CN109172576A - A kind of Animal Models of Psoriasis construction method - Google Patents
A kind of Animal Models of Psoriasis construction method Download PDFInfo
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- CN109172576A CN109172576A CN201811095954.XA CN201811095954A CN109172576A CN 109172576 A CN109172576 A CN 109172576A CN 201811095954 A CN201811095954 A CN 201811095954A CN 109172576 A CN109172576 A CN 109172576A
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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Abstract
The present invention relates to animal model fields, in particular to a kind of Animal Models of Psoriasis construction method.The construction method includes generating Pigs with Psoriasis using animal of the imiquimod induction in anxiety state.The mouse constructed can not only embody the anxiety state that clinical patients usually occur, and Pigs with Psoriasis aggravates therewith, moreover it is possible to extend holding time for imiquimod induction Pigs with Psoriasis model.
Description
Technical field
The present invention relates to animal model fields, in particular to a kind of Animal Models of Psoriasis construction method.
Background technique
Psoriasis (Psoriasis) is commonly called as " psoriasis ", and traditional Chinese medicine is referred to as " Bai Mange ", it is a kind of with lymphocyte exception
The common chronic inflammatory skin disease that activation, the differentiation of keratinocyte abnormality proliferation and inflammatory cell infiltration are characterized,
Main Tissues pathological characters include: that epidermis inner cell parakeratosis or hyperkeratinization, intradermal blood vessel expand distortion, a variety of inflammatories
Cellular infiltration etc..Since its course of disease is long, skin lesion is extensive, often brings and seriously affects to patient's physical and mental health.
Studying the human diseases cause of disease, pathogenesis, a kind of important tool for the treatment of method is animal model, and psoriasis is rare
Any non-human animal is seen, and the case of Lock-in is extremely rare, is unsuitable for carrying out scientific research.Therefore, silver bits are established
Sick animal model seems particularly necessary.In psoriasis experiments research, animal model is selected to be very important.Modern medicine is
Psoriasis is defined as typical psychosomatic disease, and there is no can embody this clinical practice feelings for current Animal Models of Psoriasis
Condition, can only show simple skin lesion lesion, and model hold time it is shorter.
In view of this, the present invention is specifically proposed.
Summary of the invention
The purpose of the present invention is to provide a kind of Animal Models of Psoriasis construction method, the construction method is using miaow
Not special animal of the induction in anxiety state of quinoline generates Pigs with Psoriasis, so that mouse is embodied clinical patients and usually goes out
Existing anxiety state, Pigs with Psoriasis aggravate therewith, moreover it is possible to extend the maintenance of imiquimod induction Pigs with Psoriasis
Time.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of Animal Models of Psoriasis construction method, comprising: produced using animal of the imiquimod induction in anxiety state
Raw Pigs with Psoriasis.
Compared with prior art, the invention has the benefit that
(1) can aggravate Animal Models of Psoriasis: Pigs with Psoriasis PASI scoring of the present invention is higher than simple smearing miaow quinoline not
Special group, the exacerbation for the Pigs with Psoriasis that display stress cause imiquimod to induce, and epidermal thickness is not also above simple miaow quinoline
Special group, skin lesion nerve peptide content is higher than simple imiquimod group, show that skin lesion nerve peptide content and epidermis are thick through correlation analysis
Degree is positively correlated, and prompts to increase the increase for resulting in skin lesion epidermal skin thickness there are the secretion of the neuropeptide of skin lesion part.
