CN114128672B - Construction method of autism rat model - Google Patents
Construction method of autism rat model Download PDFInfo
- Publication number
- CN114128672B CN114128672B CN202111448317.8A CN202111448317A CN114128672B CN 114128672 B CN114128672 B CN 114128672B CN 202111448317 A CN202111448317 A CN 202111448317A CN 114128672 B CN114128672 B CN 114128672B
- Authority
- CN
- China
- Prior art keywords
- autism
- rat
- day
- modeling
- days
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010003805 Autism Diseases 0.000 title claims abstract description 72
- 208000020706 Autistic disease Diseases 0.000 title claims abstract description 72
- 238000011552 rat model Methods 0.000 title claims description 12
- 238000010276 construction Methods 0.000 title abstract description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 33
- 230000000638 stimulation Effects 0.000 claims abstract description 7
- 102000006992 Interferon-alpha Human genes 0.000 claims abstract description 6
- 108010047761 Interferon-alpha Proteins 0.000 claims abstract description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960004373 acetylcholine Drugs 0.000 claims abstract description 6
- 241000700159 Rattus Species 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 15
- 238000002474 experimental method Methods 0.000 claims description 14
- 230000006399 behavior Effects 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 4
- 108010073771 Soybean Proteins Proteins 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 235000013922 glutamic acid Nutrition 0.000 claims description 4
- 239000004220 glutamic acid Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 claims description 4
- 235000019710 soybean protein Nutrition 0.000 claims description 4
- 238000010254 subcutaneous injection Methods 0.000 claims description 4
- 239000007929 subcutaneous injection Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 230000003044 adaptive effect Effects 0.000 claims description 3
- UYVOISSIMFTJPY-UHFFFAOYSA-N cyclohexylbenzene piperidine Chemical compound N1CCCCC1.C1(=CC=CC=C1)C1CCCCC1 UYVOISSIMFTJPY-UHFFFAOYSA-N 0.000 claims description 3
- 239000004744 fabric Substances 0.000 claims description 3
- 238000010171 animal model Methods 0.000 abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 18
- 208000024891 symptom Diseases 0.000 abstract description 18
- 238000011282 treatment Methods 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 5
- 230000007310 pathophysiology Effects 0.000 abstract description 4
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 230000002496 gastric effect Effects 0.000 abstract description 3
- 230000001939 inductive effect Effects 0.000 abstract description 3
- 230000002757 inflammatory effect Effects 0.000 abstract description 3
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 abstract description 3
- 229950010883 phencyclidine Drugs 0.000 abstract description 3
- 230000000049 anti-anxiety effect Effects 0.000 abstract description 2
- 239000002249 anxiolytic agent Substances 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 description 13
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 10
- 230000008506 pathogenesis Effects 0.000 description 9
- 238000011160 research Methods 0.000 description 8
- 229960000604 valproic acid Drugs 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 3
- 206010042008 Stereotypy Diseases 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000003997 social interaction Effects 0.000 description 2
- 208000027765 speech disease Diseases 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 1
- 208000012239 Developmental disease Diseases 0.000 description 1
- 101100013186 Mus musculus Fmr1 gene Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000004694 hippocampus damage Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000004796 pathophysiological change Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 230000011273 social behavior Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/02—Breeding vertebrates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
- A23K20/147—Polymeric derivatives, e.g. peptides or proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/50—Feeding-stuffs specially adapted for particular animals for rodents
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Polymers & Plastics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Husbandry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Environmental Sciences (AREA)
- Birds (AREA)
- Animal Behavior & Ethology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention aims to develop an animal model which can focus on the core symptoms of autism and can well evaluate the efficacy of the anti-anxiety autism. The model shows higher success rate and stability in inducing classical symptoms of the autism and accompanying symptoms of the autism such as high blood pressure, inflammatory factor release disorder and the like. In the construction method of the autism animal model, the animal is injected with interferon alpha, acetylcholine and phencyclidine subcutaneously, the animal is fed with high-protein feed, the day and night reversal stimulation and the citric acid gastric lavage are carried out to obtain the autism animal model, the non-single-factor induced autism animal model accords with the etiology that the autism is induced and generated by multiple factors, can better simulate the characteristics of human autism, basically accords with three effectiveness, and is an ideal animal model from the perspective of pathophysiology theory, typical clinical symptoms and treatment prediction.
