CN110313446A - A kind of non-human primate model of hypercholesterolemia high in fat, construction method and application - Google Patents

A kind of non-human primate model of hypercholesterolemia high in fat, construction method and application Download PDF

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Publication number
CN110313446A
CN110313446A CN201910737260.XA CN201910737260A CN110313446A CN 110313446 A CN110313446 A CN 110313446A CN 201910737260 A CN201910737260 A CN 201910737260A CN 110313446 A CN110313446 A CN 110313446A
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CN
China
Prior art keywords
fat
hypercholesterolemia
construction method
model
human primate
Prior art date
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Pending
Application number
CN201910737260.XA
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Chinese (zh)
Inventor
庄永杰
吴培灿
邢柳柳
陈继巧
姜世浩
邓志豪
甘婷
沈红英
靳策
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Jiangsu Kema Qi Biotechnology Co Ltd
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Jiangsu Kema Qi Biotechnology Co Ltd
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Priority to CN201910737260.XA priority Critical patent/CN110313446A/en
Publication of CN110313446A publication Critical patent/CN110313446A/en
Pending legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027New breeds of vertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/0004Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00Modified animals
    • A01K2207/25Animals on a special diet
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/106Primate
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/03Animal model, e.g. for test or diseases
    • A01K2267/035Animal model for multifactorial diseases
    • A01K2267/0362Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes

Abstract

The invention discloses a kind of non-human primate model of hypercholesterolemia high in fat, construction method and applications, the non-human primate that 3-6 years old is raised using the common maintenance feed containing 20-35% fat and 0.75-2% cholesterol, has been successfully established the animal experimental model of hypercholesterolemia high in fat.The model is provided simultaneously with the hypercholesterolemia and hypertriglyceridemia that metabolic syndrome is caused, and can be used for the teiology of metabolic syndrome and its concurrent multi viscera lesion, pathological research and medical judgement.

Description

A kind of non-human primate model of hypercholesterolemia high in fat, construction method and Using
Technical field
The present invention relates to field of medical technology, more particularly to a kind of non-human primate of hypercholesterolemia high in fat Model, construction method and application.
Background technique
Metabolic syndrome (MS) is the pathological state of a variety of Metabolite abnormal aggregations, main to show: Central obesity or Overweight, dyslipidemia, hypertension, insulin resistance and/or impaired glucose tolerance, these metabolic disorders disease group is the heart The highly dangerous factor of vascular diseases and type II diabetes.The big health data of China in 2018 discloses China's population of being obese and reaches 3.25 hundred million.Statistics, which speculate following 20 years, will increase by 33 times by the type II diabetes that obesity causes, and cardiovascular disease is up to 3 Hundred million people, the tumour that obesity causes will increase by 8 times.The animal experimental model of hypercholesterolemia high in fat is established for metabolic syndrome Research and clinical prevention have very strong application value.The method of high cholesterol diet modeling high in fat is used under the prior art It is chiefly used in toy, such as rats and mice, hamster etc..The model of non-human primate is still in near-space white region at present.
Summary of the invention
The present invention utilizes non-human primate, machin and macaque, using special high cholesterol diet high in fat raising 8 It has been successfully established the animal experimental model of hypercholesterolemia high in fat week.The model shows as quick serum total cholesterol, low The corresponding raising of the adjoint high-density lipoprotein of the raising of density lipoprotein, at the same it is higher with a degree of triglycerides, it can For metabolic syndrome and its teiology of concurrent multi viscera lesion, pathological research and medical judgement.
The purpose of the present invention is to provide a kind of non-human primate models of hypercholesterolemia high in fat.
Another object of the present invention is to provide a kind of structures of the non-human primate model of hypercholesterolemia high in fat Construction method.
Another object of the present invention is to provide a kind of answering for the non-human primate model of hypercholesterolemia high in fat With.
Specific technical solution of the present invention is as follows:
A kind of construction method of the animal model of hypercholesterolemia high in fat feeds high cholesterol high in fat to 3-6 years old machin Feed constructs animal model, and it is 20-35%% fat and 0.75-2% gallbladder that the high cholesterol diet high in fat, which is containing mass percent, The common maintenance feed of sterol is fed daily.
High cholesterol diet high in fat of the present invention is preferably the common dimension for containing 20% fatty (lard) and 2.0% cholesterol Hold feed.
Machin of the present invention is preferably female or male, and 3-6 years old.
Construction method of the present invention, using 2 times a day, each feeding volume is every monkey of 70g/.
Construction method of the present invention, feeding preferred cycle are 8 weeks.
A kind of animal model of hypercholesterolemia high in fat, constructs to obtain using the method.
The animal model that the animal model is used for hypercholesterolemia high in fat is metabolized by a kind of application of animal model The clinical medicine of syndrome, hypercholesterolemia and hypertriglyceridemia is developed.
The present invention has the advantages that
The present invention realizes rapid modeling, 100% modeling success using specific formula and feed mode.
Blood biochemical testing result shows that the method for the invention constructs to obtain quick total cholesterol raising, low-density The metabolic syndromes machin models such as lipoprotein cholesterol increases, and a degree of triglycerides is higher, model success rate percentage Hundred, stability is good, no death rate.The blank of the animal model in the field has been filled up, has been the research of mankind's metabolic syndrome, with And new drug development provides indispensable experimental animal model.
Detailed description of the invention
The present invention is described in further detail for embodiment in reference to the accompanying drawing, but does not constitute to of the invention Any restrictions.
Fig. 1 is 8 weeks the weight of animals of animal pattern variation of the method for the invention building.
Fig. 2 is 8 weeks serum LDL-c of animal pattern variation of the method for the invention building.
Fig. 3 is 8 weeks serum hdl-c of animal pattern variation of the method for the invention building.
Fig. 4 is 8 weeks serum TGs of animal pattern variation of the method for the invention building.
Fig. 5 is 8 weeks serum TCs of animal pattern variation of the method for the invention building.
Fig. 6 is 8 weeks Serum ALTs of animal pattern variation of the method for the invention building.
Fig. 7 is 8 weeks serum ASTs of animal pattern variation of the method for the invention building.
Fig. 8 is the animal pattern 8 weeks serum GGT variation of the method for the invention building.
Specific embodiment
Illustrate specific steps of the invention by the following examples, but is not limited by the example.
Term as used in the present invention generally there are those of ordinary skill in the art usually to manage unless otherwise indicated The meaning of solution.
The present invention is described in further detail combined with specific embodiments below and referring to data.It should be understood that the embodiment is In order to demonstrate the invention, it rather than limits the scope of the invention in any way.
In the examples below, the various processes and method being not described in detail are conventional methods as known in the art.
The present invention is further described combined with specific embodiments below.
Animal: male regular grade machin, 4 years old, 15, the raising of regular grade animal feeding center, illumination/12 were small within 12 hours When no light, temperature control condition 21-25 degree, humidity control conditions 40-70 degree.Quarantine in animal 30 days enters formally after adapting to Experiment.
It is common that feed is maintained to be purchased from Pizhou City's river development in science and technology Co., Ltd.
High cholesterol diet high in fat: 20% fatty (lard)+2.0% cholesterol.
Experimental group: Normal group, 5;Model group, 10.
Feed mode: it uses 2 times a day, the morning and afternoon, every time 70 grams/every monkey, feeding cycle 8 weeks.Animal adapts to Good, the survival rate 100% of property.
Detection model animal after modeling: different time points acquire peripheral blood and separate serum, detect serum hdl-c, LDL-c, TC, TG, ALT, AST, GGT variation.
One, lipid-metabolism syndrome result of study
Fig. 1 is the weight of animals variation for feeding eight weeks.Fig. 2-8 is different in animal pattern 8 weeks of the method for the invention building Serum hdl-the c and LDL-c, TG and TC at time point, the changing rule of TG and TC and GGT.Animal pattern 8 weeks as the result is shown Inner body heavy and light degree increases (Fig. 1).Serum LDL-c caused by animal pattern lipidosis, TG, TC conspicuousness increase, and HDL-c is also There is conspicuousness to increase.What is paid particular attention to is the raising of conspicuousness ALT and AST occur in model the 8th week, with the raising of GGT Trend.This stage is prompted to start hypercholesterolemia high in fat occur to lead to hepatic injury.The experimental results showed that being lured using this method The experimental animal led presented the clinical manifestation of specific hypercholesterolemia high in fat at model the 8th week, at the same animal into Enter the incipient stage of multiple organ injury caused by hypercholesterolemia high in fat, especially easily impaired liver.
It summarizes:
The present invention gives specific high cholesterol diet high in fat to 4 years old male machin and feeds 8 weeks according to specific method for breeding, Model is waited in the experiment for constructing hypercholesterolemia high in fat, meets the morbidity basic principle of lipid-metabolism syndrome in current crowd, It can real simulation and close to the pathologic process of metabolic syndrome caused by hypercholesterolemia high in fat, model success rate percent Hundred, stability is good, no death rate.The blank of the object model in the field has been filled up, has been metabolic syndrome caused by human obesity Research, especially diabetes, NASH, coronary heart disease, the research of the major disease of nephrosis etc. and new drug development provide indispensable Few animal model.
Embodiment provided above is better embodiment of the invention, only is used to facilitate to illustrate the present invention, not to this hair It is bright to make any form of restriction, any those of ordinary skill in the art, if not departing from the proposed skill of the present invention In the range of art feature, the equivalent embodiment that part is changed or modified is made using disclosed technology contents, and Without departing from technical feature content of the invention, in the range of still falling within the technology of the present invention feature.

Claims (7)

1. a kind of construction method of the non-human primate model of hypercholesterolemia high in fat, which is characterized in that 3-6 years old Non-human primate feeds special high cholesterol diet high in fat building animal model, the high cholesterol diet high in fat be containing There is the common maintenance feed of 20-35% fat and 0.75-2% cholesterol.The modeling same day starts to be fed daily.
2. construction method as described in claim 1, which is characterized in that the high cholesterol diet high in fat is high in fat containing 20% With the common maintenance feed of 2.0% cholesterol.
3. construction method as described in claim 1, which is characterized in that the non-human primate is machin and macaque.
4. construction method as described in claim 1, which is characterized in that using 2 times a day, each total feed feeding volume is 70g/ Every monkey.
5. construction method as described in claim 1, which is characterized in that a length of 8 weeks when feeding.
6. a kind of animal model of hypercholesterolemia high in fat, which is characterized in that use the described in any item sides of claim 1-5 Method constructs to obtain.
7. a kind of application of animal model as claimed in claim 6, is used for hypercholesteremia high in fat for the animal model The clinical medicine of the animal model metabolic syndrome of disease, hypercholesterolemia and hypertriglyceridemia is developed.
CN201910737260.XA 2019-08-11 2019-08-11 A kind of non-human primate model of hypercholesterolemia high in fat, construction method and application Pending CN110313446A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111328920A (en) * 2020-03-10 2020-06-26 昆明科灵生物科技有限公司 Feed for constructing non-alcoholic steatohepatitis model of non-human primate and using method thereof
CN113796354A (en) * 2021-09-29 2021-12-17 湖北天勤生物技术研究院有限公司 Method for establishing cynomolgus monkey hypertriglyceridemia model and application thereof

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CN103314925A (en) * 2013-06-21 2013-09-25 四川大学华西医院 Method for preparing rhesus monkey type 2 diabetic model
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