(2) can extend Animal Models of Psoriasis: the simple psoriasis model for smearing imiquimod induction is maintaining 7 days or so
Model voluntarily subsides, and the Pigs with Psoriasis model scales of skin that peel off of the invention, erythema and infiltration can extend subsides again after a week.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is the mouse elevated plus-maze trajectory diagram in experimental example 1.1 of the present invention；
Fig. 2 is that the mouse elevated plus-maze in experimental example 1.1 of the present invention enters the time of open arms and enters closure arm
Frequency statistics figure；
Fig. 3 is the mouse spacious field experimental traces figure in experimental example 1.2 of the present invention；
Fig. 4 is the activity time and distance statistics figure during the mouse spacious field in experimental example 1.2 of the present invention is tested in central area；
Fig. 5 is the 4th day mouse weight statistical chart in experimental example 2 of the present invention；
Fig. 6 is the 7th day mouse weight statistical chart in experimental example 2 of the present invention；
Fig. 7 is the 14th day mouse weight statistical chart in experimental example 2 of the present invention；
Fig. 8 is mouse weight line chart in the empty bottle stimulating course in experimental example 2 of the present invention；
Fig. 9 is the 4th day, 7 days and 14 days mouse Pigs with Psoriasis photograph in experimental example 3 of the present invention；
Figure 10 is that the 4th day, 7 days and 14 days mouse Pigs with Psoriasis PASI in experimental example 3 of the present invention counts broken line
Figure；
Figure 11 be experimental example 4 of the present invention in mouse skin lesion in the 4th day, 7 days and 14 days at organize HE coloration result figure；
Figure 12 be experimental example 4 of the present invention in mouse skin lesion in the 4th day, 7 days and 14 days at organize epidermal thickness statistical chart；
Figure 13 is the expression that Western blot in experimental example 5 of the present invention detects neuropeptide at mouse skin lesion in the 7th day
Amount；
Figure 14 is the expression that Western blot in experimental example 5 of the present invention detects neuropeptide at mouse skin lesion in the 7th day
The statistical chart of amount；
Figure 15 is IMQ+ES group and the neuropeptide at the epidermal thickness of IMQ group and corresponding skin lesion in experimental example 5 of the present invention
The Pearson correlation coefficients linear graph of SP relative expression quantity.
Specific embodiment
The present invention provides a kind of Animal Models of Psoriasis construction methods, comprising: is in anxiety using imiquimod induction
The animal of state generates Pigs with Psoriasis.
Imiquimod (imiquimod, IMQ) is the specificity of Toll-like receptor (tolllike receptor, TLR) 7/8
Activator, can specificity and plasmacytoid dendritic cellss (plasmacytoid dendriticcells, pDC) endosome
TLR7 is combined, and induction pDC secretes a large amount of interferon (interferon, IFN)-α.
The patient that IMQ is applied to have psoriasis to be inclined to can induce and aggravate the state of an illness, thus researcher will be used for mouse and at
Function induces Psoriasis-like Pathological Changes.Psoriasis compared to formation such as other heteroplastic transplantations, gene knockout or gene mutations is small
Mouse model, IMQ induction Pigs with Psoriasis mouse model are to induce to generate under natural immunity state, are a research silver bits
The more preferably mouse model of disease and its therapeutic agent is usually used in exploring the drug effect of various treatment psoriasis.
The present invention compound Anxiety Model on the basis of imiquimod induces, not only enables mouse embody clinical patients normal
The anxiety state often occurred, Pigs with Psoriasis aggravate therewith, moreover it is possible to extend imiquimod induction Pigs with Psoriasis
It holds time.
In some embodiments, the method for generating the anxiety state is using empty bottle stimulating exercise.
It is the typical model for causing murine chronic emotional stress that empty bottle, which stimulates model, can be used for the observation of animal behavioral study method and answers
The attack of mouse after swashing is probed into, the experiment such as the variation of grooming behavior.
In some embodiments, the method for the empty bottle stimulating exercise includes: to have adapted to timing with the stimulation of random empty bottle
The animal to drink water.
In some embodiments, the time that the timing is drunk water is once in the morning and once at night.
In some embodiments, the period that the adaptation timing is drunk water is greater than 7 days；Further preferably 7~8 days.
It in some embodiments of the invention, further include that animal single cage is made to adapt to new ring before the empty bottle stimulating exercise
Border 1 week, stroke animal (3min/d) daily during this period is influenced with mitigating operation.
In some embodiments of the invention, the time that the timing is drunk water be daily 9:00~9:10 and 21:00~
21:10.Any water is not given among time twice.
In some embodiments, the time of the stimulation is 13~15d.
The time of the stimulation can also be 14d (result is almost the same in range).
In some embodiments of the invention, random empty bottle stimulation has water and anhydrous water bottle to be assigned randomly to each small
Mouse, drinking-water time and drinking-water duration are identical as during training.
In some embodiments, the animal after the empty bottle stimulating exercise is given to Behaviors survey to confirm anxiety
State.
In some embodiments, the Behaviors survey includes Elevated plus-maze and spacious field experiment.
Elevated plus-maze and spacious field experiment, are all the more representative experiments of anxiety behaviouristics.Elevated plus fan
Palace is a kind of unconditioned reflex model with the spontaneous frightened sample reaction of animal for behaviouristics basis.It both can establish anxiety stress
Model, and the method for classical measurement anxiety symptom generally acknowledged in the world.It has been widely used in the grinding tooths such as rat and mouse
The ethological research of class animal anxiety.
In some embodiments, the method for imiquimod induction includes: daily in being confirmed as the dynamic of anxiety state
It is 6~8mg/cm that object skin of back, which smears surface density,2Imiquimod.
The smearing surface density can also be 7mg/cm2(result is almost the same in range).
In some embodiments of the invention, it after Elevated plus-maze and spacious field experiment, gives and is confirmed as anxiety state
Mouse shaving, back of mice long hair is rejected using hair cutter, then with disposable preparation skin knife by the undercoat left send out or
Fine hair strikes off, and back of mice is made to expose the hairless region of about 2cm × 3cm rectangle to smear imiquimod.
In some embodiments, the concentration of the imiquimod is 4.5~5.5%.
The concentration of the imiquimod can also be 5% (result is almost the same within the scope of this).
In some embodiments, the time of the induction is 13~15d.
The time of the induction can also be 14d (result is almost the same within the scope of this).
In some embodiments, while the imiquimod induces, the random empty bottle stimulation is carried out to keep
State anxiety state.
While by the mouse progress imiquimod induction for anxiety state is had confirmed that, continue empty bottle stimulation test.
In some embodiments, the animal includes rat and mouse.
Preferably, the animal is mouse.
In some embodiments, the research of psoriasis is used for using the Animal Models of Psoriasis that method of the invention constructs
The therapeutic effect of psoriasis is evaluated with drug.
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
It can be with conventional products that are commercially available.
Embodiment 1
The selection and raising of experimental animal: male SPF grades of BALB/c mouse, 6~8 week old, weight (20 ± 2) g, China
Food and medicine examines and determine research institute, animal credit number SCXK (capital) 20140013.Mouse raising is in ventilation, clean animal house
In, it controls room temperature (20 ± 2) DEG C, relative humidity (40-70) %, 12h illumination and 12h dark cycle carry out, in addition to emotional stress
Period, all mouse freely ingest, drink water.
Mouse single cage shakes down 1 week, and stroke animal (3min/d) daily during this period is influenced with mitigating operation.One week
Afterwards, training mouse drinks water in daily 9:00~9:10 and 21:00~21:10, does not give any water during this is trained twice.
After a week, being changed to random empty bottle stimulation has water and anhydrous water bottle to be assigned randomly to each mouse, drink water time and drinking-water for training
Duration is identical as during training, and daily guarantee middle twice once has water, and stimulation time is two weeks.If there is the i.e. non-empty bottle of control
Stimulation group mouse, then empty bottle stimulation group mouse and non-empty bottle stimulation group mouse are not shared a room raising, with mitigation to non-stimulated group of the heart
Reason influences.
After two weeks, Elevated plus-maze and spacious field experiment are carried out.
Elevated plus-maze by two opposing open arms (30cm long × 8cm wide) and two relatively closed arm 30cm long ×
8cm wide × 15cm high) and central area (8cm × 8cm) be formed by connecting.Mouse is firstly placed on field and move freely 5min before testing,
Mouse head is put into middle section towards open arms direction, and mouse enters open arms and enters number, residence time, closure arm in record 5min
Into number, residence time, and open arms residence time ratio is calculated, open arms enter number ratio.Into open arms number
And the anxiety of residence time and mouse is negatively correlated, fewer into open arms number, the residence time is shorter, illustrates mouse
Anxiety is more serious.The experiment is carried out in 9:00-15:00, labyrinth ambient light secretly will hang black-out cloth when necessary；Every
Animal is placed in same position.
Open field test: using the spacious field case for being equipped with video camera, and being connected with record system.The bottom of chest is divided into
Upper left, lower-left, upper right, the angle of bottom right four；The up, down, left and right of spacious field case are about four sides；Remaining part is middle section；
Four angles of spacious field case and four sides form neighboring area.Every mouse is put into case, the work in detection mouse 10min in case
Emotionally condition records movable total time and distance relevant information of the every mouse in each region.After every mouse finishes experiment
By it, excrement, urine are thoroughly cleaned in the case, prevent rear mouse from following the track carry out activity of one mouse in front.
After Elevated plus-maze and spacious field experiment, the mouse shaving for being confirmed as anxiety state is given, line first carries on the back mouse
Minister's hair is rejected, then is struck off the undercoat left hair or fine hair with disposable preparation skin knife, and back of mice is made to expose about 2cm
The hairless region of × 3cm rectangle.
Continuing random empty bottle stimulates 2 weeks, and uses 5% imiquimod cream (the bright glad limited duty of medicine company in Sichuan during this period
Ren company, lot number 20140828) daily smear back of mice glabrous skin, each 36mg~48mg, once a day.After 2 weeks, silver
Sick animal model building is considered to be worth doing to complete.
Embodiment 2
The selection and raising of experimental animal: male SPF grades of BALB/c mouse, 6~8 week old, weight (20 ± 2) g, China
Food and medicine examines and determine research institute, animal credit number SCXK (capital) 20140013.Mouse raising is in ventilation, clean animal house
In, it controls room temperature (20 ± 2) DEG C, relative humidity (40-70) %, 12h illumination and 12h dark cycle carry out, in addition to emotional stress
Period, all mouse freely ingest, drink water.
Mouse single cage shakes down 1 week, and stroke animal (3min/d) daily during this period is influenced with mitigating operation.One week
Afterwards, training mouse drinks water in daily 9:00~9:10 and 21:00~21:10, does not give any water during this is trained twice.
After a week, being changed to random empty bottle stimulation has water and anhydrous water bottle to be assigned randomly to each mouse, drink water time and drinking-water for training
Duration is identical as during training, and daily guarantee middle twice once has water, and stimulation time is two weeks.If there is the i.e. non-empty bottle of control
Stimulation group mouse, then empty bottle stimulation group mouse and non-empty bottle stimulation group mouse are not shared a room raising, with mitigation to non-stimulated group of the heart
Reason influences.
By post-stimulatory mouse shaving, first back of mice long hair is rejected, then short by what is left with disposable preparation skin knife
Hair or fine hair strike off, and back of mice is made to expose the hairless region of about 2cm × 3cm rectangle.
Continuing random empty bottle stimulates 2 weeks, and uses 5% imiquimod cream (the bright glad limited duty of medicine company in Sichuan during this period
Ren company, lot number 20140828) daily smear back of mice glabrous skin, each 36mg~48mg, once a day.After 2 weeks, silver
Sick animal model building is considered to be worth doing to complete.
Experimental example 1
Behaviors survey.
1.1 Elevated plus-maze
Blank control group is set based on embodiment 1, i.e., without empty bottle stimulating exercise, remaining with 1 phase of embodiment
Together, the result is shown in Figure 1 and Fig. 2.
Show that blank control group (C group) mouse enters open arms number (frequency) in elevated plus and the time is bright in Fig. 1
Aobvious to be higher than empty bottle stimulating exercise group (ES group), Fig. 2 is that its statistical results chart is (left: time comparison diagram；It is right: frequency comparison figure).
Illustrate that ES group mouse has apparent anxiety-like behavior.
The experiment of 1.2 spacious fields
Experimental setup and experiment are compared by experimental example 1 and embodiment 1, as a result sees Fig. 3 and Fig. 4.
Fig. 1 the results show that C group mouse in the activity time of spacious field central area and distance obviously higher than ES group, therefore prove
ES group mouse has apparent anxiety-like behavior.Fig. 2 is that its statistical results chart is (left: in spacious field central area activity time comparison diagram；
It is right: the distance versus figure with spacious field central area).
Experimental example 2
The changes of weight of mouse model
Mouse is divided into 4 groups: blank control group (C group), empty bottle stimulating exercise group (ES group), imiquimod induction group (IMQ
Group), empty bottle stimulating exercise collaboration imiquimod induction group (IMQ+ES group), experimental method reference implementation example 1.Every group of experiment does one
Secondary parallel laboratory test.
The weight of mouse is weighed in 4d, 7d, 14d respectively, statistical results chart is shown in Fig. 5,6,7.
And count one group of C group and ES group and be drawn in curve graph (Fig. 8) in the weight value of 0d, 7d, 14d, 21d, 28d, from figure
In as can be seen that empty bottle stimulating exercise can reduce mouse weight.
The results show that i.e. variant with C group in the 7th day beginning IMQ+ES group mouse weight, there were significant differences within the 14th day, and
IMQ+ES group weight is significantly lower than ES group.
Experimental example 3
The skin lesion of mouse model detects.
The method of reference experiment example 2 is grouped and tests, using the every day entry of digital photographing method, and according to psoriasis
Sample skin lesion area and severity index (psoriasis area and severity index, PASI) standards of grading, to small
Erythema, the scales of skin that peel off and infiltration thickened degree score, three's integral add up to total mark at mouse skin lesion.PASI standards of grading: 0 point, nothing；
1 point, slightly；2 points, moderate；3 points, severe；4 points, pole severe.Each group mouse integral is averaged.
Experimental result is shown in Fig. 9 and Figure 10.The results show that erythema, the scales of skin that peel off and infiltration thickened degree are equal at IMQ group mouse skin lesion
Increase, and each index of IMQ+ES group increases, explanation, which stress train, can aggravate Pigs with Psoriasis.
Experimental example 4
Mouse model skin lesion pathological change.
After mouse takes off neck execution, organized at the corresponding skin lesion of each group clip.10% formalin is fixed, through dehydration, paraffin
Embedding, slice, HE dyeing, under the microscope and take a picture.Measure epidermal thickness.
Experimental result is shown in Figure 11 and Figure 12.The results show that IMQ+ES group epidermal thickness increases, explanation, which stress train, to be aggravated
Psoriasis epidermis thickness.
Experimental example 5
The change of mouse model neuropeptide secretion.
The method of reference experiment example 2 is tested, and carries out neuropeptide at skin lesion through Western blot at the 7th day
The detection of Substance P (SP).Use reagent are as follows: Substance P (rabbit is mostly anti-, Invitrogen, PA5-44998, and 1:
200)；β-tubulin (mouse monoclonal antibody, Immunoway, YM3030,1:10000).
Experimental result is shown in Figure 13 and Figure 14, and it is further that IMQ+ES group skin lesion nerve peptide content, which is higher than IMQ group, as the result is shown
The epidermal thickness of mouse skin lesion and the relationship of neuropeptide relative expression quantity are verified, anxiety composite model mouse and IMQ model is small
The epidermal thickness of mouse and corresponding skin lesion neuropeptide SP relative expression quantity make Pearson correlation coefficients analysis.The result is shown in Figure 15, P
It is worth < 0.05, R=0.84, the relative expression quantity of the epidermal thickness and neuropeptide that prompt mouse skin lesion has certain correlation.More than
As a result illustrate to increase the increase for resulting in skin lesion epidermal skin thickness there are the secretion of the neuropeptide of skin lesion part.
