CN103622940A - Application of gossypol acetate in pharmacy - Google Patents

Application of gossypol acetate in pharmacy Download PDF

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CN103622940A
CN103622940A CN201310547165.6A CN201310547165A CN103622940A CN 103622940 A CN103622940 A CN 103622940A CN 201310547165 A CN201310547165 A CN 201310547165A CN 103622940 A CN103622940 A CN 103622940A
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gossypol acetate
medicine
syndrome
mecp2
application
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CN103622940B (en
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王晓英
胡克平
王程程
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Institute of Medicinal Plant Development of CAMS and PUMC
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Institute of Medicinal Plant Development of CAMS and PUMC
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Abstract

The invention discloses a novel application of gossypol acetate in the field of pharmacy, and in particular relates to an application of gossypol acetate in preparing medicines for preventing, relieving and/or treating reye's syndrome, and belongs to the field of pharmacy. Reye's syndrome is a cryptogenic acute encephalopathy syndrome in the childhood phase, and studies discover that loss or mutation of MeCP2 gene has a direct causal relationship with the reye's syndrome, and loss of the MeCP2 gene can cause reye's syndrome developing on a mouse. Experiments indicate that the content of the MeCP2 gene in the brain of a rat can be remarkably increased by administrating the rat with gossypol acetate, so that the content of the MeCP2 gene in the brain of a patient can be remarkably increased by using the gossypol acetate for preventing, relieving and treating the reye's syndrome caused by MeCP2 mutation, the development of the nerve cell of the patient can be promoted, functions of the nervous system can be restored, and the possibility of healing the patient can be increased. Therefore, according to the application of the gossypol acetate in preparing the medicine for resisting reye's syndrome, the medicine can be used for preventing, relieving and/or treating the reye's syndrome.

Description

The application of gossypol acetate in pharmacy
Technical field
The present invention relates to gossypol acetate in the application of pharmaceutical field, the particularly application of gossypol acetate in the anti-thunder syndrome medicine of preparation.
Background technology
Thunder syndrome is a kind of neurodevelopment infantile autism pedigree obstacle (autism spectrum disorder) of serious X-linkage, be domestic and international generally acknowledged MeCP2(methyl CpG – binding protein2, methylated CpG is in conjunction with albumen 2) the pathogenic disease of single-gene.Between the loss of research discovery MeCP2 gene or sudden change and thunder syndrome, there is direct cause effect relation, for thunder syndrome provides potential treatment target.The research of thunder syndrome mouse model is found, the recovery of its MeCP2 function can make the neurological symptoms result of adult mice reverse, and makes thunder syndrome patient have the possibility of curing.
Gossypol acetate is a kind of polyhydric phenols with extensive pharmacological action extracting in Malvaceae plant cotton, tree cotton or Gossypium hirsutum L. mature seed, root bark, has the effects such as antifertility, anti-inflammatory, antiviral, and its chemical structural formula is as follows:
Figure BDA0000409529570000011
Prior art by refining gossypol acetate with the dosage of 20mg/ days as man's birth control medicine, reduced significantly the survival rate of sperm; Clinical research finds that gossypol acetate also has obvious inhibitory action to gynaecopathias such as the tumor of men and women's reproductive system, endometriosis.
In realizing process of the present invention, inventor finds that prior art at least exists following problem:
The research of prior art Dichlorodiphenyl Acetate gossypol purposes mainly concentrates on the gynaecopathia aspects such as the tumor, endometriosis for the treatment of men and women reproductive system, not yet finds its application in thunder syndrome medicine of preparation treatment MeCP2 sudden change.
Summary of the invention
In order to solve prior art gossypol acetate range of application, be confined to the problem of oncotherapy, the object of the present invention is to provide the new purposes of gossypol acetate in pharmacy, the concrete technical scheme that realizes this object is as follows:
The embodiment of the present invention provides the application of gossypol acetate in the medicine of preparation prevention, alleviation and/or treatment thunder syndrome.
The experimental result of the solution of technical scheme of the present invention based on following: the embodiment of the present invention is passed through pharmacological experiment, give Oral Administration in Rats gossypol acetate, then respectively blank group and gossypol acetate group are carried out to western-blot(western blotting) and SABC mensuration, and the western-blot that obtains respectively blank group and gossypol acetate group schemes and ImmunohistochemistryResults Results schematic diagram, as seen from the figure: gossypol acetate group is compared with blank group, and the content of the MeCP2 in rat whole brain improves significantly; The content of MeCP2 in rat layer is also significantly improved.Visible gossypol acetate can significantly improve the content of MeCP2 in rat brain, be the content that gossypol acetate can significantly improve MeCP2 gene in rat brain, promote the neuronic growth of patient, thereby its neural function is restored, increase the probability that patient cures.Hence one can see that, and gossypol acetate can be for the preparation of the thunder syndrome medicine of anti-MeCP2 sudden change.
