CN115192710A - Application of miRNA-200s protective agent in preparation of nervous system disease drugs, drugs and model construction method - Google Patents
Application of miRNA-200s protective agent in preparation of nervous system disease drugs, drugs and model construction method Download PDFInfo
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Abstract
The invention discloses application of a miRNA-200s protective agent in preparation of nervous system disease medicines, a medicine and a model construction method, and relates to the field of biological medicines. The nervous system disease medicine is prepared by miRNA-200s protective agent (Gene Bio); the construction method for verifying the protective agent model of the nervous system disease comprises the following steps: injecting the nervous system disease drugs into mice after the model of the nervous system disease. The research of the invention finds that the miRNA-200s protective agent can be used for preparing medicines for treating nervous system diseases, so that the nervous system diseases including demyelination, neuron damage, optic neuritis and the like can be improved. The method has high treatment sensitivity and remarkable improvement effect. The invention has good application value and popularization prospect.
Description
Technical Field
The invention relates to the field of parasite and nerve injury protection, in particular to application of a miRNA-200s protective agent in preparation of medicines for treating nervous system diseases, a medicine and a model construction method.
Background
MicroRNAs (miRNAs) are endogenous, 18,22 nucleotide, non-coding RNA molecules that act as post-transcriptional regulators of gene expression. mirnas specifically bind to mRNA of the 3-untranslated region (3-UTR) through complete or incomplete complementarity, inducing translational inhibition or RNA degradation in cells. miRNA disorders have also been found in demyelinating diseases of the central nervous system (e.g., multiple sclerosis), cancer, neurodegenerative diseases such as alzheimer's disease, parkinson's disease, huntington's disease, amyotrophic lateral sclerosis, neurological diseases such as epilepsy, and the like.
CNS demyelinating diseases are clinically common diseases, and mainly include Multiple Sclerosis (MS), acute Disseminated Encephalomyelitis (ADEM), neuromyelitis optica (NMO), and the like. It has been found that demyelinating diseases can be caused by Alzheimer's Disease (AD), neuropsychiatric diseases such as systemic lupus erythematosus and schizophrenia, and stress factors such as stress, and that myelin sheath damage can be directly caused by infection with various pathogenic microorganisms such as Angiostrongylus cantonensis (a. Cantonensis) and autoimmune, genetic and environmental factors, bacteria, viruses or parasites. The clinical manifestations of demyelinating diseases are mainly impaired movement, sensory disturbance and cognitive function, visual impairment can occur to those who involve optic nerve, and the disease conditions are complicated or sequela remains, which seriously affects the quality of life of patients. At present, the treatment of myelin sheath damage diseases is mainly symptomatic treatment, including nonspecific immunoregulation treatment, humanized monoclonal antibodies, drugs with neuroprotective effect and the like, and the treatment effect is limited. Therefore, it is the focus of the current CNS demyelination disease to explore the pathogenesis of CNS demyelination, and to find more effective and safe drugs to inhibit the progression of myelin damage and promote myelin repair and regeneration.
Neuronal degeneration and death are important markers of neurodegenerative diseases. Some recently published studies have demonstrated the importance of mirnas in the nervous system and are contributing to increasing evidence that mirnas are disregulated in neurological diseases. Understanding the expression and activity of these mirnas may be helpful in the development of new therapies. During normal development of the nervous system, a large number of neuronal apoptosis occurs, precisely matching the neurons to their respective target cells. However, once the appropriate neurons are connected in place, they must strictly inhibit their apoptotic program, as these cells do not divide, have limited regenerative capacity, and must survive the life cycle of the body. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Here, we investigated whether mirnas serve as key survival regulators in mature neurons, and the significance of miRNA deregulation in the development of neurodegenerative diseases, and the use of mirnas as targets for therapeutic intervention.
