CN106039290A - Exploration and application of erythropoietin in severe cervical spondylosis cervical cord injury - Google Patents
Exploration and application of erythropoietin in severe cervical spondylosis cervical cord injury Download PDFInfo
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- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 title claims abstract description 148
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- A61K38/1816—Erythropoietin [EPO]
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Abstract
The invention discloses a research and application of erythropoietin in severe cervical spondylosis cervical cord injury, which comprises erythropoietin cell test research, animal experiments and clinical application research, wherein the research materials, methods and steps of the erythropoietin are as follows: s1, researching the intervention effect of EPO on bone marrow mesenchymal stem cells cultured in vitro, S2, researching that EPO and the bone marrow mesenchymal stem cells treat acute spinal cord injury of rats, and S3, researching that EPO treats cervical marrow injury in clinic. According to the invention, through researches on three aspects of cells, animals and clinics, the treatment effect of erythropoietin on spinal cord injury is obvious, and the erythropoietin can be used for single or synergistic treatment with bone marrow mesenchymal stem cells, methylprednisolone and the like, so that severe spinal cord injury type cervical spondylosis can be effectively treated.
Description
Technical field
The present invention relates to pharmaceutical technology field, particularly relate to the medicinal usage of erythropoietin, be mainly used in instructing
The Drug therapy of clinical Cervical cord injuries and clinic study, be specifically related to a kind of erythropoietin at serious symptom cervical spondylosis neck
Probing into and applying in marrow damage.
Background technology
Erythropoietin (erythropoietin, EPO), is also called erythrocyte growth factor, for molecular weight 34kD
Containing sialic acidoglycoprotein.EPO is that one acts on myeloid element, promotes CFU-E hypertrophy, differentiation
The most ripe endocrine hormone, thought that EPO was a kind of cytokine regulating hemopoietic and differentiation in the past, recently studied
Confirm that EPO also has the powerful neuroprotectives such as anti-inflammatory, antioxidation, anti-excitotoxin and anti-apoptotic, be
A kind of multifunctional and nutritional factor and neuroprotective factor, have regulation development of central nervous system, neurotrophy and neuroprotective
Effect.
Using EPO to carry out the treatment of animal spinal cord damage, EPO can directly act on neural stem cell, induction god for a long time
Through the expression of trophic factors, promote impaired place neuranagenesis.Studies have found that, at experimental autoimmune encephalomyelitis model
In, EPO can strengthen the propagation of oligodendrocyte and the regeneration of myelin, thus function of nervous system extensive after promoting spinal cord injury
Multiple.Additionally, EPO can also promote that nerve cell axons regenerates, regulate body vasospasm, stimulate new vessels to be formed, thus
For the microenvironment that the reparation offer of spinal cord injury is good, the recovery to spinal function is highly profitable.But at present, EPO is to neck marrow
After damage, the research of therapy mechanism is in animal experiment stage, and the individual difference of application is relatively big clinically, EPO application clinically
There is also many problem demanding prompt solutions.
Along with the increase of life stress, the increasing of vehicle accident, the sickness rate of serious symptom cervical spondylosis and cervical spinal injury gradually increases
Adding, Cervical cord injuries also gets more and more, no matter Acute Cervical Spinal Cord Injury or chronic cervical cord injury, suffers from poor prognosis, thus
People are in the urgent need to furtheing investigate EPO, and are applied in the middle of clinic by EPO.
Summary of the invention
The technical problem existed based on background technology, the present invention proposes a kind of erythropoietin in serious symptom cervical spondylosis
Probing into and applying in Cervical cord injuries.