Description
Technical Field
The invention belongs to the field of animal model construction, and particularly relates to a construction method of an autism rat model.
Background
Autism, also called autism, is a developmental neuropsychiatric disease which is often seen in teenagers, and patients often show behavioral and emotional abnormalities such as social disorder, repetitive stereotypy, anxiety and the like, and no effective drug treatment method is available at present. In recent years, the prevalence rate of autism in various countries around the world has increased year by year, and the basic and clinical research of autism and the research of autism animal models have become one of the hot spots in the fields of foremedicine and neuroscience. Currently, in the international range, autism is not only a medical problem, but also a social problem which gradually becomes an urgent need to be solved in the medical background. Therefore, it becomes important to improve the level of cognition and research in this disease. The animal model provides advantages superior to human body research due to the characteristics of controllability, availability, predictability and the like, plays an important role in the exploration of disease causes and pathogenesis for people, and becomes a key for exploring the relationship between a nervous system and the incidence of autism for people.
A reasonable and effective animal model is established, the cause of the autism is discussed, and the basis for understanding the etiology and pathogenesis of the autism and carrying out early screening and intervention is provided. At present, animal models of autism include environmental factor models (maternal immunity model, valproic acid model, etc.), genetics models (FMR-1 gene model, meCP-2 gene model, etc.), brain damage models (hippocampal damage model, amygdala damage model, etc.). The research on the autism model for immune activation caused by exposure of the pregnant mother to the Poly-IC is very mature, and the model not only proves the autism in development and behavior, but also is very deep in pathology, biochemistry, structure and the like. Animals used for the molding of the autistic animals are rodents and non-human primates, and the rodents are mainly used. At home and abroad, wistar rats are mostly used for establishing rodent autism models, and Sprague-Dawley rats are rarely used. Compared with the Sprague-Dawley rats, the Sprague-Dawley rats have the advantages of strong reproductive capacity, fast growth and development, strong resistance to diseases and the like.
Autism spectrum disorders are now thought to be the result of environmental and genetic factors working together. Epidemiological studies have shown that exposure of fetus to some drugs with neurotoxicity, such as valproic acid (VPA) and propionic acid, which are antiepileptic drugs, can cause development disorder of nervous system, seriously affect the development of cognitive function, and cause the generation of autism, so that the neurotoxic method is one of the important means for establishing and researching autism animal model. VPA exposure in pregnancy is a classical and common neurotoxic autism model, and after VPA is injected into an abdominal cavity of a mouse pregnant for 12.5 days, offspring of the mouse can have autism spectrum disorder-like manifestations such as reduction of social and exploratory behaviors, repeated stereotypical exercises, anxiety and tension states and the like.
At present, animal models created around the causes and pathogenesis of the autism are increased continuously, on the one hand, the academic community pays more attention to the autism, and meanwhile, the diversification of the models also creates the unimportant purpose of research. Three kinds of effectiveness are widely used for evaluating the closeness degree of a model and human diseases by observing the evaluation standards of the animal model internationally and domestically. The more effective the model is presented, the better its presentation on human diseases. These effectiveness are not only crucial in assessing the reliability of animal models, but they are also not alternatives in assessing the efficacy of drug treatments. The first is structural validity, i.e., the model should conform to a certain theoretical hypothesis and the pathophysiological changes should be consistent with the hypothesis or theory. The second is surface validity, i.e. the model is able to model the typical characteristics of the disease in many ways, such as behavioural. In an autism animal model, typical clinical symptoms such as stereotypy behaviors, social interaction, speech disorder and the like can be simulated, and the good surface effectiveness is achieved. The third is the prediction effectiveness, that is, the pharmacological response and non-pharmacological response of the model are consistent with the clinical treatment performance, and the model can provide the prediction for the long-term treatment and the pathogenesis research. In summary, autism is a complex developmental disorder disease, and genetic abnormalities, brain dysfunction, etc. are the direction of recent continuous exploration. The onset of autism is closely related to various factors, and at present, people grasp some susceptibility factors through various ways such as epidemiological data, clinical observation and the like, but the understanding of the disease is far from enough. The full exploitation and utilization of animal models is the best choice for researching the pathogenesis and the treatment method of the autism. Current models do not have ideal pathology and etiology models that meet three fundamental efficiencies.