Optic neuritis (optic neuritis) is a general term for inflammation at any part of the optic nerve, and broadly refers to diseases such as inflammatory demyelination, infection, and nonspecific inflammation of the optic nerve. Clinically, optic neuritis is classified into intrabulbar and retrobulbar types according to the disease site of lesion lesions, the former refers to optic disc inflammation, and the latter refers to retrobulbar optic neuritis. Optic neuritis is mostly unilateral, optic papillitis is often seen in children, and retrobulbar optic neuritis is often seen in young and strong years. Ganglion cells are the most important neurons in the retina, whose axons form the optic nerve. Damage to ganglion cells can cause severe visual impairment. It is well known that in the rat model of optic neurosurgical axial dissection 80-90% of retinal ganglion cells undergo apoptotic cell death after optic nerve dissection. In experimental optic neuritis, inflammatory demyelination induces axonal damage and apoptosis of retinal ganglion cells. The related literature reports that the BDA retrograde labeling result indicates that part of ganglion cells are lost and the optic nerve is demyelinated to a certain degree, thereby providing evidence for the occurrence of optic neuritis. Therefore, it is important to study the pathogenesis of optic neuritis and find more effective and safe drugs to improve optic nerve damage.
The application relates to application of a miRNA-200s protective agent in preparation of medicines for nervous system diseases, medicines and a model construction method, so that the nervous system diseases including demyelination, neuronal damage, optic neuritis and the like are improved.
Disclosure of Invention
The invention aims to provide an application of a miRNA-200s protective agent in preparation of medicines for nervous system diseases, a medicine and a model construction method.
The first purpose of the invention is the application of miRNA-200s protective agent in preparing medicines for nervous system diseases.
The second purpose of the invention is that the miRNA-200s protective agent can be used for preparing medicines for treating nervous system diseases, thereby improving the nervous system diseases including demyelination, neuron damage, optic neuritis and the like.
The third purpose of the invention is the application of the miRNA-200s protective agent in the preparation of the medicines for treating nervous system diseases, wherein the nervous system diseases comprise various central nervous system diseases caused by angiostrongylus cantonensis infection.
In order to realize the purpose, the invention is realized by the following technical scheme:
application of miRNA-200s protective agent in preparation of medicines for treating nervous system diseases.
Further, the neurological disease is manifested by damage to oligodendrocytes, neuronal cells, retinal ganglion cells and infiltration of inflammatory cells.
Further, the nervous system disease is one of demyelination of the central nervous system, neuronal damage, optic neuritis.
Furthermore, the miRNA-200s protective agent is applied in a dosage of 1nmol/20g of body weight, the application objects are Balb/c mice and other central nerve injured animals, the application route is intracranial stereotactic injection or intravenous injection, and the treatment method is quick, concise, reasonable and effective. The dosage of the therapeutic target miRNA-200s is 1nmol/20g of body weight, the drug objects are Balb/c mice and other central nerve injury animals, and the drug application route is intracranial stereotaxic injection or intravenous injection.
Further, the nervous system diseases include, but are not limited to, various central nervous system diseases caused by angiostrongylus cantonensis infection.
A medicine for treating nervous system diseases comprises a miRNA marker related to nervous system injury protection, wherein the miRNA marker comprises miRNA-200a-3p, miRNA-200b-5p, miRNA-200c-3p, miRNA-429-3p, miRNA-141-5p, preferably, the miRNA-200a-3p and miRNA-200c-3p play the most obvious protective effect after combined over-expression.
A medicament for treating nervous system diseases comprises a miRNA marker related to nervous system injury protection, wherein the gene sequence of the miRNA marker is (5 'to 3') mmu-miR-200a-3P-F TAACACTGTCTGGTAACGATGT; mmu-miR-200b-5P-F CATCTTTACTGGGCAGCATTGGA; mmu-miR-200c-3P-F TAATACTGCCGGGTAATGATGGA; mmu-miR-429-3P-F TAATACTGTCTGGTAATGCCGT; mmu-miR-141-5P-F CATCTTCTCCAGTGCAGTTGGGA.
A method for constructing a drug verification model for nervous system diseases comprises the following steps: the medicament for treating the nervous system diseases is injected into mice after the model of the nervous system diseases is made, is safe and effective to model animals, and has no obvious side effect and complication.
Preferably, the treatment subjects of the treatment method include but are not limited to Balb/c mice and other animals, and the clinical case is also applicable to patients.
A construction method of a disease drug verification model specifically comprises the following steps:
1) Selecting a mouse to carry out model building of nervous system diseases;
2) After molding, injecting the nervous system disease drug into the mice;
3) Then, the damage condition and the brain damage degree of the oligodendrocyte, the neuron cell and the retinal ganglion cell of the mouse are detected.
In the above method, the detection method is immunofluorescence, magnetic resonance imaging technique and/or LFB staining.
According to the invention, models of central nervous system demyelination injury, neuron injury and optic neuritis caused by Balb/c mice infected by angiostrongylus cantonensis are established, and miRNA-200s infection is obviously up-regulated in the early stage and reduced in the later stage through a microRNA chip technology and RT-qPCR quantitative analysis. Selecting exogenous over-expressed miRNA-200s, identifying and analyzing by using techniques such as western blot, RT-qPCR, H & E staining, LFB staining, transmission electron microscopy, immunofluorescence and the like, and judging that the miRNA-200s is a treatment target of the injury model; the miRNA-200s protective agent is used for preparing medicines for treating nervous system diseases to improve neurobehavioral fates, pathological symptoms and physical signs of infected mice, so that the protective effect on central nervous system demyelinating injury, neuron injury and optic neuritis caused by infection is exerted, and a novel treatment method is provided.
Therefore, the invention claims the application of the miRNA-200s protective agent in the preparation of medicines for treating nervous system diseases.
The application of the miRNA-200s protective agent in preparing the nervous system disease medicine in improving angiostrongylus cantonensis also belongs to the protection scope of the invention.
A miRNA-200s protective agent can be used for preparing medicines for treating nervous system diseases, such as demyelination, neuron injury and optic neuritis. And is safe and effective for model animals without obvious side effects and complications.
A method for constructing a model for drug verification of nervous system diseases, which comprises the steps of: injecting the nervous system disease medicament into the mice after the molding of the nervous system disease.
Most preferably, the miRNA-200s protective agent is used for preparing the medicines for treating the nervous system diseases, wherein the nervous system diseases are one of central nervous system demyelination, neuron damage and optic neuritis.
The treatment method comprises the following steps:
1. establishing a central nervous system demyelination injury, optic nerve injury and neuron injury model of the Balb/c mouse.
2. A medicine prepared by exogenously over-expressing miRNA-200s protective agent.
The medicine prepared from the miRNA-200s protective agent is injected into the lateral ventricle of the animal with central nervous system injury through stereotaxic injection or intravenous injection.
3. Analyzing each index:
MRI detection of cerebral cortex, corpus callosum, hippocampus and visual cortex damage; visual change of the injured animal is detected through visual electrophysiology and the like; assessing central nervous system injury changes of the injured animals by neurobehavioral scoring, motor balance ability, learning and memory function and the like; neuropathological tests have demonstrated pathological changes in central nervous system damage such as demyelination, neuronal damage and optic neuritis. After the miRNA-200s are over-expressed, the phenomenon can be partially reversed, and the damage of the nervous system is improved.
Compared with the prior art, the invention has the following beneficial effects:
the invention discloses application of a miRNA-200s protective agent in preparation of medicines for treating nervous system diseases, a medicine and a model construction method, and relates to the field of biological medicines. The nervous system disease medicine is prepared by miRNA-200s protective agent (Gene Bio); the construction method for verifying the protective agent model of the nervous system disease comprises the following steps: injecting the nervous system disease drugs into the mice after the model of the nervous system disease. The research of the invention finds that the miRNA-200s protective agent can be used for preparing medicines for treating nervous system diseases, so that the nervous system diseases including demyelination, neuron damage, optic neuritis and the like can be improved. The method has high treatment sensitivity and remarkable improvement effect. The invention has good application value and popularization prospect.
Drawings
FIG. 1 is the nervous system score and body weight of BALB/c mice with damaged central nervous system.
FIG. 2 shows lesions in mouse calluses after 21 days of infection by MRI and TEM analysis.
FIG. 3 shows the pathology and transmission electron microscopy analysis of the brain tissue of mice with damaged nervous system and over-expressed miRNA-200 s.
FIG. 4 shows the changes of callose oligodendrocytes and neurons before and after miRNA-200s treatment in mice with damaged nervous system.
FIG. 5 shows the pathology of retina and transmission electron microscopy analysis before and after miRNA-200s treatment in mice with damaged nervous system, and the corresponding visual evoked potential analysis and protein quantification analysis of retinal ganglion cells.
FIG. 6 shows the application of miRNA-200s protective agent in preparing nervous system disease drugs, the drugs and the involved nervous system disease model construction method.
Detailed Description
The invention is described in further detail below with reference to the drawings and specific examples, which are provided for illustration only and are not intended to limit the scope of the invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
Example 1 neuro-behavioral changes in infected mice
1. Test method
Starting on day 0 of infection, the body mass of the mice was recorded every 7d and the mice were neuro-behaviorally scored. Neuro-behavioral scoring scale was performed using the method reported by Parra [60 ]. The scoring scale comprises: (1) The motor function comprises 4 experiments of 5min open field, limb symmetry (tail lifting experiment), climbing and balancing rod, and the scoring dimension is 0-3 points. (1) Sensory function, including proprioception (neck-touch), palpitations, vision, smell and touch 5 experiments, with a score of 1-3. The higher the total score, the better the mouse status. See appendix table 1.
2. Test results
As shown in figure 1, the average of the miR-200a and miR-200c water levels of the angiostrongylus cantonensis infected group and the NC control group is obviously lower than that of the normal group, and the expression levels of the miR-200a and miR-200c of the overexpression groups are respectively more than 20 times and 40 times of those of the normal group, so that the expression levels are obviously increased, and the successful overexpression of miR-200s is indicated.
After angiostrongylus cantonensis infection, mice 21d are cachectic, hair is lusterless and upright, the spine is extremely arched, the tail tension is reduced, four limbs are paralyzed in different degrees, part of the limbs have eye infection symptoms, and eyeballs are atrophied, which is mostly unilateral. The total neurological score of the mice in the infected group is 17.3 +/-3.1, the total neurological score of the mice in the agomir control group is 16.2 +/-5.1, and the total neurological score is obviously lower than that of the mice in the normal group by 29.3 +/-0.5. The score of the group acomir-200a and 200c is 24.8 +/-1.0, which is obviously higher than that of the group infected with 21d and the group acomir control. The infection 21d group, the plus agomir-NC group and the agomir-200a &200c group were all significantly lower than the normal group in terms of physical quality. After the miRNA-200s are over-expressed, the symptoms of hemiplegia, limb weakness and the like of the mouse are improved, the blinding rate is obviously reduced, and the symptoms of eyeball infection and atrophy are improved.
Example 2 pathological changes in mice calluses after 21 days of infection
1. Normal mouse imaging
Normal mouse brain MRI coronary position T1WI, T2WI clearly show the space under the dura mater, the corpus callosum structure is clear, the signal is grey, lower than cortex signal.
2. Test results
After 21d infection of angiostrongylus cantonensis, the mouse brains T1WI and T2WI both show a ring of white high signals (shown in the third graph of the second row in figure 2) surrounding the surface of the brain parenchyma, and the white high signals are subdural effusion with the area of 3.1 +/-2.6 mm2; the injured corpus callosum has a signal substantially consistent with the cortex in T1WI, and shows a strong white signal in T2WI (shown in the second panel of the second row in FIG. 2), and the percentage of the injured area in the whole brain is 3.0 + -0.55. Compared with the infection group, the agamir control group has no difference in the effusion area and the callus injury area, the effusion area is still 4.4 +/-1.7mm2 and 2.2 +/-1.9mm2 agamir-200a and 200c, and the effusion volume is not statistically different (3.7 +/-0.6mm2) compared with the infection group; the callus signals in T1WI were similar to those in the normal group, the lesion area was significantly reduced to 0.4 + -0.26mm2, and the difference was statistically significant (P < 0.05), as shown in the lower bar chart of FIG. 2. The ultrastructure of a transmission electron microscope shows that the normal mouse callus has the regular arrangement of the medullary fibers and the uniform thickness of the myelin sheath, while the infected mouse callus has the medullary axons with obviously reduced quantity, so that a large number of abnormal myelin sheath structures can be seen.
Example 3 MiRNA-200s relief of CNS myelin damage, optic nerve damage due to infection
1. Test method
Anesthetizing mouse with 1% sodium pentobarbital at weight of 50mg/Kg, perfusing normal saline through apex of heart, collecting brain, fixing in 4% paraformaldehyde solution for 24 hr, dehydrating, transparentizing, infiltrating, embedding, making into wax block, and cutting into 5 μm thick slices. Pathological changes were observed by H & E staining and myelin lesions were observed by Luxol Fast Blue staining.
Observing brain tissue structure with transmission electron microscope, transecting brain tissue at-20 deg.C into 15 μm slices, and placing on glass slide. The callus was rapidly dissected and fixed with 2.5% glutaraldehyde. Calluses were cut out locally and fixed in a solution containing 1% osmium tetroxide, and then dehydrated with acetone at various concentrations. The dehydrated samples were embedded in SPIN-PON resin and polymerized at 60 ℃ for 3 days. Half-thin sections (0.5 μm thick) were mounted on a glass slide and stained with toluidine blue. Finally, the corpus callosum was observed under a 300KV transmission electron microscope. 3 grids were collected per sample, and 10 photographs were collected per grid. Myelin thickness and axon diameter were measured with ImageJ software and the ratio was calculated as the axon diameter divided by the nerve bundle diameter.
2. Test results
LFB staining of mouse brain shows that the calluses of Guangzhou angiostrongylus infection groups are broken, myelin is lightly stained, and flaky myelin sheath loss areas can be seen. The corpus callosum of the agomir-200a &c administration group is structurally intact, and no obvious demyelination change is seen. H & E results staining showed massive hemorrhage of the corpus callosum of mice in the infected group, and no or light hemorrhage of the corpus callosum in the agomir-200a &c administration group.
The ultrastructure of a transmission electron microscope shows that the normal mouse callus has marrow fibers arranged regularly and has uniform myelin thickness, the average value of g-ratio is 0.75, the diameter of axons is distributed in a centralized way at 0.6-0.8 μm, the average value is 0.68 μm, and the percentage of myelinated axons is 84.6%. The number of myelinated axons in the calluses of mice in the Guangzhou angiostrongylus infection group and the administration control group is obviously reduced (55.6 percent and 60.5 percent), and the g-ratio mean value is reduced (0.69 and 0.66); the decrease in average axon diameter (0.6 μm and 0.57 μm) due to the increase in the number ratio of small-diameter axons; in addition, a number of abnormal myelin structures were visible, including abnormal hyperplasia (yellow triangles), and fragments of myelin (red triangles). And the proportion of the medullary axons in the callus of the agomir-200a &c administration group is 82%, the average value of the diameter of the axons is 0.62um, and the proportion of the medullary axons is not different from the diameter distribution of the axons and the normal group. Notably, thickened myelin was also seen in the agomir-200a &c administration group, with a g-ratio mean of 0.71, which is smaller than that of the normal group (shown in FIG. 3). Similarly, immunohistochemistry and electron microscopy suggest that inflammatory cells infiltrate the optic nerve and retinal region, retinal Ganglion Cells (RGCs) are lost, visual Evoked Potential (VEP) detection shows that latency is prolonged and amplitude is reduced, suggesting possible optic neuritis, and RGCs counting also indicates retinal ganglion cell loss.
Example 4 miRNA-200s contribute to survival of oligodendrocytes, retinal ganglion cells and neurons in infected mice
1. Test method
After the brain sections of the mice were prepared, the cells were stained by immunofluorescence, and observed and photographed under a fluorescence microscope. Taking brain tissue as a frozen section, drawing a hydrophobic region along the boundary of the tissue by using an immunohistochemical pen, fixing the hydrophobic region for 20min by using 4% paraformaldehyde, washing the hydrophobic region for three times by using PBS (phosphate buffer solution), sealing the sealing solution at room temperature for 1 hour, incubating primary antibody and secondary antibody according to a conventional method, finally sealing the sealing solution by using a sealing agent containing DAPI (deoxyribose nucleic acid) and performing immunofluorescence photography under a microscope.
Western blot detects protein quantitative change, and the protein quantitative change is subjected to a series of conventional steps of glue preparation, sample loading, electrophoresis, electrotransformation, sealing, primary antibody incubation, secondary antibody incubation, development and the like, and finally developed and imaged in a chemiluminescence development system.
2. Test results
Results as shown in fig. 4, to detect the change in the number of mouse brain oligodendrocytes following angiostrongylus cantonensis infection, we labeled mature oligodendrocytes with CC-1 and performed a counting analysis of the mature oligodendrocytes at the corpus callosum. The results showed that the number of CC-1+ cells per mm2 in the normal group mice was 568.8. + -. 18.8, and the number of angiostrongylus cantonensis-infected group and the administration control group were reduced to 412. + -. 8.9 and 414. + -. 16.7 (P < 0.0001). Compared with the infected group, the number of the agomir-200a &c administration group was 481 + -17.1, which was significantly increased (P < 0.05). The results show that angiostrongylus cantonensis infects and damages mature oligodendrocyte of mouse CNS and causes the reduction of the quantity of the oligodendrocyte, and the overexpression of miR-200s can reduce the oligodendrocyte damage caused by the angiostrongylus cantonensis infection and is beneficial to the survival of the oligodendrocyte (a bar chart shown in figure 4).