Experimental example 6
It is tested as described in Example 1, observes the regression time of mouse Pigs with Psoriasis.
The results show that the psoriasis model mouse skin lesion for smearing imiquimod induction merely is maintaining 7 days or so models certainly
Row subsides.After compound empty bottle stimulating exercise, the Pigs with Psoriasis scales of skin that peel off, erythema and the infiltration of imiquimod induction can extend one
Zhou Houzai subsides.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Present invention has been described in detail with reference to the aforementioned embodiments for pipe, but those skilled in the art should understand that: its
It is still possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features
It is equivalently replaced；And these are modified or replaceed, various embodiments of the present invention skill that it does not separate the essence of the corresponding technical solution
The range of art scheme.
Claims (10)
1. a kind of Animal Models of Psoriasis construction method characterized by comprising be in anxiety state using imiquimod induction
Animal generate Pigs with Psoriasis.
2. Animal Models of Psoriasis construction method according to claim 1, which is characterized in that generate the anxiety state
Method is to use empty bottle stimulating exercise.
3. Animal Models of Psoriasis construction method according to claim 2, which is characterized in that the empty bottle stimulating exercise
Method includes: to have adapted to the animal that timing is drunk water with the stimulation of random empty bottle；
Preferably, the time that the timing is drunk water is once in the morning and once at night；
Preferably, the period that the adaptation timing is drunk water is greater than 7 days；Further preferably 7~8 days.
4. Animal Models of Psoriasis construction method according to claim 3, which is characterized in that the time of the stimulation is 13
~15d.
5. Animal Models of Psoriasis construction method according to claim 2, which is characterized in that will stimulate and instruct through the empty bottle
Animal after white silk gives Behaviors survey to confirm anxiety state.
6. Animal Models of Psoriasis construction method according to claim 5, which is characterized in that the Behaviors survey includes
Elevated plus-maze and spacious field experiment.
7. Animal Models of Psoriasis construction method according to claim 1, which is characterized in that the imiquimod induction
Method include: daily in be confirmed as anxiety state back part of animal dermal application surface density be 6~8mg/cm2Imiquimod.
8. Animal Models of Psoriasis construction method according to claim 7, which is characterized in that the concentration of the imiquimod
It is 4.5~5.5%；
Preferably, the time of the induction is 13~15d.
9. Animal Models of Psoriasis construction method according to claim 3, which is characterized in that the imiquimod induction
Meanwhile the random empty bottle stimulation is carried out to keep the anxiety state.
10. Animal Models of Psoriasis construction method according to claim 1, which is characterized in that the animal includes rat
And mouse；
Preferably, the animal is mouse.
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| CN110327326A (en) * | 2019-08-12 | 2019-10-15 | 北京市中医研究所 | Isorhamnetin preparation for preventing and treating the drug of psoriasis, the application in health care product |
| CN112136764A (en) * | 2020-09-27 | 2020-12-29 | 澎立生物医药技术（上海）有限公司 | Animal model of psoriasis and construction method and application thereof |
| CN114847235A (en) * | 2022-05-09 | 2022-08-05 | 北京市中医药研究所 | Psoriasis animal model and construction method thereof |
| RU2820279C1 (en) * | 2023-07-21 | 2024-06-03 | Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ онкологии им. Н.Н. Блохина" Минздрава России) | Method for forming experimental model of chronic imiquimod-induced psoriasis-like dermatitis in mice |
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| CN112136764A (en) * | 2020-09-27 | 2020-12-29 | 澎立生物医药技术（上海）有限公司 | Animal model of psoriasis and construction method and application thereof |
| CN114847235A (en) * | 2022-05-09 | 2022-08-05 | 北京市中医药研究所 | Psoriasis animal model and construction method thereof |
| RU2820279C1 (en) * | 2023-07-21 | 2024-06-03 | Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ онкологии им. Н.Н. Блохина" Минздрава России) | Method for forming experimental model of chronic imiquimod-induced psoriasis-like dermatitis in mice |
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