Disclosure of Invention
The invention aims to develop an animal model which can focus on the core symptoms of autism and can well evaluate the efficacy of anti-anxiety autism. The model shows higher success rate and stability in inducing classical symptoms of the autism and accompanying symptoms of the autism such as high blood pressure, inflammatory factor release disorder and the like.
The invention is realized by the following technical scheme:
a method for constructing an autism rat model is characterized by comprising the following steps:
(1) And subcutaneous injection: selecting male rats with the age of 4 weeks, and adaptively feeding for 1 week; modeling lasted for 30 days. After the adaptive feeding is finished, 50 mu g/kg of interferon alpha is injected to the rat subcutaneously on the 1 st and 10 th days of modeling respectively, 10 mu g/kg of acetylcholine is injected to the rat subcutaneously on the 2 nd and 15 th days respectively, and 8 mu g/kg of phenylcyclohexane piperidine (PCP) is injected to the rat subcutaneously on the 20 th day.
(2) Feeding high-protein feed: feeding a high-protein feed to the rats on the 1 st to 28 th days of modeling, wherein the high-protein feed is prepared by adding 10% of soybean protein powder, 5% of sodium cholate and 0.2% of glutamic acid by mass of a basic feed.
(3) Day and night reversal stimulation: during the 30 days of modeling, the raising environment of the rat is reversed day and night, namely the rat raising box is wrapped by black cloth in the day to create a dark environment, and an illuminating lamp of the rat raising box is turned on at night.
(4) And citric acid intragastric administration: rats were fasted on day 29 of modeling and gavaged on day 30 with 30mg/kg of citric acid; thus obtaining the rat model of the autism.
The rats were male SD rats.
After 30 days of modeling, detecting the spatial cognitive processing process and the memory capacity of the rat through the detection of the weight change of the rat, an open field experiment, a three-box social experiment, a social preference test and a water maze experiment, and the result shows that the rat expresses typical self-closure behavior and accords with the judgment and treatment of the reliability and the effectiveness of an autism animal model, namely the pathogenesis, the symptom expression and the pathophysiology of the disease.
The technical scheme of the invention has the following advantages:
1. according to the construction method of the autism animal model, the animal model of the autism is obtained by injecting interferon alpha, acetylcholine and phencyclidine to the animal subcutaneously, feeding high-protein feed, reversing stimulation day and night and performing gastric lavage by citric acid, and the non-single-factor induced autism animal model accords with the etiology that the autism is considered to be multi-factor induced, so that the characteristics of human autism can be better simulated. The non-single-factor induced autism animal model basically accords with three effectiveness, is an ideal animal model from the perspective of pathophysiology theory, or the perspective of simulating typical clinical symptoms and treating prediction, provides support for a multi-factor induced pathogenesis of autism, and provides a theoretical basis for developing a new scheme for treating the autism.
2. The established autism animal model has stable effect and small individual difference; the multiple factors are mutually cooperated, and the constructed disease model is more accurate. The model shows higher success rate and stability in inducing classical symptoms of the autism (typical clinical symptoms such as simulated stereotypy behavior, social interaction, speech disorder and the like) and accompanying symptoms of the autism such as high blood pressure, inflammatory factor release disorder and the like.
3. The autism animal model disclosed by the invention is a non-single-factor induced autism animal model, provides support for a multi-factor induced pathogenesis of autism, better simulates the advantage of slow progress of human autism, and provides an important theoretical basis for developing a new pharmaceutical preparation for effectively treating autism. The method can be used for exploring the scientific connotation of multiple factors on the autism and providing an animal model capable of reflecting the essence of diseases for screening new drugs.
4. The invention adopts an induction mode of combining subcutaneous injection of interferon alpha, acetylcholine and phencyclidine, and the three reagents can be mutually reinforced in a synergistic way while playing roles respectively, so that the generation of autism can be excellently induced. Through multiple tests and verification, the injection time and the injection dosage of the three reagents are optimized, and a more accurate rat model of the autism is ensured.
5. The invention also adopts an induction method of feeding high protein feed and citric acid for gastric perfusion, can better simulate the causes and symptoms of clinical autism of traditional Chinese medicine, and can excellently induce classical symptoms and accompanying symptoms of autism by combining with three reagents for injection and day-night reversal stimulation. The inventor screens out a high-protein feed formula of the basal feed added with 10 percent of soybean protein powder, 5 percent of sodium cholate and 0.2 percent of glutamic acid through numerous creative labor and scientific experiments, is very suitable for feeding rats, and is extremely beneficial to clinical simulation of etiology and disease symptoms of autism. The last day of modeling is perfused with 30mg/kg of citric acid, which plays a role of drawing dragon dots in the research and ensures the stable effect of the autism rat model.