The experimental result also shows that the miR-200s is abundantly expressed in the neuron when the angiostrongylus cantonensis is infected for two days. After miR-200s overexpression, the number of neurons in the hypothalamus was significantly increased compared to non-overexpression (B in FIG. 5).
Visual Evoked Potential (VEP) measurements revealed prolonged latency and reduced amplitude, suggesting possible optic neuritis (C, D, F in FIG. 5). The RGCs counted by Western Blot also indicate the loss of retinal ganglion cells (F and G in figure 5), and the phenomenon of optic nerve damage is improved after miRNA-200s are over-expressed. The expression of the neuron marker NeurN in an infected group is obviously reduced compared with that in a normal group shown by an immunofluorescence chart, and the expression of the NeurN is obviously improved after miRNA-200s is over-expressed compared with that in the infected group.
Appendix 1 mouse neuroethology score Scale [60]
The above-mentioned embodiments are provided to further explain the objects, technical solutions and advantages of the present invention in detail, and it should be understood that the above-mentioned embodiments are only examples of the present invention and are not intended to limit the scope of the present invention. It should be understood that any modifications, equivalents, improvements and the like, which come within the spirit and principle of the invention, may occur to those skilled in the art and are intended to be included within the scope of the invention.
Sequence listing
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Claims (10)
- Application of miRNA-200s protective agent in preparation of medicines for treating nervous system diseases.
- 2. The use of the miRNA-200s protective agent of claim 1, in the preparation of a medicament for the treatment of a neurological condition characterized by the presence of damage to oligodendrocytes, neuronal cells, retinal ganglion cells, and inflammatory cell infiltration.
- 3. The use of the miRNA-200s protectant according to claim 1, wherein the neurological condition is one of cns demyelination, neuronal damage, and optic neuritis.
- 4. The application of the miRNA-200s protective agent in the preparation of medicines for nervous system diseases according to claim 1, wherein the miRNA-200s protective agent is administered at a dose of 1nmol/20g of body weight, and is administered to Balb/c mice and other animals with central nervous system injury by intracranial stereotaxic injection or intravenous injection.
- 5. The use of the miRNA-200s protective agent of claim 1 in the preparation of a medicament for the treatment of a nervous system disorder, wherein the nervous system disorder comprises a variety of central nervous system disorders caused by Angiostrongylus cantonensis infection.
- 6. The medicine for treating the nervous system diseases is characterized by comprising a miRNA marker related to the protection of nervous system injuries, wherein the miRNA marker comprises miRNA-200a-3p, miRNA-200b-5p, miRNA-200c-3p, miRNA-429-3p and miRNA-141-5p.
- 7. A medicament for treating nervous system diseases, which is characterized by comprising a miRNA marker related to nervous system injury protection, wherein the gene sequence of the miRNA marker is (5 'to 3') mmu-miR-200a-3P-F TAACACTGTCTGGTAACGATGT; mmu-miR-200 b-5P-FCATCTTTACTGGGCAGCATTGGA; mmu-miR-200 c-3P-FTAATACTGCCGGTAATGATGGA; mmu-miR-429-3P-FTAATACTGTCTGGTAATGCGCT; mmu-miR-141-5P-FCATCTTCCAGTGCAGTTGGGA.
- 8. The method for constructing the verification model of the nervous system disease drug according to claim 6 or 7, wherein the model construction method comprises: the injection is used for injecting the nervous system disease medicament into a mouse after the model building of the nervous system disease, and is safe and effective to model animals without obvious side effect and complication.
- 9. The method for constructing a disease-based drug verification model according to claim 8, comprising the following steps:1) Selecting a mouse for modeling nervous system diseases;2) After molding, injecting the nervous system disease drug into the mice;3) Then, the damage condition and the brain damage degree of the oligodendrocyte, the neuron cell and the retinal ganglion cell of the mouse are detected.
- 10. The method for constructing verification model of nervous system disease drug according to claim 8, wherein the detection method is immunofluorescence, magnetic resonance imaging technique and/or LFB staining.
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