CN102512259A - Novel method for establishing vascular dementia rat model - Google Patents
Novel method for establishing vascular dementia rat model Download PDFInfo
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- CN102512259A CN102512259A CN2011103663046A CN201110366304A CN102512259A CN 102512259 A CN102512259 A CN 102512259A CN 2011103663046 A CN2011103663046 A CN 2011103663046A CN 201110366304 A CN201110366304 A CN 201110366304A CN 102512259 A CN102512259 A CN 102512259A
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Abstract
The invention discloses a novel method for establishing a vascular dementia rat model. According to the novel method, a 6-week old male clean and healthy Sprague Dawley (SD) rat with the weight of 180-220g is subjected to long-term gavage by adopting isocarbophos, wherein the gavage concentration of the isocarbophos is 0.5mg/kg, the gavage capacity is 3ml/kg, the gavage frequency is one time every other day, and the gavage period is 24 weeks. The vascular dementia rat model is established through chronic damage of the isocarbophos to the brain vessels and brain nervous tissues of the SD rat.
Description
Technical field
The present invention relates to a kind of novel method of setting up the vascular dementia rats model; Specifically a kind of employing isocarbophos is irritated stomach for a long time to the SD rat, causes chronic injury to set up the vascular dementia rats model through isocarbophos to SD rat aorta and cerebral nerve tissue.
Background technology
(Vascular Dementia VD) is the dementia syndrome that causes brain tissue damage to cause owing to a series of blood vessel injury factors to VD., cognitive function impaired with memory drops to the master, or is one group of unusual syndrome of mind of main clinical manifestation with language function decline and emotion, personality disorder.
In American-European countries, VD accounts for 15% of senile dementia sum; In Asian countries such as China, Japan, VD accounts for 50% of senile dementia sum.At present, the VD prevalence of China is 3,24/,100,000, and the prevalence of VD is 1.3% among >=65 years old crowd.And along with the sickness rate of aged tendency of population and vascular conditions increases, the sickness rate of VD is in rising trend.Modern medicine study is thought; VD is multifactor injury disease; Its cause of disease possibly comprise hypertension, diabetes, arteriosclerosis, coronary heart disease, cerebral infarction, cerebral ischemia reperfusion injury etc., and its inducement possibly comprise smoking, drinks, environmental pollution, ionizing radiation etc.Regrettably, do not confirm the true cause of VD morbidity up to now as yet, more do not find ideal anti-VD medicine.Therefore, no matter start with, find correct treatment target spot, develop ideal intervention medicine, will contribute ensureing human health and improving the life of elderly person quality from the cause of disease or the inducement of VD!
The foundation of animal model is the pathogenetic essential condition of study of disease.At present; Common VD method for establishing model comprises: the 1. outer blocked method of blood vessel, as four blood vessel blocking methods (four vessel occlusion, 4VO), three blood vessel blocking methods (three vessel occlusion; 3VO), two blood vessel blocking methods (two vessel occlusion, 2VO); 2. vascular peg stay method; 3. middle cerebral artery occlusion model (middle cerebral artery occlusion, MCAO); 4. the spontaneous rat animal model of hypertension apoplexy (stroke-prone spontaneously hypertensive rats, SPSHR); 5. decerebrate cortex VD animal model; 6. stereotaxis photochemical induction cerebral infarction model; 7. intracerebral injection Endothelin method.
Though the method for building up of VD animal model is more; But every kind of method all is to accomplish from some sides of simulating human VD morbidity; Still have necessarily with the clinical practice situation and to depart from; Subject matter have following some: 1. at present the VD model all is to be based upon on the basis of wound, and the toleration of rat own is poor, and traumatic model causes the rats death rate high; 2. the VD cause of disease is complicated, and the influence factor is more, and the morbidity time-histories is longer.And the time of present VD modelling is generally shorter, can not the complete reaction practical situation; 3. wound itself stress have certain influence to the stability of VD model to what body caused.Therefore, it is necessary for the pathogeny of research VD to set up a kind of long-term, chronic non-invasive VD model!
Symptoms such as some social survey data show, long-term, low dosage contact organophosphorus pesticide can cause that memory is impaired, cognition and language function decline, affective disorder.1. Wesseling C carries out spiritual psychological digital coding analysis to the Fructus Musae workman of 157 long term exposure in the organophosphor environment; The result shows that long-term, low dosage contact organophosphorus pesticide causes tangible language function to descend and personality disorder (Wesseling C, Keifer M; Ahlbom A; McConnell R, Moon JD, Rosenstock L; Hogstedt C. Long-term neurobehavioral effects of mild poisonings with organophosphate and n-methyl carbamate pesticides among banana workers. Int J Occup Environ Health, 2002.); 2. Stephens R carries out neuropsychology investigation to the Pilus Caprae seu Ovis workman of 146 long term exposure in the organophosphorus pesticide environment, and the result shows, long-term, low dosage contact organophosphorus pesticide causes tangible impermanent memory power to be undermined language function to descend; And symptom (Stephens R such as cognition, affective disorder appear; Spurgeon A, Calvert IA, Beach J; Levy LS; Berry H, Harrington JM. Neuropsychological effects of long-term exposure to organophosphates in sheep dip. Lancet, 1995.).We guess through above-mentioned investigation, and there is certain cause effect relation in " long-term, low dosage contact organophosphor " with " VD ".So we have carried out zoopery long-term, that low dosage contact isocarbophos brings out SD rat generation VD by laboratory year April in July, 2010-2011.Through acute, the chronic toxicological experiment of isocarbophos to the SD rat, confirm that the filling stomach concentration of isocarbophos is 0.5mg/kg, the filling gastric capacity is 3ml/kg, the next day of irritating the stomach frequency and be 1 time, irritating gastric cycle was 24 weeks.Matched group adopts the 2VO legal system to be equipped with the VD rat model.Adopt the rat step down test, keep away dark test and Morris water maze test (Morris Water Maze; MWM) judge the rat memory function, and learn experiment, blood vessel and cerebral neuron morphology through vascular function and test and judge the whether success of VD rat model.
Summary of the invention
The invention provides a kind of novel method of the VD of foundation rat model.
The invention provides a kind of novel method of the non-invasive VD of foundation rat model.
The invention provides a kind of method of utilizing isocarbophos to irritate stomach and set up the VD rat model.
SD rat provided by the invention is cleaning level, healthy SD rat, and Mus age was 6 ages in week, and sex is male, and the body constitution amount is 180 ~ 220g.
It is 0.5mg/kg that isocarbophos provided by the invention is irritated stomach concentration, and fillings gastric capacity is 3ml/kg, and the next day of irritating the stomach frequency and be 1 time, the filling gastric cycle was 24 weeks.
The isocarbophos that the present invention uses can directly be bought, and dilutes according to actual concentrations.
SD rat growing environment of the present invention requires: the Animal House temperature is 18～22 ℃, and relative humidity is 40～70%, and air velocity is 0.1～0.2 meter per second; Rate of ventilation is 30 times/hour; Environment cleanliness is 10000～100000 grades, and three grades of directed control air pressure reduction are 0～20%, and (08:00～20:00 is an illumination period to automatic timer control periodicity of illumination; 20:00～08:00 is a dark period), conventional rat feed and purified tap water are raised.
The filling stomach method that the present invention adopts is the rat oral gavage method of using always, irritates the stomach pin and inserts the oral cavity through the rat bicker, gently presses rat root of the tongue portion, and rat independently swallows, and operator take advantage of a situation filling stomach pin is sent in the rat stomach, and medicine is pushed.
Through step down test, keep away the VD rat model that dark test, Morris water maze test, vascular function learn VD rat model that experiment and morphology experiment showed, that this method sets up and traditional invasive method preparation and do not have notable difference, explain that model is successful.
Description of drawings
Fig. 1 isocarbophos brings out VD rat model diving tower, (
± s) (compares * P < 0.05 with positive controls to keep away dark test result's incubation period; Compare with the normal control group, # 0.05).Result of the test shows, VD model group rat step down test incubation period and the apparent in view shortening of normal control group are compared there was no significant difference with positive controls; VD model group rat is kept away dark test incubation period and the apparent in view shortening of normal control group, compares there was no significant difference with positive controls.Show that modeling is more satisfactory.
Fig. 2 isocarbophos brings out VD rat model diving tower, (
± s) (compares * P < 0.05 with positive controls to keep away dark experimental mistake number of times result; Compare with the normal control group, # 0.05).Result of the test shows that VD model group rat step down test errors number increases with the normal control group is apparent in view, with positive controls comparison, there was no significant difference; VD model group rat keeps away dark experimental mistake number of times and the normal control group is apparent in view increases, with positive controls relatively, there was no significant difference.Show that modeling is more satisfactory.
Fig. 3 isocarbophos brings out VD rat model common carotid artery endothelium-dependent relaxation stretching reaction, and (endothelium dependence relaxation reaction EDRR) detects raw-data map.
Fig. 4 isocarbophos brings out VD rat model common carotid artery EDRR and detects (
± s).Compare * P < 0.05 with positive controls; Compare with the normal control group, # < 0.05.Compare with the normal control group, VD model group EDRR significant reaction reduces, and vascular endothelial function significantly descends; Compare with positive controls, VD model group EDRR reacts no significant difference.Show that modeling is more satisfactory.
Fig. 5 isocarbophos brings out VD rat model common carotid artery tunica intima light microscopic and electron microscopic observation result, and (the light microscopic photo picks up from Histology and Embryology teaching and research room of Xinxiang College of Medical Science; Electromicroscopic photograph picks up from Xinxiang College of Medical Science's Electron Microscopy Room).Under the light microscopic, obvious splitting traces appears in VD model group common carotid artery tunica intima, and the inner membrance gauffer increases, and lipid has the arteriosclerosis tendency in the endothelium deposit; Obviously fracture, fusion phenomenon appear in smooth muscle layer cell arrangement disorder under the tunica intima, flesh layer, and continuity is relatively poor, proliferation of fibrous tissue between the myocyte; Fibrous connective tissue is loose under the flesh layer, and flesh layer and connective tissue boundary are unclear.Under the Electronic Speculum, fracture phenomena appears in VD model group endothelial cell membrane, and smooth muscle cell extends into the endotheliocyte endochylema; The fracture of endothelium basement membrane, breaks has a large amount of collagenous tissue hypertrophy; Golgi body increases in the endotheliocyte, and mitochondrial swelling, mitochondrial crista merge or disappearance.
Fig. 6 isocarbophos brings out VD rat model Hippocampus CA1 district's cortex light microscopic and electron microscopic observation result, and (the light microscopic photo picks up from Histology and Embryology teaching and research room of Xinxiang College of Medical Science; Electromicroscopic photograph picks up from Xinxiang College of Medical Science's Electron Microscopy Room).Under the light microscopic, the three layers of pyramidal cell arrangement disorder in VD model group Hippocampus CA1 district; The swelling of part pyramidal cell, and cell infiltration is arranged, the astrocyte hypertrophy; Part pyramidal cell cell space diminishes or is triangular in shape, and apical dendrite prolongs, and karyopycnosis and fracture phenomena are arranged, and endochylema is evenly has a liking for Yihong color; Part pyramidal cell karyon shoals, and the tangible microvoid bubble of the loose companion of substrate forms; There is erythrocyte to ooze out around the blood vessel, still visible little blood vessel hyperplasia.Under the Electronic Speculum, VD model blood brain barrier inner membrance is rough; Neuronal cell shrinkage, membrane structure are unclear; The karyon pyknosis, chromatin agregation is agglomerating, the limit collection, and heterochromatin increases, nuclear Zhou Kejian high electron density agglomerate; Golgi body increases, mitochondrial swelling, and mitochondrial crista merges and the formation of vacuoles degeneration.
The specific embodiment
Embodiment is used to explain the present invention, but does not limit the scope of the invention.Rat body constitution amount is 200g, and isocarbophos concentration is 20%.According to irritating stomach concentration is that 0.5mg/kg calculates, and this rat needs isocarbophos 0.1mg.The isocarbophos 0.5ml of pipette, extract 20% moves in the graduated cylinder, is the solution that contains the 0.1mg isocarbophos.Irritate gastric capacity and require (3ml/kg * 0.2kg) for 0.6ml.Therefore, in graduated cylinder, add distilled water, after filling stomach pin is all drawn, the SD rat is irritated stomach to 0.6ml.
Experimental example:Detect the isocarbophos administration by gavage and set up the feasibility of VD model.
1, medicine: isocarbophos (LS93564,20%, the Hubei sand swell reaches limited company).
2, purpose: utilize isocarbophos that the SD rat is irritated 24 weeks of stomach and set up the VD model.
3, instrument: rat diving tower recording system, rat are kept away dark appearance, Morris water maze (Huaibei Zhenghua Biological Instrument Co., Ltd.); MD3000 bio signal acquisition system (Huaibei Zhenghua Biological Instrument Co., Ltd.); TS1000 Nikon microscope (Japanese Nikon company); HT7700 Hitachi transmitted electron shows (HIT).
4, animal: 6 ages in week, male, 180 ~ 220g, cleaning level, healthy SD rat (Henan Province's Experimental Animal Center).
5, experiment is divided into groups: 1. normal control group: 10 of 6 ages in week, male, 180 ~ 220g, cleaning level, healthy SD rat, the conventional raising for 24 weeks; 2. VD model group: 10 of 6 ages in week, male, 180 ~ 220g, cleaning level, healthy SD rat they are carried out isocarbophos irritate stomach, irritating stomach concentration is 0.5mg/kg, and fillings gastric capacity is 3ml/kg, and the next day of irritating the stomach frequency and be 1 time, the filling gastric cycle was 24 weeks; 3. positive controls: 10 of 6 ages in week, male, 180 ~ 220g, cleaning level, healthy SD rat, adopt 2VO to prepare rat VD model.12h fasting before the art, 4h prohibits water.With 10% chloral hydrate (0.33ml/100g) intraperitoneal injection of anesthesia, guarantee that intra-operative has autonomous respiration.It is fixing to lie on the back, and cervical region QUMAO, Iodophors sterilization tailing edge neck medisection is isolated bilateral common carotid arteries, and cover is with dual " 0 " number line, in the proximal part and the distal end ligation respectively of bilateral common carotid arteries, and from the centre from disconnected, to guarantee the interruption artery blood flow.Note sterile working in the art, operative incision gives injection liquid of gentamicin 2 ml, sews up the incision.Postoperative is delivered to draughty Animal House with animal and is raised; 4. negative control group: 10 of 16 ages in week, male, 180 ~ 220g, cleaning level, healthy SD rat, 12h fasting before the art, 4h prohibits water.With 10% chloral hydrate (0.33ml/ 100g) intraperitoneal injection of anesthesia, guarantee that intra-operative has autonomous respiration.Only separate bilateral common carotid arteries behind the rat anesthesia, but not ligation, from disconnected tremulous pulse.
6, experiment content: rat step down test, rat are kept away dark test, rat Morris water maze test, EDRR detection, rat carotid artery inner membrance light microscopic and electron microscopic observation, rat brain Hippocampus CA1 district's cortex light microscopic and electron microscopic observation.
7, statistical method: all data are with (
± s) expression of mean ± standard deviation.Group difference is relatively with ANOVA and Newman-Student multiple comparisons; The t check analysis is accomplished by the SPSS13.0 statistical software, and bilateral P＜0.05 thinks that difference has significance.
8, result
8.1 isocarbophos brings out VD rat model step down test
The result sees table 1.VD model group rat step down test incubation period and the apparent in view shortening of normal control group are compared there was no significant difference with positive controls; Average 5 minutes errors number of VD model group rat and the normal control group is apparent in view increases, with positive controls relatively, there was no significant difference.Show that modeling is more satisfactory.
Table 1 isocarbophos brings out VD rat model step down test result (
± s)
| Divide into groups | n | Incubation period (second) | Errors number/5 minute (inferior) |
| The normal control group | 10 | 169.58±36.29 * | 0.29±0.09 * |
| The VD model group | 10 | 54.26±20.25 # | 2.85±1.65 # |
| Positive controls | 10 | 59.28±22.69 # | 2.91±1.23 # |
| Negative control group | 10 | 159.98±42.65 * | 0.26±0.08 * |
Annotate: compare * P < 0.05 with positive controls; Compare with the normal control group, # < 0.05.
8.2 bringing out the VD rat model, isocarbophos keeps away dark test
The result sees table 2.VD model group rat is kept away dark test incubation period and the apparent in view shortening of normal control group, compares there was no significant difference with positive controls; Average 5 minutes errors number of VD model group rat and the normal control group is apparent in view increases, with positive controls relatively, there was no significant difference.Show that modeling is more satisfactory.