Detailed Description
A method for constructing an autism rat model is characterized by comprising the following steps:
(1) And subcutaneous injection: selecting male rats with the age of 4 weeks, and adaptively feeding for 1 week; modeling lasted for 30 days. After the adaptive feeding is finished, 50 mu g/kg of interferon alpha is injected to the rat subcutaneously on the 1 st and 10 th days of modeling respectively, 10 mu g/kg of acetylcholine is injected to the rat subcutaneously on the 2 nd and 15 th days respectively, and 8 mu g/kg of phenylcyclohexane piperidine (PCP) is injected to the rat subcutaneously on the 20 th day.
(2) Feeding high-protein feed: feeding a high-protein feed to the rats on the 1 st to 28 th days of modeling, wherein the high-protein feed is prepared by adding 10% of soybean protein powder, 5% of sodium cholate and 0.2% of glutamic acid by mass of a basic feed.
(3) Day and night reversal stimulation: during the 30 days of modeling, the raising environment of the rat is reversed day and night, namely the rat raising box is wrapped by black cloth in the day to create a dark environment, and an illuminating lamp of the rat raising box is turned on at night.
(4) And citric acid intragastric administration: rats were fasted on day 29 of modeling and gavaged on day 30 with 30mg/kg of citric acid; thus obtaining the rat model of the autism.
The rats were male SD rats.
After 30 days of modeling, detecting the spatial cognitive processing process and the memory capacity of the rat through the detection of the weight change of the rat, an open field experiment, a three-box social experiment, a social preference test and a water maze experiment, and the result shows that the rat expresses typical self-closure behavior and accords with the judgment and treatment of the reliability and the effectiveness of an autism animal model, namely the pathogenesis, the symptom expression and the pathophysiology of the disease.
Comparative experiment: the test was divided into 6 groups, group 1 using the modeling method of the present invention, group 2 using only the injection method of step (1), group 3 using only the high protein feed feeding method of step (2), group 4 using only the diurnal reversal stimulation of step (3), group 5 using only the citric acid gavage method of step (4), group 6 being a blank control group. After 30 days of modeling, through detection of weight change of rats, open field experiments, three-box social experiments, social preference tests and water maze experiments, results show that the 1 st group successfully constructs a typical autism rat model, rats in the 2 nd to 5 th groups only show self-closing autism to a certain extent, but do not sufficiently meet the standard of an autism animal model, and the 6 th group shows normal performance.
Claims (2)
1. A method for constructing an autism rat model is characterized by comprising the following steps:
(1) And subcutaneous injection: selecting male rats with the age of 4 weeks, adaptively feeding for 1 week, and modeling for 30 days; after the adaptive feeding is finished, injecting 50 mug/kg of interferon alpha to the rat subcutaneously on the 1 st and 10 th days of modeling respectively, injecting 10 mug/kg of acetylcholine to the rat subcutaneously on the 2 nd and 15 th days respectively, and injecting 8 mug/kg of phenylcyclohexane piperidine (PCP) to the rat subcutaneously on the 20 th day;
(2) Feeding high-protein feed: feeding a high-protein feed to a rat on the 1 st to 28 th days of modeling, wherein the high-protein feed is prepared by adding 10% of soybean protein powder, 5% of sodium cholate and 0.2% of glutamic acid by mass of a basic feed into the basic feed;
(3) Day and night reversal stimulation: during the modeling period of 30 days, the raising environment of the rat is reversed day and night, namely the rat raising box is wrapped by black cloth in the day to create a dark environment, and an illuminating lamp of the rat raising box is turned on at night;
(4) And citric acid intragastric administration: rats were fasted on day 29 of modeling and gavaged on day 30 with 30mg/kg of citric acid; obtaining an autism rat model; after 30 days of modeling, the rat shows typical self-closing behaviors through detection of weight change of the rat, open field experiments, three-box social experiments, social preference tests and water maze experiments.