Particularly, the gossypol acetate that the medicine of described prevention, alleviation and/or treatment thunder syndrome is prevention or treatment effective dose, wherein gossypol acetate is separately as the active component in medicine.
Particularly, the pharmaceutical pack of described prevention, alleviation and/or treatment thunder syndrome containing the gossypol acetate of prevention or treatment effective dose, with other medicine classes of gossypol acetate compatibility and optional pharmaceutically acceptable carrier and/or adjuvant, alternatively, gossypol acetate wherein also can be prepared into the derivant of the clinical acceptable medicine relevant with its pharmacology.
The dosage form of the medicine of described prevention particularly,, alleviation and/or treatment thunder syndrome is selected from solution, suspension agent, Emulsion, pill, capsule, powder agent, Controlled release formulation and extended release preparation.
The administering mode of the medicine of described prevention particularly,, alleviation and/or treatment thunder syndrome is selected from oral administration, nose administration, parenteral or rectally, canalis spinalis administration, intravenous injection, intramuscular injection, subcutaneous injection.
The beneficial effect that the technical scheme that the embodiment of the present invention provides is brought is:
The embodiment of the present invention provides gossypol acetate new application in pharmacy, by by gossypol acetate for the preparation of prevention, alleviate and the medicine of the thunder syndrome that treatment is caused by MeCP2 sudden change in, make this medicine can obviously increase the content of MeCP2 gene in brain in patients, promote the neuronic growth of patient, thereby its neural function is restored, increases the probability that patient cures.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing of required use during embodiment is described is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skills, do not paying under the prerequisite of creative work, can also obtain according to these accompanying drawings other accompanying drawing.
Fig. 1 a and Fig. 1 b are respectively in the rat whole brain that provides of the embodiment of the present invention one, the western-blot(Western blotting of gossypol acetate group and blank group) qualitative figure and quantitative figure;
Fig. 2 a and Fig. 2 b are respectively in the rat cerebral cortex that provides of the embodiment of the present invention one, the western-blot(Western blotting of gossypol acetate group and blank group) qualitative figure and quantitative figure;
Fig. 3 is the MeCP2 dyeing ImmunohistochemistryResults Results schematic diagram of the gossypol acetate group cortex that provides of the embodiment of the present invention two;
Fig. 4 is the MeCP2 dyeing ImmunohistochemistryResults Results schematic diagram of the blank group cortex that provides of the embodiment of the present invention two;
Fig. 5 is the ImmunohistochemistryResults Results schematic diagram of the blank group that provides of the embodiment of the present invention two.
Wherein, the blank group of A;
B gossypol acetate group;
C?MeCP2;
D actin;
E MeCP2/ β actin relative expression quantity (take blank group as benchmark).
The specific embodiment
For making the object, technical solutions and advantages of the present invention clearer, below in conjunction with accompanying drawing, embodiment of the present invention is described further in detail.
Embodiment of the present invention instrument equipment and raw material are as follows:
Instrument and equipment:
MQX200 microplate reader (BioTek, the U.S.);
JY92-II DN ultrasonic cell disruptor (NingBo XinZhi Biology Science Co., Ltd);
EPS-300 electrophresis apparatus (Shanghai Tian Neng Science and Technology Ltd.);
VE-180 Vertial electrophorestic tank (Shanghai Tian Neng Science and Technology Ltd.);
VE-186 electrophoretic blotting groove (Shanghai Tian Neng Science and Technology Ltd.);
ChemiDox XRS gel imaging system (BIO-RAD, the U.S.);
K30 dry-type thermostat (Hangzhou Ao Sheng Instrument Ltd.);
PE20 laboratory pH meter (the limited public company of prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit instrument (Shanghai));
AL104-IC electronic balance (the limited public company of prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit instrument (Shanghai));
BX53 system microscope (OLYMPUS(Olympus), Japan);
BT100-2J peristaltic pump (Baoding LanGe constant flow pump Co., Ltd);
RM2245 paraffin slicing machine (Leica, Germany).
Raw material:
Gossypol acetate: purchased from middle cotton purple light biotechnology company, outward appearance: yellow or buff powder, CAS No:12542-36-8, specification: 98%(high performance liquid chromatogram detects);
Ripa buffer(buffer): use distilled water to dissolve 0.6055g Tris(Tris), 0.8766g NaCl, 1ml NP-40(Nonidet P40), 0.5g NaTDC and 0.1g SDS(sodium lauryl sulphate), and be settled to 100ml with distilled water;
100mM PMSF(Phenylmethanesulfonyl fluoride, mM is mmol/L): 0.174g PMSF is dissolved in 10ml isopropyl alcohol, subpackage ,-20 ℃ of storages, the ratio with PMSF:Ripa buffer=1:100 during use adds in Ripa buffer;
100mM DTT(dithiothreitol, DTT): 0.154gDTT is dissolved in 10ml distilled water, subpackage ,-20 ℃ of storages, the ratio of used time with DTT:Ripa buffer=1:100 adds in Ripa buffer;
Electrophoretic buffer: use distilled water to dissolve 3.03gTris, 18.77g glycine and 1.0g SDS, and be settled to 1000ml with distilled water;
30%Acr/Bis(29:1) solution (acrylamide/methylene diacrylamide): use distilled water to dissolve 29g acrylamide and 1g methylene diacrylamide, and be settled to 100ml with distilled water, keep in Dark Place at 4 ℃;
Separation gel buffer: use distilled water to dissolve 18.165g Tris, adjust pH to 8.8, and be settled to 100ml with distilled water;
Concentrated glue buffer: use distilled water to dissolve 12.11g Tris, adjust pH to 6.8, and be settled to 100ml with distilled water;
10%SDS: use distilled water to dissolve 10g SDS, and be settled to 100ml with distilled water;
10% Ammonium persulfate.: by 0.1g Ammonium persulfate., add in 0.1ml distilled water and dissolve, subpackage, preserves 1 week for 4 ℃, preserves January for-20 ℃;
Electricity turns buffer: use distilled water to dissolve 3.03g Tirs, and 14.41g glycine, 200ml methanol, and be settled to 1000ml with distilled water;
TBS buffer: use distilled water to dissolve 6.055g Tris, 8.766g NaCl, adjusts pH to 7.5, and be settled to 1000ml with distilled water;
In TBS-T:TBS buffer, add 0.04% Tween-20(tween 20);
Confining liquid: containing the TBS-T solution of 5% defatted milk powder;
Ponceaux dye liquor: use distilled water to dissolve 0.2g Ponceau S, 3g sulfosalicylic acid and 3g trichloroacetic acid, and be settled to 100ml with distilled water;
PBS buffer (Phosphate Buffer Solution: phosphate buffer): use distilled water to dissolve 8g sodium chloride (NaCl), 0.2g potassium chloride (KCl), 1.44g sodium hydrogen phosphate (Na2HPO4), 0.24g potassium dihydrogen phosphate (KH2PO4), adjust pH to 7.4, and be settled to 1000ml with distilled water;
ABC SABC test kit: purchased from Wuhan doctor's moral company limited, model: SA1022, specification: 1/2KIT;
DAB colour reagent box: purchased from Le Bo biotech firm, model: AR1022.
Embodiment mono-: western-blot(western blotting) measure the impact of gossypol acetate on Mecp2 content in rat brain
The embodiment of the present invention is taked western-blot(Western blotting) method, determined the variation of the content of Mecp2 in rat brain, concrete steps are as follows:
Get 56 8 weeks large male SPF level (Specefic pathogen Free, no-special pathogen) wistar(rat), be divided at random 2 groups: blank group (giving edible oil and distilled water), gossypol acetate group (give gossypol acetate 50mg/kg and distilled water, now 50mg/kg to refer to the single dose that gives every kilogram of rat be 50mg).By above-mentioned rat sub-cage rearing, ad lib drinking-water, keeps 25 ± 1 ℃ of indoor temperatures, relative humidity 55 ± 5%, the illumination of 12h illumination/12h dark cycle.Administering mode is oral administration, and except blank group, Dichlorodiphenyl Acetate gossypol group is carried out modeling, successive administration two weeks in medicine feed mode once every other day.Above-mentioned 2 groups of rats are put to death respectively after two weeks sub-cage rearings, draw materials.