The present invention provides following technical scheme:
The probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, grows including promoting erythrocyte
Element test cell line research, zoopery and clinical application research, the research material of this erythropoietin, method are with step such as
Lower described:
S1, research erythropoietin (EPO) intervention effect to the mesenchymal stem cells MSCs of In vitro culture:
1) choice experiment rat, separates, cultivates rat bone marrow mesenchymal stem cells,
2) the 3rd generation mesenchymal stem cells MSCs (Bone marrow mesenchymal stem cell, BMSCs), nothing are taken
Under serum condition, according to use EPO variable concentrations (0.50,1.00,2.00,4.00,10.00U/mL) packet, and between bone marrow
Mesenchymal stem cells co-cultivation is experimental group, and the mesenchymal stem cells MSCs being not added with EPO is blank, row MTT inspection after 96h
Survey, observe the proliferative conditions of mesenchymal stem cells MSCs, calculate Proliferating antigen Ki67, and compare,
3) taking the 3rd generation mesenchymal stem cells MSCs, erythropoietin 10U/mL is common with mesenchymal stem cells MSCs
Cultivate, after 96h, use flow cytometry analysis cell generation cycle；
S2, research erythropoietin (EPO) and bone mesenchymal stem cells treatment rat acute spinal cord injury:
S2-1, research erythropoietin (EPO) mobilization bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 30 SD rats being randomly divided into sham operated rats, normal saline group and EPO treatment group, each group is all noted through tail vein
Penetrate the BMSCs of Hoechst3342 labelling,
2) transplant after 1,3,7,14,21,28d use BBB method carry out rat hindlimb motor function scores observe rat
Functional rehabilitation situation, application Immunofluorescence test is respectively organized BMSCs and is mobilized the number at spinal cord injury, Westernblot
Detection damage local BMSCs expresses Brain Derived Neurotrophic Factor (BDNF) and the level of nerve growth factor (NGF)；
S2-2, research erythropoietin (EPO) associating bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 75 SD rats are randomly divided into spinal cord injury group, EPO treatment group, BMSCs treatment group, EPO+BMSCs treatment
Group and sham operated rats, totally 5 groups, often group 15, use improvement Allen method to make rat acute spinal cord injury (acute spinal
Cord injury, ASCI) model,
2) EPO treatment is 24h lumbar injection recombinant human erythropoietin (rhEPO) 5000U/ before spinal cord injury
Kg, BMSCs treatment be by the BMSCs of purification when spinal cord injury through tail vein injection, within postoperative 1st, 3,7,14,21,28 days, adopt
Carrying out rat hindlimb motor function scores by BBB method, observe rat functional rehabilitation situation, HE dyeing in postoperative 1st, 28 days is seen
Examine spinal cord morphological change,
3), Western blot detects the 14th day damage local cerebral derived neurotrophic factor (brain derived
Neurotrophic factor, BDNF) expression；
Cervical cord injuries in S3, research erythropoietin (EPO) treatment clinic:
S3-1, the clinical practice of research erythropoietin (EPO) associating prednisolone treatment spinal cord injury:
1) Patients of Spinal 55 case that my section of retrospective analysis previously accepts for medical treatment, is randomly divided into EPO and combines prednisolone group
With prednisolone group.Within before treatment, after treatment 1 week and 1 year, press ASIA (ASIA) standard row Neuroscore, system
Meter function of nervous system improvement rate, parallel activities of daily living (activity of daily living, ADL) scoring is compared.
S3-2, research erythropoietin (EPO) are in the application of Cervical cord injuries peri-operation period:
1) retrospective analysis is previously in severe cervical spondylotic myelopathy Cervical cord injuries case 43 example of my section's row operative treatment, with
Machine is divided into two groups, and wherein 22 example A group peri-operation periods use EPO, and 21 example B groups do not use EPO, record preoperative, art one week after, art
Within latter 1 year, by the neurological functional recovery rate of JOA (JOA) score calculation patient, add up complication.Use ODOM standard
The change of assessment function of nervous system at a specified future date.
The invention provides the probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, pass through
Cell, animal, the research of clinical three aspects, recognize that erythropoietin can be to the therapeutic effect of spinal cord injury deeply
Significantly, use erythropoietin, can directly regulate affected area circulation volume, promote the generation of new vessels, promote bone
Bone marrow-drived mesenchymal stem secretion VEGF, increases the formation of affected area new vessels, and effectively mobilizes bone marrow
Mescenchymal stem cell migrates to site spinal cord injury, promotes it to express Brain Derived Neurotrophic Factor and nerve growth factor adds
The recovery of the fast function of nervous system that moves, has the effect of neurotrophy and neuroprotective, it is possible to by promoting brain-derived neurotrophy
The expression of the factor, can play long-term neurotrophic effect, thus effectively treat severe cervical spondylotic myelopathy, simultaneously can be independent
Or with the Synergistic treatment Cervical cord injuries such as mesenchymal stem cells MSCs, prednisolone, at the peri-operation period of serious symptom cervical spondylosis Cervical cord injuries
Use safely and effectively so that the neurological functional recovery of serious symptom cervical spondylosis Cervical cord injuries patient is very fast, improve serious symptom myeloid form cervical vertebra
The recovery rate of function of nervous system after sick Cervical cord injuries operation in patients, and then greatly improve erythropoietin for serious symptom cervical spondylosis
Feasibility, safety and effectiveness in the middle of Cervical cord injuries.
Detailed description of the invention
Below, by specific embodiment, technical scheme is described in detail.
Embodiment 1
The probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, research promoting erythrocyte growth
Element (EPO) intervention effect to the mesenchymal stem cells MSCs of In vitro culture:
1) choice experiment rat, separates, cultivates rat bone marrow mesenchymal stem cells,
2) the 3rd generation mesenchymal stem cells MSCs (BMSCs) is taken, under serum-free condition, according to the variable concentrations using EPO
(0.50,1.00,2.00,4.00,10.00U/mL) packet, be experimental group with mesenchymal stem cells MSCs co-cultivation, be not added with
The mesenchymal stem cells MSCs of EPO is blank,
3) row MTT detection after 96h, observes the proliferative conditions of mesenchymal stem cells MSCs, calculates Proliferating antigen Ki67, and
Compare,
4) taking the 3rd generation mesenchymal stem cells MSCs, erythropoietin 10U/mL is common with mesenchymal stem cells MSCs
Cultivate, after 96h, use flow cytometry analysis cell generation cycle.
In the present embodiment 1 test cell line, after EPO processes, the propagation of BMSCs cell increases notable, and EPO concentration is more
Greatly, action time is the longest, and its propagation usefulness is more obvious, i.e. EPO is that dose dependent promotes Proliferation of Bone Mesenchymal Stem Cells, with
During the concentration of 10U/mL, EPO promotes that BMSCs proliferation function is the most obvious.Matched group BMSCs stage of latency G0/G1 ratio is higher,
(85.1 scholar 0.61) %, synthesis the S phase and proliferation and differentiation G2/M phase ratio relatively low be respectively (10.64 ± 0.37) %,
(4.26 scholar 0.69) %；After co-culturing 96h with the EPO of I0U/mL, G0/Gl phase ratio is reduced to (69.0 scholar 0.89) %, and the S phase
Increase with G2/M phase cell proportion and be respectively (22.1 scholar 0.47) %, (8.9 scholar 0.93) %.
Embodiment 2
The probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, research promoting erythrocyte growth
Element (EPO) and bone mesenchymal stem cells treatment rat acute spinal cord injury:
A1, research erythropoietin (EPO) mobilization bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 30 SD rats being randomly divided into sham operated rats, normal saline group and EPO treatment group, each group is all noted through tail vein
Penetrate the BMSCs of Hoechst3342 labelling,
2) transplant after 1,3,7,14,21,28d use BBB method carry out rat hindlimb motor function scores observe rat
Functional rehabilitation situation,
3) application Immunofluorescence test is respectively organized BMSCs and is mobilized the number at spinal cord injury, and Westernblot detects
Damage local BMSCs expresses Brain Derived Neurotrophic Factor (BDNF) and the level of nerve growth factor (NGF)；
A2, research erythropoietin (EPO) associating bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 75 SD rats are randomly divided into spinal cord injury group, EPO treatment group, BMSCs treatment group, EPO+BMSCs treatment
Group and sham operated rats, totally 5 groups, often group 15,
2) improvement Allen method is used to make rat acute spinal cord injury (acute spinal cord injury, ASCI)
Model, EPO treatment is 24h lumbar injection recombinant human erythropoietin (rhEPO) 5000U/kg before spinal cord injury,
BMSCs treatment be by the BMSCs of purification when spinal cord injury through tail vein injection,
3) Post operation uses BBB method to carry out rat hindlimb motor function scores for the 1st, 3,7,14,21,28 days, observes rat
Neurological functional recovery situation, postoperative 1st, 28 days HE dyeing observation spinal cord morphological change,
4), Western blot detects the 14th day damage local cerebral derived neurotrophic factor (brain derived
Neurotrophic factor, BDNF) expression.
In the present embodiment 2 animal experiment A1 step, after spinal cord injury 24 hours, normal saline group and EPO treatment group big
The BBB scoring no significant difference of the double hind limb motor function of Mus；Postoperative 3 days, the function of nervous system of two groups of rats all had in various degree
Recover, but the motor function scores of EPO treatment group is apparently higher than normal saline group；Within 1st day, rise, can be observed under fluorescence microscope
At the myeloid tissue of each group and adjacent groups is woven with the BMSCs of Hoechst3342 labelling, from the 3rd day, EPO treatment group spinal cord
The quantity of damage local BMSCs is substantially many than normal saline group, compares with normal saline group, and EPO treatment group is opened for the 3rd day after surgery
The expression showed increased of beginning BDNF and NGF.