2. The method of claim 1, wherein the rat is a male SD rat.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111448317.8A CN114128672B (en) | 2021-11-21 | 2021-11-21 | Construction method of autism rat model |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111448317.8A CN114128672B (en) | 2021-11-21 | 2021-11-21 | Construction method of autism rat model |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114128672A CN114128672A (en) | 2022-03-04 |
| CN114128672B true CN114128672B (en) | 2023-04-07 |
Family
ID=80386429
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111448317.8A Active CN114128672B (en) | 2021-11-21 | 2021-11-21 | Construction method of autism rat model |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114128672B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114766430B (en) * | 2022-04-29 | 2023-04-25 | 武汉大学 | Construction method and application of fetal-derived autism animal model |
| CN115053861A (en) * | 2022-06-30 | 2022-09-16 | 南方医科大学南方医院 | Construction method and application of animal model of schizophrenia based on immune activation |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2851163B1 (en) * | 2003-02-14 | 2007-04-27 | USE OF DEXTROGYAN ENANTIOMER OF MILNACIPRAN FOR THE PREPARATION OF A MEDICINAL PRODUCT | |
| PL2667715T3 (en) * | 2011-01-27 | 2018-02-28 | Neuren Pharmaceuticals Limited | Treatment of autism spectrum disorders using glycyl-l-2-methylprolyl-l-glutamic acid |
| CN104450602B (en) * | 2013-09-17 | 2020-08-07 | 中国科学院遗传与发育生物学研究所 | Non-human mammal animal model of neuropsychiatric disease and preparation method and application thereof |
| KR20210041379A (en) * | 2019-10-07 | 2021-04-15 | 건국대학교 글로컬산학협력단 | Methods of making autistic behavior model mice |
| CN112237156B (en) * | 2020-10-23 | 2022-07-22 | 宁波大学 | Autonomous social behavior testing device and experimental method for small animals |
| CN113040090A (en) * | 2021-04-13 | 2021-06-29 | 南京医科大学 | Method for constructing animal model of autism and corresponding application |
-
2021
- 2021-11-21 CN CN202111448317.8A patent/CN114128672B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN114128672A (en) | 2022-03-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114128672B (en) | Construction method of autism rat model | |
| Schulte | Social structure and helping behavior in captive elephants | |
| CN104798728A (en) | Creation method and applications of postpartum depression animal models | |
| CN104542389B (en) | Preparation method for non-alcoholic fatty liver disease zebra fish | |
| CN104885956A (en) | Sow positioning fence | |
| CN101461341A (en) | Induced spawning method of Brachymystax lenok | |
| CN109997787B (en) | Method for breeding rat with non-alcoholic steatohepatitis transformed into hepatocellular carcinoma and application | |
| CN108938667B (en) | Method for constructing Alzheimer's disease model for drug screening | |
| CN202603405U (en) | Giant salamander breeding pond | |
| CN101595847B (en) | Method for inducing Stichopus Japonicus Selenka to lay eggs in vivo | |
| CN103830721A (en) | Derivant of establishing rheumatoid arthritis animal model, preparation and application thereof | |
| CN114946752B (en) | Construction method of depression mouse model | |
| CN102232963A (en) | Method for establishing ulcerative colitis chemically cancer-induced animal model | |
| CN113575516B (en) | Method for establishing type II diabetes rat model | |
| CN201101059Y (en) | Cultivation pool for penaeus orientalis | |
| Gale | The embryotoxic response produced by inorganic mercury in different strains of hamsters | |
| CN107929269B (en) | Method for preparing hepatic fibrosis animal model by using juvenile zebra fish | |
| CN103405787A (en) | Molecular targeted nucleic acid nano-medicament based on miR-141 (micro ribonucleic acid-141), preparation and application thereof | |
| CN110317866A (en) | Schizophrenia disease mouse model hippocampus circRNA sequencing analysis and kit | |
| CN108310125A (en) | The glad application in antithrombotic reagent in forefront | |
| CN104083345A (en) | Application of lycopene in preparation of medicine for prevention and treatment senile dementia | |
| CN103301137A (en) | Application of aspirin in treatment of cognitive and behavioral disorders after epilepsy | |
| CN116369249B (en) | Construction method of zebra fish enteritis model | |
| CN107028956A (en) | A kind of pharmaceutical composition for treating menstrual period depression | |
| Ragab et al. | Recipient maternal genotypes improved the litter size components of a paternal line involved in a MOET programme in rabbits |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |