CN103622941A - Application of sulindac in preparation of medicine for treating autism - Google Patents
Application of sulindac in preparation of medicine for treating autism Download PDFInfo
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- CN103622941A CN103622941A CN201310693076.2A CN201310693076A CN103622941A CN 103622941 A CN103622941 A CN 103622941A CN 201310693076 A CN201310693076 A CN 201310693076A CN 103622941 A CN103622941 A CN 103622941A
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Abstract
The invention discloses application of sulindac in preparation of a medicine for treating autism. The application of sulindac in preparation of the medicine for treating autism is characterized in that a VPA (Valproic Acid) autism animal model shows that sulindac is able to reduce abnormal behavior of an autistic, such as repeated mechanical behavior deficiency and human communication disorders; the primary culture neuron and VPA autism animal model verify the occurrence mechanism of autism as well as the functional mechanism of sulindac in treating autistic, and also prove that sulindac has oxidation resistance, and the oxidation resistance is related to down-regulating of the activity of a canonical Wnt signal channel. Therefore, sulindac is able to reduce the repeated mechanical behavior, abnormal behavior and human communication disorders of the autistic and can be used for preparing the medicine for treating autism.
Description
Technical field
The invention belongs to medical technical field, be specifically related to the application of a kind of sulindac aspect the autistic medicine of preparation treatment.
Background technology
Autism (Autism), claims again infantile autism or autistic disorder etc., is the representative disease of pervasive developmental disorders.Autism main manifestations is three major types core symptom: development of speech delay, Social behaviors obstacle, the stiff limitation of behavior.Development of speech postpones to refer to that speech zoon or part postpone, and without the trial of wanting for example, to replace by other modes (gesture or echopraxia); There is the ability person that necessarily speaks, proposing topic and maintaining aspect the ability of talk have obvious damage; Use language mechanical or that repeat or special, only have and oneself listen to obtain the language understood.Social behaviors obstacle refers to that the application of nonverbal communication behavior exists significantly infringement; Can not associate with age cohorts; Can not spontaneously share joy, interest, achievement etc. with others; In social and emotion can not with the mutual effect of Crinis Carbonisatus looks.The stiff limitation of behavior refers to that one or more are fixing, that repeat, the interest of limitation, and its degree and content all belong to normally, and malleable not; Follow doggedly certain special, nonsensical routine or ceremony; The behavior of posing of mechanical repetition; The long-term part of only paying close attention to things continuing.
Along with the increase of autism prevalence, autism is more and more subject to the common concern of countries in the world, and the sickness rate of global childhood autism is approximately 1/100, far away higher than cancer, diabetes etc.Autism infringement field in infant growth and development process is extensive, and most of infant can not be socially reintegrated, and badly influences physical and mental health and the quality of life of infant; Autism belongs to chronic disease, and approximately 2/3 infant cannot be lived on one's own life after growing up, and needs treatment throughout one's life and maintenance ，Gei family and society to bring heavy burden, becomes the great public health problem that affects children's health and social stability.Therefore, autism has been not only individual disease, and its diagnosis and treatment and rehabilitation have become the great public health problem of urgently studying and solving.
Summary of the invention
The object of this invention is to provide the application of a kind of sulindac aspect the autistic medicine of preparation treatment.
In order to realize above object, the technical solution adopted in the present invention is: the application of sulindac aspect the autistic medicine of preparation treatment.
Application aspect the medicine that sulindac postpones at preparation treatment development of speech.
The application of sulindac aspect the medicine of preparation treatment Social behaviors obstacle.
Sulindac is in the application of preparing aspect the medicine of the stiff limitation for the treatment of behavior.