Table 2 isocarbophos brings out the VD rat model and keeps away dark result of the test (
± s)
| Divide into groups | n | Incubation period (second) | Errors number/5 minute (inferior) |
| The normal control group | 10 | 184.54±39.09 * | 0.43±0.12 * |
| The VD model group | 10 | 26.68±15.76 # | 3.54±1.65 # |
| Positive controls | 10 | 24.87±11.32 # | 3.65±1.73 # |
| Negative control group | 10 | 176.87±48.67 * | 0.41±0.18 * |
Annotate: compare * P < 0.05 with positive controls; Compare with the normal control group, # < 0.05.
8.3 isocarbophos brings out VD rat model diving tower, keeps away dark test result's incubation period
The result sees Fig. 1.Result of the test shows, VD model group rat step down test incubation period and the apparent in view shortening of normal control group are compared there was no significant difference with positive controls; VD model group rat is kept away dark test incubation period and the apparent in view shortening of normal control group, compares there was no significant difference with positive controls.Show that modeling is more satisfactory.
8.4 isocarbophos brings out VD rat model diving tower, keeps away dark experimental mistake number of times result
The result sees Fig. 2.Result of the test shows that VD model group rat step down test errors number increases with the normal control group is apparent in view, with positive controls comparison, there was no significant difference; VD model group rat keeps away dark experimental mistake number of times and the normal control group is apparent in view increases, with positive controls relatively, there was no significant difference.Show that modeling is more satisfactory.
8.5 isocarbophos brings out VD rat model Morris water maze test
The result sees table 3.1. the orientation navigation result of the test shows, the platform search time of VD model group obviously prolongs, with the positive controls no significant difference; 2. space exploration test shows, swimming distance (rice) shortens in the platform quadrant of VD model group, the swimming distance is dwindled with the ratio of total swimming distance in platform quadrant distance (rice) zero difference of swimming outward that distance (rice) prolongs, all quadrants is always swum, platform quadrant, swimming time (second) shortens in the platform quadrant, outer swimming time (second) prolongation of platform quadrant, the interior swimming time of platform quadrant are dwindled with the ratio of total time, in the quadrant on average swimming rate (meter per second) zero difference, quadrant outward on average swimming rate (meter per second) zero difference, the average swimming rate of all quadrants (meter per second) zero difference, pass through the minimizing of platform number of times; Compare VD model group index zero difference with positive controls.The result shows that modeling is more satisfactory.
Table 3 isocarbophos brings out VD rat model Morris water maze test result (
± s)
| Index | The normal control group | The VD model group | Positive controls | Negative control group |
| Swimming distance in the quadrant | 2.26±0.64 * | 1.29±0.35 # | 1.35±0.42 # | 2.45±0.58 * |
| The quadrant distance of swimming outward | 2.19±0.54 * | 2.86±0.68 # | 2.95±0.98 # | 2.09±0.61 * |
| The all quadrants distance of always swimming | 4.21±0.87 | 4.32±0.99 | 4.09±1.01 | 4.23±1.21 |
| In the quadrant swimming distance and total swimming apart from than | 0.45±0.12 * | 0.35±0.08 # | 0.32±0.09 # | 0.48±0.17 * |
| Swimming time in the quadrant | 30.26±4.98 * | 19.58±3.21 # | 18.25±4.69 # | 31.26±6.39 * |
| The outer swimming time of quadrant | 29.65±4.09 * | 41.68±6.43 # | 43.33±7.26 # | 28.78±5.69 * |
| Swimming time and total useful time ratio in the quadrant | 1.07±0.11 * | 0.59±0.08 # | 0.52±0.06 # | 1.13±0.09 * |
| Average swimming rate in the quadrant | 67.89±9.87 | 65.29±8.12 | 67.48±11.98 | 69.29±10.23 |
| The outer average swimming rate of quadrant | 69.26±8.43 | 67.29±12.54 | 69.45±10.28 | 68.44±9.77 |
| The average swimming rate of all quadrants | 68.73±8.59 | 66.39±8.57 | 69.84±7.12 | 68.98±6.91 |
| Through the platform number of times | 6.7±2.14 * | 3.5±0.69 # | 3.6±0.89 # | 6.9±2.11 * |
Annotate: compare * P < 0.05 with positive controls; Compare with the normal control group, # < 0.05.
8.6 bringing out VD rat model common carotid artery EDRR, isocarbophos detects
The result sees Fig. 3,4.Compare with the normal control group, VD model group EDRR significant reaction reduces, and vascular endothelial function significantly descends; Compare with positive controls, VD model group EDRR reacts no significant difference.Show that modeling is more satisfactory.
