
- 244000309464 bull Species 0.000 abstract 1
- 230000002124 endocrine Effects 0.000 abstract 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 17
- 238000010171 animal model Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000011697 diabetes animal model Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000020097 white wine Nutrition 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
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- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention discloses the construction methods of type 1 diabetes mouse responsible drinking model, belong to medical animal experiment method；It is intended to drink model by establishing diabetic mice, drinks and certain basic data is provided for type 1 diabetes and science health.Method is to establish diabetic mouse model by low dose of repeatedly intraperitoneal injection streptozotocin after selecting bull C57BL/6J mouse, gavage to drink.The present invention has preferable stability and repeatability, and foundation is drunk and on the basis of type 1 diabetes mouse model, simulation diabetes patient drinks and detects corresponding endocrine indexes stablizing.
Description
Technical field
The present invention relates to a kind of medical assessment, detection methods, relate generally to a kind of application medical experiment animal methods.
Background technology：It is the indispensable a part of culture of human lives, social development to drink.It drinks and healthy relationship
Research, is also receiving more and more attention and is paying attention to.It is quite bright to digestion, the influence of internal system if it is improper to drink
It is aobvious.But responsible drinking is then different.In terms of angiocarpy, the blood pressure level less alcohol user and abstainer of responsible drinking person
It is low.Also some researches show that Mutation of Patients with Cardiomyopathy after excessive consumption of alcohol is changed to responsible drinking, and heart function is got back recovery.Pass through certain white wine
To being observed after intragastric administration on mice, the white wine in range of doses can be such that the oxidation resistance of mouse enhances.How E-at pleasure, drink with measure
It is particularly important.
Diabetes are a worldwide health problems, wherein type 1 diabetes (type 1diabetes
Mellitus, T1DM) clinical symptoms are more serious and involve young man more, and illness rate is also increased with 2%~5% speed.Mesh
Before think that T1DM is the autoimmune disease that is selectively destroyed of B cell that T cell mediates, T1DM patient in heredity and
Under the collective effect of environmental factor, cause selective destruction B cell, insulin (insulin, Ins) caused absolutely to lack,
Blood glucose rise, to cause T1DM.Establish comparatively ideal animal model has to study the pathogenesis of the disease, prevent and treat
Significance.Common diabetes animal model has experimental diabetic animal models and Spontaneous Diabetic animal model.It lures
There are many drug for leading animal generation diabetes, wherein pancreas islet of the streptozotocin (streptozotocin, STZ) to experimental animal
B cell has the toxic effect of high selectivity, and relatively small to body tissue toxicity, and modeling long-time stability are good, are mesh
It is preceding to be commonly used to prepare the drug of diabetes animal model both at home and abroad；And low dose of multiple injection STZ, so that immunocyte is infiltrated pancreas
T1DM, the more Development process close to mankind T1DM occur for island, induction C57BL/6J mouse.
Compared with ethyl alcoh(ol), edible distillate spirit manufacture craft is special, contains the biological active matters such as pyrazine compounds, terpenes
Matter.Modern study has research to think to drink and may increase the micro- blood of T1DM patient to drinking with the relationship of diabetes there are still arguement
Pipe complication separately has research then to show that responsible drinking can improve Ins sensibility.It is mainly to the research for diabetes of drinking at present
To the periodic investigation return visit of diabetes alcohol user and lanqin oral solutions, have many advantages, such as that easy, the field of investigation is wide, but be vulnerable to
The influence of surveyee's individual factor, experimental period is long, and funds in need are higher.And animal model be more common in potable spirit rather than
Edible distillate spirit, and lack related Morphological data.
Invention content：
The present invention simulates glycosuria on the basis of foundation relatively stablizes and drinks mouse model and diabetic mouse model by mouse
Patient drinks edible distillate spirit, can preferably make up the defect of above-mentioned experiment, and concern different onset time point various dose is drunk
Influence to blood glucose in diabetic mice, pancreas islet provides certain basic data for diabetes patient's responsible drinking.
To achieve the goals above, the technical solution adopted by the present invention is as follows：
The male C 57 BL/6 J mouse of a weight 18-20g, adaptable fed 1 week；It is divided into low dose group and high dose group, even
Continuous gavage is drunk to materials, 1 time a day；Low dose group drinks dosage for 2.5ml/kg, and high dose group drinks dosage for 5ml/kg.
STZ 40mg/kg were injected intraperitoneally in the 5th week in b, 1 time a day, continuous injection 5 days.
C takes tail point blood to survey fasting blood-glucose on the the 3rd, 7,10,14,21,28 day from after starting intraperitoneal injection STZ, takes tail of pancreas tissue.
Compared with the prior art, the present invention drinks edible distillate spirit by mouse, establishes type 1 diabetes mouse model, simulation
Diabetes patient drinks, and the morphological change of concern mice pancreatic original position has preferable stability and repeatability.
Description of the drawings
Fig. 1 is that immunohistochemistry shows that B cell, the expression of scale=40 μm, observation B cell Ins change.
Fig. 2 is the average optical density value of B cell, the expression quantity variation of detection B cell Ins
Fig. 3 is the face number density value of B cell, detects the change of B cell quantity
It is that diabetes are drunk mouse model and the contrast experiment of mouse model and diabetic mouse model of drinking merely below：
A drinks merely low dose group (LDG, n >=6), high dose group (HDG, n >=6), and diabetes are drunk low dose group (D-
LDG, n >=6), high dose group (D-HDG, n >=6) drunk by gavage, dosage of drinking is low dosage 2.5ml/kg, high agent
Amount group 5ml/kg, 1 times/day, continuous gavage is extremely drawn materials.