Along with people more and more study autism molecular pathology; autistic pathogenesis is more and more paid close attention to effect (the Wang Z of classical Wnt signal path in autism morbidity; Xu L; Zhu X; et al.Demethylation of specific Wnt/beta-catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure.Anat Rec (Hoboken); 2010,293 (11): 1947-53; Zhang Y, Sun Y, Wang F, et al.Downregulating the Canonical Wnt/beta-catenin Signaling Pathway Attenuates the Susceptibility to Autism-like Phenotypes by Decreasing Oxidative Stress.Neurochem Res, 2012.).Classical Wnt signal path contributes to cell proliferation in embryo development procedure, cell differentiation, apoptosis and cell migration.Because classical Wnt signal path acts on widely, its functional disorder also plays illeffects widely to neurodevelopment, can cause the autistic generation of neurodevelopment obstacle disease.Studies show that classical Wnt signal path participates in autistic pathogenesis, it is abnormal that the induction of classical Wnt signal path functional disorder is similar to the morphology and function of autistic patients.β-catenin transgenic mouse forms huge brain, cause brain cortex capacity to increase (Chenn A, Walsh CA.Regulation of cerebral cortical size by control of cell cycle exit in neural precursors.Science, 2002, 297 (5580): 365-9.), and β-catenin inactivation causes brain and cranium developmental disorder (Brault V, Moore R, Kutsch S, et al.Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.Development, 2001, 128 (8): 1253-64.).Autism model mouse β-catenin up-regulated, its downstream target gene is also lowered, simultaneously along with its expression of change in time and space is abnormal.The sudden change of a gene in signal path, can cause neurodevelopment and behavioristics's performance extremely as increased the activation of downstream signal path signal molecule after Wnt1 sudden change.Result of study shows, the sudden change of Wnt1 antisense causes Wnt signal path to activate and contributes to autistic susceptibility (Martin PM, Yang X, Robin N, et al.A rare WNT1missense variant overrepresented in ASD leads to increased Wnt signal pathway activation.Transl Psychiatry, 2013,3:e301.).
Sulindac, another name Sulindac, is antipyretic-antalgic and non_steroidal anti_inflammatory drug; For osteoarthritis, rheumatoid arthritis, scapulohumeral periarthritis, neck shoulder wrist syndrome, tenosynovitis etc.; The pain causing for a variety of causes, as dysmenorrhea, toothache, wound and postoperative pain; Also can be used for light, moderate cancerous pain.
Sulindac is the nonsteroidal anti-inflammatory drug of FDA approval, has antitumor character; It has many functions as a kind of nonsteroidal anti-inflammatory drug; a kind of specific inhibitor that is used as classical Wnt signal path; it is β-catenin pharmacology inhibitor; can prevent that β-catenin from shifting (Huang Y by endochylema to karyon; Chang X; Lee J; et al.Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein2in human esophageal squamous cell carcinoma.Int J Cancer; 2011,128 (10): 2261-73; Lemjabbar-Alaoui H, Dasari V, Sidhu SS, et al.Wnt and Hedgehog are critical mediators of cigarette smoke-induced lung cancer.PLoS One, 2006,1:e93.).Antiinflammatory reagent and polyphenoils have neuroprotective character, are conducive to treat neurodevelopment obstacle disease, as autism.
The application of sulindac of the present invention aspect the autistic medicine of preparation treatment, adopts VPA autism animal model, has proved that sulindac can improve the behavioristics of autism sample abnormal, as has repeated stiff sample behavioral deficiency, Social behaviors obstacle; By former culture neuron and VPA autism animal model, verified the mechanism that autism occurs, and sulindac improves the mechanism of action of autism sample, proof sulindac has antioxidant properties, and its antioxidant properties is relevant with downward classical Wnt signal path activity; What sulindac can reduce autism sample repeats stiff sample dystropy and Social behaviors obstacle, can be used for the autistic medicine of preparation treatment.
The application of sulindac of the present invention aspect the autistic medicine of preparation treatment, sulindac can reduce the GSK-3 β phosphorylation of inactivation, increases β-catenin phosphorylation of inhibition, thus it is active to lower classical Wnt signal path; And reduce the generation of 4-HNE and ROS, reduce oxidative stress; Spacious experimental result shows, VPA autism animal model repeat stiff sample behavior VPA and sulindac while processed group be improved significantly; The demonstration of Social Interaction behavior outcome, it is abnormal that sulindac can improve the Social behaviors of VPA autism animal model.Experiment is also observed, and after former culture neuron activates classical Wnt signal path with VPA, sulindac is processed the generation that has reduced 4-HNE and ROS when reducing classical Wnt signal path; And antioxidant NAC processing has reduced 4-HNE and ROS produces, but the expression of do not change GSK-3 β and β-catenin.These presentation of results: sulindac has antioxidant properties, and its antioxidant properties is relevant with downward classical Wnt signal path activity; What sulindac can reduce autism sample repeats stiff sample dystropy and Social behaviors obstacle, can be used for the autistic medicine of preparation treatment.
Accompanying drawing explanation
What Fig. 1 was variable concentrations VPA on former culture neuron GSK-3 β and β-catenin affects testing result schematic diagram;
Fig. 2 former culture neuron 4-HNE expression that to be NAC process VPA affect testing result schematic diagram;
Fig. 3 former culture neuron ROS expression that to be NAC process VPA affect testing result schematic diagram;
Fig. 4 former culture neuron GSK-3 β mRNA that to be NAC process VPA and β-catenin mrna expression affect testing result schematic diagram;
Fig. 5 former culture neuron GSK-3 β mRNA that to be sulindac process VPA and β-catenin mrna expression affect testing result schematic diagram;
Fig. 6 former culture neuron P-GSK-3 β that to be sulindac process VPA and P-β-catenin expression affect testing result schematic diagram;
Fig. 7 former culture neuron 4-HNE expression that to be sulindac process VPA affect testing result schematic diagram;
To be sulindac repeat slow-witted sample behavior to VPA autism animal model to Fig. 8 affects testing result schematic diagram;
What Fig. 9 was sulindac on VPA autism animal model oneself reason hair and upright behavior affects testing result schematic diagram;
What Figure 10 was sulindac on VPA autism animal model Social behaviors affects testing result schematic diagram.
The specific embodiment
Below in conjunction with the specific embodiment, the present invention is further illustrated.
In the experimental example of the specific embodiment, sulindac used is the powder purchased from Sigma company, during use, sulindac is used to DMSO(dimethyl sulfoxide) make after solution and become to need concentration with normal saline dilution; In zoopery, giving the dosage of rat is 5mg/kg.
Sulindac is in the application of preparing aspect the medicine of the stiff limitation for the treatment of behavior.
Laboratory animal and VPA(sodium valproate) autism Animal Model.
Laboratory animal: healthy adult Wistar male (300～350g) and female (200～250g) rat, purchased from laboratory animal portion of the Chinese Academy of Sciences (Shanghai), raising in Fudan University's Human Anatomy, Histology and Embryology is special-purpose Animal House, gives sufficient feedstuff and drinking-water.All laboratory animals are fed and the equal adhere rigidly to of experimental arrangement Fudan University laboratory animal protective provisions.
VPA autism Establishment of Rat Model basic process is as follows: grow up female and each several of male Wistar rats, under periodicity illumination (7:00AM～7:00PM), 25 ℃ of constant temperature and constant humidity 55% condition, raise a few days, and make it to conform.Then, by female: hero spends the night for 2:1 mates.Morning, the female Mus that is checked through cloudy bolt is designated as E1, then divides cage to raise separately.Method (Schneider T with reference to uses such as Schneider, Turczak J, Przewlocki R.Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid:issues for a therapeutic approach in autism.Neuropsychopharmacology, 2006, 31 (1): 36-46.), female Mus of becoming pregnant is divided into two groups at random, one group gave female Mus ip(lumbar injection in the time of E12.5 days) the VPA(sodium valproate of 600mg/kg), 0.85% normal saline (Normal saline for VPA powder, NS) be made into the solution of 250mg/ml, for model group, the NS that another organizes female Mus lumbar injection isodose is matched group.The filial mice that the female Mus of model group gives birth to is designated as VPA autism model mouse (VPA group); The filial mice that the female Mus of matched group gives birth to is designated as Normal group (Control group).Filial mice is (Postnatal day, PND) ablactation in 23 days after birth.VPA group filial mice and Control group filial mice are got respectively 6～15 and carry out subsequent experimental research.
Test the impact of 1 variable concentrations VPA on former culture neuron GSK-3 β and β-catenin.
VPA(0 with variable concentrations, 1mM, 5mM, 10mM) process former culture neuron 24h, adopt Western blot(molecular engram) method measures the expression of GSK-3 β (GSK-3) and β-catenin albumen (beta chain albumen) in neuronal cell.Result demonstration, β-catenin protein expression is in 5mM and 10mM processed group and the obvious rising of matched group, and difference has remarkable statistical significance (Figure 1A).And then the expression of the negativity regulatory factor GSK-3 β that has detected β-catenin under variable concentrations.Result shows, 1mM, and 5mM and 10mM processed group are compared with matched group, and GSK-3 β protein expression is all lowered, and still, 5mM and 10mM processed group and matched group are significantly lowered (Figure 1B).Below experiment is just processed former culture neuron with the VPA of 5mM as ideal concentration.
The acid treatment of experiment 2N-mucolyticum has reduced the former culture neuron oxidative stress level that VPA processes.
With VPA(5mM) culture medium that more renews after pretreatment primary neuron 24h, add antioxidant 1mM NAC(N-acetylcysteine), continue collecting cell after cultured cell 1h.Use Western blot technology for detection oxidative stress mark 4-HNE(4-hydroxyl nonenyl aldehyde) variation, use FACS(Flow Cytometry) method detects the situation of change of ROS.Result shows, compares with matched group, and VPA processes the expression that obviously increases 4-HNE, and difference has the statistical significance (Fig. 2) of highly significant; Compare with VPA processed group, NAC processed group 4-HNE expresses obviously and lowers, and difference has significant statistical significance (Fig. 2); Compare with VPA processed group, VPA and NAC coprocessing group 4-HNE down-regulated expression, difference has statistical significance (Fig. 2).Streaming result shows, compares with matched group, and VPA processes the expression that significantly increases ROS, and difference has the statistical significance (Fig. 3) of highly significant; Compare with VPA processed group, NAC processed group and VPA+NAC processed group all significantly reduce the expression of ROS, and difference has the statistical significance (Fig. 3) of highly significant.
The acid treatment of experiment 3N-mucolyticum does not change the former culture neuron classical Wnt level that VPA processes.
Real-time found that, compares with matched group, and VPA processes and obviously raised β-catenin mrna expression, has lowered the expression of GSK-3 β mRNA, and difference has statistical significance (Fig. 4 A, B).VPA+NAC processed group is compared with VPA processed group, and matched group is compared with NAC processed group, and GSK-3 β, β-catenin mrna expression level are all less than variation, difference not statistically significant (Fig. 4 A, B).
With VPA(5mM) culture medium that more renews after pretreatment primary neuron 24h, add the sulindac (Sulindac) (0,1mM, 3mM, 5mM) of variable concentrations, continue collecting cell after cultured cell 1h.Adopting Real-time PCR(fluorescent PCR at regular time and quantity) method measures the expression of β-catenin mRNA in neuronal cell.Result shows, β-catenin mrna expression is relatively lowered in 3mM and 5mM processed group and matched group, and difference has statistical significance (Fig. 5).Experiment subsequently is just processed former culture neuron with 3mM sulindac as ideal concentration.Western blot result of study is found, compare with matched group, VPA processes the expression of obviously having lowered GSK-3 β, raised the P-GSK-3 β (the GSK-3 β of phosphorylation) of inhibition, raised the expression of β-catenin, lowered the β-catenin of P-β-catenin(phosphorylation of inhibition), difference has the statistical significance (Fig. 6 A, B) of highly significant; Compare with VPA processed group, VPA+ sulindac processed group has obviously been lowered the P-GSK-3 β of inhibition, has raised the P-β-catenin of inhibition, and difference has the statistical significance (Fig. 6 A, B) of highly significant.
Experiment subsequently detected sulindac process rear oxidation stress variation.Compare with matched group, VPA group has increased the expression of 4-HNE, and difference has statistical significance (Fig. 7).Compare with VPA group, VPA and sulindac coprocessing have reduced the expression of 4-HNE, and difference has significant statistical significance (Fig. 7).
Test 6 sulindacs VPA autism animal model is repeated to slow-witted sample behavioral implications.
Adopt open field test to detect the stiff sample behavior that repeats of three groups of rat offspring rats.Result shows, compare with matched group, VPA group is in 0～5min and 20～25min hyperactivity, and VPA group is at 0～5min in addition, 5～10min, 10～5min repeats stiff sample behavior number of times obviously to be increased, difference has statistical significance (Fig. 9 A, B), compares with VPA group, and VPA and sulindac while processed group are at 0～5min, 5～10min, 10～15min activity weakens (Fig. 9 A, B).Meanwhile, rat oneself reason hair and upright behavior have been detected.Compare with matched group, VPA organizes the self-grooming time obviously increases (Fig. 8 A), and upright behavior number of times obviously increases (Fig. 8 B).And compare with VPA group, VPA and sulindac be processed group oneself's grooming time and upright behavior number of times minimizing (Fig. 8 A, B) simultaneously.Compare with matched group, VPA and processed group oneself's grooming time sulindac while and upright behavior number of times do not have significant difference (Fig. 8 A, B).
The application of sulindac aspect the medicine of preparation treatment Social behaviors obstacle.
Laboratory animal and VPA(sodium valproate) autism Animal Model is with embodiment 1.
Test 7 sulindacs to the behavioral implications of VPA autism animal model Social Interaction.
Use the impact of animal society's interbehavior test sulindac on autism model mouse Social behaviors.Social Interaction behavioral indicator adopts experimental rat to enter the time of fresh target place case and new rat place case and time two indexs that experimental rat is smelt fresh target and new rat.Rat is entered to the comparison of the number of times of left case and right case, result demonstration, three groups do not have significant difference (Figure 10 C), so just exclude the impact on experimental result on case preference of three groups of rats.In matched group and VPA and sulindac while processed group, enter into the time of new rat place case higher than the time at fresh target place case, difference has statistical significance (Figure 10 A); In VPA group, in the time of new rat place case and fresh target place case, there is no significant difference (Figure 10 A).In addition, in matched group and VPA and sulindac while processed group, smell the time of new rat higher than the time of smelling fresh target place, difference has significant statistical significance (Figure 10 B); In VPA group, the time of smelling new rat does not have significant difference (Figure 10 B) with the time of smelling fresh target.