8.7 isocarbophos brings out VD rat model common carotid artery tunica intima light microscopic and electron microscopic observation result
The result sees Fig. 5.Under the light microscopic, obvious splitting traces appears in VD model group common carotid artery tunica intima, and the inner membrance gauffer increases, and lipid has the arteriosclerosis tendency in the endothelium deposit; Obviously fracture, fusion phenomenon appear in smooth muscle layer cell arrangement disorder under the tunica intima, flesh layer, and continuity is relatively poor, proliferation of fibrous tissue between the myocyte; Fibrous connective tissue is loose under the flesh layer, and flesh layer and connective tissue boundary are unclear.Under the Electronic Speculum, fracture phenomena appears in VD model group endothelial cell membrane, and smooth muscle cell extends into the endotheliocyte endochylema; The fracture of endothelium basement membrane, breaks has a large amount of collagenous tissue hypertrophy; Golgi body increases in the endotheliocyte, and mitochondrial swelling, mitochondrial crista merge or disappearance.
8.8 isocarbophos brings out VD rat model Hippocampus CA1 district's cortex light microscopic and electron microscopic observation result
The result sees Fig. 6.Under the light microscopic, the three layers of pyramidal cell arrangement disorder in VD model group Hippocampus CA1 district; The swelling of part pyramidal cell, and cell infiltration is arranged, the astrocyte hypertrophy; Part pyramidal cell cell space diminishes or is triangular in shape, and apical dendrite prolongs, and karyopycnosis and fracture phenomena are arranged, and endochylema is evenly has a liking for Yihong color; Part pyramidal cell karyon shoals, and the tangible microvoid bubble of the loose companion of substrate forms; There is erythrocyte to ooze out around the blood vessel, still visible little blood vessel hyperplasia.Under the Electronic Speculum, VD model blood brain barrier inner membrance is rough; Neuronal cell shrinkage, membrane structure are unclear; The karyon pyknosis, chromatin agregation is agglomerating, the limit collection, and heterochromatin increases, nuclear Zhou Kejian high electron density agglomerate; Golgi body increases, mitochondrial swelling, and mitochondrial crista merges and the formation of vacuoles degeneration.
Claims (5)
1. novel method of setting up the vascular dementia rats model.
2. rat according to claim 1 is characterized in that cleaning level, healthy SD rat, and Mus age was 6 ages in week, and sex is male, and the body constitution amount is 180 ~ 220g.
3. novel method according to claim 1 is characterized in that adopting isocarbophos that the SD rat is irritated stomach for a long time.
4. filling stomach according to claim 3, it is characterized in that irritating gastric capacity is 3ml/kg, irritating stomach concentration is 0.5mg/kg, the next day of irritating the stomach frequency and be 1 time.
5. according to claim 3 long-term, it is characterized in that irritating gastric cycle was 24 weeks.
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| CN104968197A (en) * | 2013-02-06 | 2015-10-07 | 伊诺特纳皮株式会社 | Animal model for evaluating performance of hemostatic agent for inducing hemorrhage in common carotid artery or superior sagittal sinus, and use thereof |
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|---|---|---|---|---|
| CN1545868A (en) * | 2003-12-17 | 2004-11-17 | 暨南大学 | Preparing method for Alzheimer disease animal model |
| JP2008193941A (en) * | 2007-02-13 | 2008-08-28 | Japan Health Science Foundation | Vascular dementia model mouse and method for preparing the same |
| CN101284138A (en) * | 2008-06-04 | 2008-10-15 | 刘铁军 | Preparation method of chronic liver injury unit stress depression rat model |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1545868A (en) * | 2003-12-17 | 2004-11-17 | 暨南大学 | Preparing method for Alzheimer disease animal model |
| JP2008193941A (en) * | 2007-02-13 | 2008-08-28 | Japan Health Science Foundation | Vascular dementia model mouse and method for preparing the same |
| CN101284138A (en) * | 2008-06-04 | 2008-10-15 | 刘铁军 | Preparation method of chronic liver injury unit stress depression rat model |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104968197A (en) * | 2013-02-06 | 2015-10-07 | 伊诺特纳皮株式会社 | Animal model for evaluating performance of hemostatic agent for inducing hemorrhage in common carotid artery or superior sagittal sinus, and use thereof |
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Application publication date: 20120627 |