Drink group (n >=6) and diabetes group (DG, n >=6) of diabetes passes through STZ is injected intraperitoneally from b gavages the 5th week
40mg/kg, continuous 5 times, establishes T1DM mouse models by 1 times/day.Blank control group (BCG, n=3) does not do specially treated.
C each groups mouse respectively takes tail point blood to survey fasting blood-glucose on the the 3rd, 7,10,14,21,28 day after starting to inject STZ.
Every group takes tail of pancreas tissue respectively：It is respectively used to immunohistochemistry and real-time PCR.
Experimental result：
1. as shown in table 1, fasting blood sugar drinks merely group without significant change；Diabetes and diabetes are drunk high dose group
Fasting blood sugar starts to increase (P for 14 days<0.05), diabetes low dose group of drinking then begins to ramp up (P in 21 days<0.05), high
In diabetes mice at mould standard 11.1mmol/L, diabetes model is prompted to set up.
2. ImmunohistochemistryResults Results are as shown in Figure 1, compared with BCG, DG, D-LDG, D-HDG mouse prolong with the injection STZ times
Long B cell is reduced in progressive, and most of B cell immune response gradually weakens, but a small amount of remaining B cell immune response is increased
By force.Each time point mouse islets B cell Ins average optical density values measurement result is as shown in Fig. 2, the simple apparent change of group nothing of drinking
Change.Diabetes group, diabetes drink group in the 7th, 10,14 day be in higher level, prompt the compensatory of undamaged B cell
Property secretion Ins increase.
3. as shown in Fig. 3 and table 2, each time point blank control group, a simple group mouse islets B cell face number density of drinking,
Ins mRNA differential expressions are not statistically significant；Diabetes group, diabetes, which drink to organize, to be continuously decreased from 7 days, and B cell damage is prompted
Wound is gradually accumulated, and the miopragia for secreting Ins is even lost.
This patent is described in detail above with reference to specific implementation mode, in dosage of drinking, duration and the drink of this patent setting
The damage of T1DM mouse islets B cells is not aggravated in wine type, can be provided for diabetes patient's responsible drinking certain reference according to
According to.
1 fasting blood sugar testing result (mmol/L) of table
Compared with blank control group, low dose group of drinking and high dose group of drinking△P<0.05,*P<0.01
The transcriptional level of Ins mRNA in 2 pancreatic tissue of table
Compared with BCG, LDG, HDG△P<0.05,*P<0.01。
Claims (3)
1. 1.1 patients with type Ⅰ DM mouse responsible drinking model of claim, specific construction method are as follows：
A selects the male C 57 BL/6 J mouse of weight 18-20g, adaptable fed 1 week；
B continuous gavages are drunk to materials；
Streptozotocin 40mg/kg is injected intraperitoneally in c gavages from the 5th week, 1 time a day, continuous injection 5 days；
D takes tail point blood to survey fasting blood for the 3rd day, 7 days, 10 days, 14 days, 21 days, 28 days after starting that streptozotocin is injected intraperitoneally
Sugar takes tail of pancreas tissue.
2. model building method of the claim 2. according to claim 1 further includes drinking type for 54 ° of Dong Jius.
3. model building method of the claim 3. according to claim 1,2, drinks and is divided into low dose group and high agent
Amount group, low dose group of drinking are 2.5ml/kg, high dose group 5ml/kg, daily gavage 1 time.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710180212.6A CN108619162A (en) | 2017-03-24 | 2017-03-24 | The construction method of type 1 diabetes mouse responsible drinking model |
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|---|---|---|---|
| CN201710180212.6A CN108619162A (en) | 2017-03-24 | 2017-03-24 | The construction method of type 1 diabetes mouse responsible drinking model |
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| CN108619162A true CN108619162A (en) | 2018-10-09 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101601863A (en) * | 2008-06-13 | 2009-12-16 | 上海师范大学 | A kind of construction method of diabetes animal model |
| CN102812921A (en) * | 2012-09-04 | 2012-12-12 | 东北师范大学 | Method for establishing type 2 diabetes animal model and application of type 2 diabetes animal model in screening of blood sugar reducing medicaments |
| CN106377529A (en) * | 2016-11-10 | 2017-02-08 | 广西中医药大学 | Method for quickly making models of diabetic mice |
-
2017
- 2017-03-24 CN CN201710180212.6A patent/CN108619162A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101601863A (en) * | 2008-06-13 | 2009-12-16 | 上海师范大学 | A kind of construction method of diabetes animal model |
| CN102812921A (en) * | 2012-09-04 | 2012-12-12 | 东北师范大学 | Method for establishing type 2 diabetes animal model and application of type 2 diabetes animal model in screening of blood sugar reducing medicaments |
| CN106377529A (en) * | 2016-11-10 | 2017-02-08 | 广西中医药大学 | Method for quickly making models of diabetic mice |
Non-Patent Citations (2)
| Title |
|---|
| 尹丹，等: ""某54° 食用白酒对大鼠血糖及胰岛A 细胞表达胰高血糖素的影响"", 《广东医学》 * |
| 张璞，等。: ""1 型糖尿病小鼠模型构建及胰岛B细胞中胰岛素表达"", 《贵阳医学院学报》 * |
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Application publication date: 20181009 |