Result demonstration, sulindac can reduce the GSK-3 β phosphorylation of inactivation, increases β-catenin phosphorylation of inhibition, thus it is active to lower classical Wnt signal path; And reduce the generation of 4-HNE and ROS, reduce oxidative stress; Spacious experimental result shows, VPA autism animal model repeat stiff sample behavior VPA and sulindac while processed group be improved significantly; The demonstration of Social Interaction experimental result, sulindac has improved the defect of the Social Interaction behavior of VPA autism animal model.Experiment is also observed, and after former culture neuron activates classical Wnt signal path with VPA, sulindac is processed the generation that has reduced 4-HNE and ROS when reducing classical Wnt signal path; And antioxidant NAC processing has reduced 4-HNE and ROS produces, but the expression of do not change GSK-3 β and β-catenin.These presentation of results: sulindac has antioxidant properties, and its antioxidant properties is relevant with downward classical Wnt signal path activity; Sulindac can reduce the stiff sample dystropy that repeats of autism sample, improves the Social behaviors obstacle of autism sample, can be used for preparing the medicine of the stiff limitation for the treatment of behavior, the medicine of preparation treatment Social behaviors obstacle, and then for the preparation of the autistic medicine for the treatment of.
Claims (4)
1. the application of sulindac aspect the autistic medicine of preparation treatment.
2. the application aspect the medicine that sulindac postpones at preparation treatment development of speech.
3. the application of sulindac aspect the medicine of preparation treatment Social behaviors obstacle.
4. sulindac is in the application of preparing aspect the medicine of the stiff limitation for the treatment of behavior.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108355135A (en) * | 2018-04-19 | 2018-08-03 | 新乡医学院 | Notch signal pathway inhibitors are preparing the application in treating lonely disease drug |
| US20190314308A1 (en) * | 2018-04-13 | 2019-10-17 | Healx Limited | Treatment of fragile x syndrome |
| CN111690732A (en) * | 2020-06-05 | 2020-09-22 | 南通大学 | Application of GSK-3 beta as blood marker in preparation of mental disorder early diagnosis reagent |
| CN113040090A (en) * | 2021-04-13 | 2021-06-29 | 南京医科大学 | Method for constructing animal model of autism and corresponding application |
| US11590093B2 (en) | 2018-04-13 | 2023-02-28 | Healx Limited | Kit, composition, and combination therapy for fragile X syndrome |
-
2013
- 2013-12-16 CN CN201310693076.2A patent/CN103622941A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| YINGHUA ZHANG,ET AL.: "Downregulating the Canonical Wnt/b-catenin Signaling Pathway Attenuates the Susceptibility to Autism-like Phenotypes by Decreasing Oxidative Stress", 《NEUROCHEM RES》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20190314308A1 (en) * | 2018-04-13 | 2019-10-17 | Healx Limited | Treatment of fragile x syndrome |
| CN112055587A (en) * | 2018-04-13 | 2020-12-08 | Healx有限公司 | Treatment of fragile X syndrome |
| US10864182B2 (en) * | 2018-04-13 | 2020-12-15 | Healx Limited | Treatment of fragile X syndrome |
| US11590093B2 (en) | 2018-04-13 | 2023-02-28 | Healx Limited | Kit, composition, and combination therapy for fragile X syndrome |
| CN108355135A (en) * | 2018-04-19 | 2018-08-03 | 新乡医学院 | Notch signal pathway inhibitors are preparing the application in treating lonely disease drug |
| CN108355135B (en) * | 2018-04-19 | 2020-07-07 | 新乡医学院 | Application of Notch signal pathway inhibitor in preparation of drug for treating autism |
| CN111690732A (en) * | 2020-06-05 | 2020-09-22 | 南通大学 | Application of GSK-3 beta as blood marker in preparation of mental disorder early diagnosis reagent |
| CN111690732B (en) * | 2020-06-05 | 2023-04-28 | 南通大学 | Application of GSK-3 beta as blood marker in preparation of mental disorder early diagnosis reagent |
| CN113040090A (en) * | 2021-04-13 | 2021-06-29 | 南京医科大学 | Method for constructing animal model of autism and corresponding application |
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