In the present embodiment 2 animal experiment A2 step, show through histological observation, postoperative 1st day sham operated rats spinal cord group
Knitting structure normal, neurocyte form is intact, has no that swelling changes, and nucleus circle, it is seen that kernel, in remaining Ge Zu myeloid tissue
Visible point, lamellar are hemorrhage, and partial nerve cellular swelling, cavity are formed, and nucleus offsets, and kernel is the most clear；Within postoperative 28th day, do evil through another person
Shu Zu myeloid tissue structure is normal, and neurocyte form is intact；Substantially cavity, spinal cord injury group myeloid tissue local is formed, in a large number
Scar tissue, neurocyte is rare, and EPO group and BMSCs group injured spinal tissue local cavity, neurocyte is more, EPO+
Formed without substantially cavity and scar tissue in BMSCs group myeloid tissue, have a large amount of neurocyte, cell body and projection clearly may be used
See；Within postoperative 3 days, rising, EPO group, BMSCs group, the recovery of function of nervous system of EPO+BMSCs group are substantially better than spinal cord injury group, and
Function of nervous system's improvement of EPO+BMSCs group is significantly higher than EPO group and BMSCs group, Western-Blot result display sham operated rats
BDNF expression minimum, the BDNF expression of spinal cord injury group slightly raises, and the BDNF of EPO group and BMSCs group expresses
Level is the most significantly raised compared with spinal cord injury group, and the expression of the BDNF of EPO+BMSCs group is apparently higher than single treatment group.
Embodiment 3
The probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, research promoting erythrocyte generates
Cervical cord injuries in element (EPO) treatment clinic:
B1, the clinical practice of research erythropoietin (EPO) associating prednisolone treatment spinal cord injury:
1) Patients of Spinal 55 case that my section of retrospective analysis previously accepts for medical treatment, is randomly divided into EPO and combines prednisolone group
With prednisolone group,
2) before treatment, within after treatment 1 week and 1 year, ASIA (ASIA) standard row Neuroscore, system are pressed
Meter function of nervous system improvement rate, parallel activities of daily living (activity of daily living, ADL) scoring is compared.
B2, research erythropoietin (EPO) are in the application of Cervical cord injuries peri-operation period:
1) retrospective analysis is previously in severe cervical spondylotic myelopathy Cervical cord injuries case 43 example of my section's row operative treatment,
2) being randomly divided into two groups, wherein 22 example A group peri-operation periods use EPO, and 21 example B groups do not use EPO, record art
Before, art one week after, the postoperative 1 year neurological functional recovery rate by JOA (JOA) score calculation patient, statistics is concurrent
Disease.
3) use ODOM criterion evaluation function of nervous system in long term change.
In the present embodiment 3 clinical application research B1 step, Long-term does not finds hormone dependency femur head necrosis, pathology
Property the complication such as fat, bone-graft fusion is good, interior fixing-stable；After treatment 1 week and 1 year, MPSS group and EPO+MPSS group patient
Neuroscore is more preoperative to be increased significantly, and EPO+MPSS group is higher, and EPO+MPSS group compares to use merely MPSS group,
Function of nervous system's improvement rate is higher, compared with before treatment；Within after treatment 1 week and 1 year two groups of patient ADL, mark and all significantly improve, between group
Relatively, after treatment 1 week and 1 year, the scoring of EPO+MPSS group ADL was apparently higher than alone MPSS group.
In the present embodiment 3 clinical application research B2 step, the severe cervical spondylotic myelopathy neck marrow at section's row operative treatment damages
Hinder patient, all obtain more than 1 year and follow up a case by regular visits to, in following up a case by regular visits to, do not find hypertension, thrombus disease, the cardiovascular and cerebrovascular vessel complication such as surprisingly；Image
Learn prompting bone-graft fusion good, interior fixing non-loosening, rupture, the situation such as come off occurs；The recovery of the function of nervous system of application EPO group
Significantly better than unused EPO group；ODOM classification and the improvement rate of application EPO group are substantially better than unused EPO group.
Above-described embodiment 1-3 needs to carry out BMSCs in rat peripheral blood, bone marrow and measures；Rat hindlimb motor function scores；
The preparation of Model of Rat Spinal Cord Injury；Spinal Cord Injury in Rats site tissue is observed, related cell adhesion molecule, neurotrophic factor
Immunohistochemical analysis；The scoring of clinical patients ASIA, activities of daily living scoring, JOA scoring；Check the function of nervous system of clinical patients
Improvement, neurological functional recovery rate.Following research conclusion is drawn: between (1), erythropoietin are to bone marrow by embodiment 1-3
The growth of mesenchymal stem cells and migration have obvious facilitation；(2) medulla mesenchyma can effectively be mobilized by erythropoietin
Stem cell migrates to site spinal cord injury, it is also possible to promote it to express Brain Derived Neurotrophic Factor and nerve growth factor adds
The recovery of the fast function of nervous system that moves；(3) erythropoietin the most directly regulates affected area circulation volume, promotes new hemopoietic
The generation of pipe, moreover it is possible to promote mesenchymal stem cells MSCs to secrete VEGF, increase affected area new vessels
Formed, thus treat Cervical cord injuries；(4) Cervical cord injuries that wound is caused, erythropoietin have neurotrophy and
The effect of neuroprotective, the Neuron Apoptosis that suppression Cervical cord injuries causes is its short run effect, and it is by promoting brain source property simultaneously
The expression of neurotrophic factor, can play long-term neurotrophic effect；(5) erythropoietin is at serious symptom cervical spondylosis neck marrow
The peri-operation period of damage uses safely and effectively, can significantly improve function of nervous system after severe cervical spondylotic myelopathy Cervical cord injuries operation in patients
Recovery rate；(6) protective effect that erythropoietin shows in serious symptom cervical spondylosis Cervical cord injuries is treated, the most logical
Cross and alleviate local inflammation reaction, the necrosis of inhibitory neuron and apoptosis, the expression of promotion local nerve somatomedin, mobilization body
Stem cell assembles to damage location and finally realizes the regeneration of neuron and glial cell and realizes with repairing, and promoting erythrocyte is given birth to
Cheng Su, as a kind of neuroprotective factor and the multifunctional and nutritional factor, is possible not only to regulate development of central nervous system, plays god
Through nutrition and the effect of neuroprotective；The expression of nerve growth factor and neurotrophic factor-3 can be increased；Can also be substantially
Ground reduces neuronal apoptosis, thus suppresses secondary spinal cord injury.
By cell, animal, the research of clinical three aspects, inquire into the neck that a variety of causes is caused by erythropoietin
Marrow damage gives probability and the mechanism for the treatment of, and reasoning is tight；Experimental design takes into account science principle and the economic principle of experiment, tool
There is the strongest operability.
The present invention, by test cell line, zoopery and the research of clinical three aspects, observes erythropoietin pair
The propagation of mesenchymal stem cells MSCs, break up, the impact of the process such as migration；Observe through erythropoietin and medulla mesenchyma
The pathology of rats with spinal cord injury, behavioristics after stem cell process change；Observe erythropoietin associating prednisolone pair
Patients of acute spinal cord injury function of nervous system improves situation and daily life active ability recovery situation；And by erythropoietin
Among the treatment of the peri-operation period being used in serious symptom cervical spondylosis Cervical cord injuries patient, erythropoietin can be conducive to serious symptom ridge
The feasibility of marrow myelopathy treatment, effectiveness and reliability, for the treatment of clinical severe cervical spondylotic myelopathy provide new approaches,
New method.
The invention provides the probing into and applying in serious symptom cervical spondylosis Cervical cord injuries of a kind of erythropoietin, pass through
Cell, animal, the research of clinical three aspects, recognize that erythropoietin can be to the therapeutic effect of spinal cord injury deeply
Significantly, use erythropoietin, can directly regulate affected area circulation volume, promote the generation of new vessels, promote bone
Bone marrow-drived mesenchymal stem secretion VEGF, increases the formation of affected area new vessels, and effectively mobilizes bone marrow
Mescenchymal stem cell migrates to site spinal cord injury, promotes it to express Brain Derived Neurotrophic Factor and nerve growth factor adds
The recovery of the fast function of nervous system that moves, has the effect of neurotrophy and neuroprotective, it is possible to by promoting brain-derived neurotrophy
The expression of the factor, can play long-term neurotrophic effect, thus effectively treat severe cervical spondylotic myelopathy, simultaneously can be independent
Or with the Synergistic treatment Cervical cord injuries such as mesenchymal stem cells MSCs, prednisolone, at the peri-operation period of serious symptom cervical spondylosis Cervical cord injuries
Use safely and effectively so that the neurological functional recovery of serious symptom cervical spondylosis Cervical cord injuries patient is very fast, improve serious symptom myeloid form cervical vertebra
The recovery rate of function of nervous system after sick Cervical cord injuries operation in patients, and then greatly improve erythropoietin for serious symptom cervical spondylosis
Feasibility, safety and effectiveness in the middle of Cervical cord injuries.
The above, the only present invention preferably detailed description of the invention, but protection scope of the present invention is not limited thereto,
Any those familiar with the art in the technical scope that the invention discloses, according to technical scheme and
Inventive concept equivalent or change in addition, all should contain within protection scope of the present invention.
Claims (1)
1. erythropoietin probing into and applying in serious symptom cervical spondylosis Cervical cord injuries, it is characterised in that: include promoting
The research of erythropoietin test cell line, zoopery and clinical application research, the research material of this erythropoietin, side
Method is as described below with step:
S1, research erythropoietin (EPO) intervention effect to the mesenchymal stem cells MSCs of In vitro culture:
1) choice experiment rat, separates, cultivates rat bone marrow mesenchymal stem cells,
2) the 3rd generation mesenchymal stem cells MSCs (Bone marrow mesenchymal stem cell, BMSCs), serum-free are taken
Under the conditions of, according to use EPO variable concentrations (0.50,1.00,2.00,4.00,10.00U/mL) packet, with medulla mesenchyma
Stem cell co-cultivation is experimental group, and the mesenchymal stem cells MSCs being not added with EPO is blank, row MTT detection after 96h,
Observe the proliferative conditions of mesenchymal stem cells MSCs, calculate Proliferating antigen Ki67, and compare,
3) the 3rd generation mesenchymal stem cells MSCs, erythropoietin 10U/mL and mesenchymal stem cells MSCs co-cultivation are taken,
Flow cytometry analysis cell generation cycle is used after 96h；
S2, research erythropoietin (EPO) and bone mesenchymal stem cells treatment rat acute spinal cord injury:
S2-1, research erythropoietin (EPO) mobilization bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 30 SD rats are randomly divided into sham operated rats, normal saline group and EPO treatment group, respectively organize all through tail vein injection
The BMSCs of Hoechst3342 labelling,
2) transplant after 1,3,7,14,21,28d use BBB method carry out rat hindlimb motor function scores observe rat function
Recovery situation, application Immunofluorescence test is respectively organized BMSCs and is mobilized the number at spinal cord injury, Westernblot detection
Damage local BMSCs expresses Brain Derived Neurotrophic Factor (BDNF) and the level of nerve growth factor (NGF)；
S2-2, research erythropoietin (EPO) associating bone mesenchymal stem cells treatment rat acute spinal cord injury:
1) 75 SD rats are randomly divided into spinal cord injury group, EPO treatment group, BMSCs treatment group, EPO+BMSCs treatment group and
Sham operated rats, totally 5 groups, often group 15, use improvement Allen method to make rat acute spinal cord injury (acute spinal cord
Injury, ASCI) model,
2) EPO treatment is 24h lumbar injection recombinant human erythropoietin (rhEPO) 5000U/kg before spinal cord injury,
BMSCs treatment be by the BMSCs of purification when spinal cord injury through tail vein injection, postoperative 1st, 3,7,14,21,28 days use
BBB method carries out rat hindlimb motor function scores, observes rat functional rehabilitation situation, and HE dyeing in postoperative 1st, 28 days is observed
Spinal cord morphological change,
3), Western blot detects the 14th day damage local cerebral derived neurotrophic factor (brainderived
Neurotrophic factor, BDNF) expression；
Cervical cord injuries in S3, research erythropoietin (EPO) treatment clinic:
S3-1, the clinical practice of research erythropoietin (EPO) associating prednisolone treatment spinal cord injury:
1) Patients of Spinal 55 case that my section of retrospective analysis previously accepts for medical treatment, is randomly divided into EPO associating prednisolone group and first
Strong dragon group.Within before treatment, after treatment 1 week and 1 year, by ASIA (ASIA) standard row Neuroscore, statistics is refreshing
Through function improvement rate, parallel activities of daily living (activity of daily living, ADL) scoring is compared.
S3-2, research erythropoietin (EPO) are in the application of Cervical cord injuries peri-operation period:
1) retrospective analysis is previously in severe cervical spondylotic myelopathy Cervical cord injuries case 43 example of my section's row operative treatment, divides at random
Being two groups, wherein 22 example A group peri-operation periods use EPO, and 21 example B groups do not use EPO, record preoperative, art one week after, postoperative one
Year, by the neurological functional recovery rate of JOA (JOA) score calculation patient, adds up complication.Use ODOM criterion evaluation
Function of nervous system at a specified future date change.
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