The process of drawing materials:
Above-mentioned rat is after two weeks sub-cage rearings, and the chloral hydrate with 10% (W/V) is anaesthetized, and the ratio that anesthesia amount gives 0.3-0.4ml injection volume in every 100g rat is determined.The above-mentioned rat broken end of respectively organizing of having anaesthetized is got to brain, and isolate complete brain, then brain is separated into cortical tissue, hippocampal tissue and appurtenance, uses immediately dry ice freezing, and by blank group and gossypol acetate group, be put in respectively-80 ℃ of refrigerators and preserve to complete and draw materials.
Sample preparation:
(1) cut respectively the freezing rat layer tissue of appropriate above-mentioned rat and brain whole brain tissue (cortical tissue, hippocampal tissue and appendicular mixture) on ice, weigh;
(2) to the Ripa buffer lysate (containing DTT, PMSF) that adds respectively 10 times of volumes in above-mentioned cerebral cortex sample of weighing and the full brain sample of brain, with ultrasonic (the work 2s of ultrasonic cell disintegration instrument, 3s intermittently, power 125W, omnidistance 3min) prepare tissue homogenate;
(3) homogenate is hatched 30min on ice;
(4) homogenate is with 12000rpm centrifugal 10min at 4 ℃;
(5) after centrifugal, abandon precipitation and get supernatant, be the full brain sample of cerebral cortex sample to be measured and brain;
(6) BCA (acid of bicinchonininc acid dihomocinchonine) method is measured cerebral cortex sample to be measured and the full brain sample of brain total protein concentration;
(7) utilize SDS sample-loading buffer, above-mentioned cerebral cortex sample and the full brain sample protein of brain concentration are adjusted to isoconcentration;
(8) above-mentioned cerebral cortex sample and the full brain sample of brain are carried out to degeneration with 98 ℃ of heating 3min of dry-type thermostat, be cooled to room temperature standby.
Denaturing polyacrylamide gel electrophoresis:
(1) by 10% SDS-PAGE(sodium dodecyl sulfate polyacrylamide gel electrophoresis: polyacrylamide gel electrophoresis) separation gel is fully mixed evenly, poured in preprepared glue plate, water seal, room temperature is placed 30-60min and is solidified (separation gel and water intersection can be seen a straight line clearly) to separation gel;
(2) after gelling to be separated admittedly, water is outwelled, with absorbent paper, blotted, plug loading comb, the concentrated glue of 5% SDS-PAGE is filled with in loading comb, get rid of bubble, the extremely concentrated gelling of standing 15-30min is solid.
(3) respectively the ready cerebral cortex sample of sample preparation steps and the full brain sample of brain are added in gel pore gently;
(4) electrophresis apparatus is arranged to voltage stabilizing state, is adjusted to 70V~40min, after above-mentioned each sample enters separation gel, be adjusted to 140V~90min and carry out electrophoresis;
(5) when bromophenol blue indicatrix is about to plastic emitting, stop electrophoresis, prepare transferring film.
Transferring film:
(1) by plastic stent, foam-rubber cushion, filter paper, PVDF(Polyvinylidene Fluoride: polyvinylidene fluoride) film etc. turns balance 5min(PVDF film in liquid at electricity and need soak into through 100% methanol);
(2), after electrophoresis finishes, plastic stent keeps flat (black-film under), places successively foam-rubber cushion, 2 bed thickness filter paper, gel, transfer film, 2 bed thickness filter paper, foam-rubber cushion, and drives each interlayer bubble away, clips support, puts into electrophoresis transferring groove;
(3) electrophresis apparatus is arranged to current stabilization state, is adjusted to 200mA~90min, in ice bath, carry out electricity and turn;
(4) electricity turns after end, takes out film and carries out labelling, and with the dyeing of Ponceaux dye liquor, methanol decolouring, to only visible protein band, is observed transfer effect, and film is suitably cut out to standby one-tenth transfer film.
Antigen antibody reaction:
(1) transfer film is put into confining liquid, seal at 4 ℃ and spend the night;
(2) transfer film having sealed is put into hybridization bag, by the size of film, add the primary antibodie (anti-MeCP2 antibody) of appropriate confining liquid dilution, eliminate bubble sealing, 4 ℃ of overnight incubation.
(3) take out transfer film, use TBS-T solution washing three times, each 10min;
(4) film is put into hybridization bag, adds HRP(horseradish peroxidase) corresponding two anti-(rabbit anti-mouse igg two of HRP combination is anti-) of labelling, eliminate bubble sealing, room temperature oscillation incubation 2h.
(5) take out transfer film, use TBS-T solution washing three times, each 10min.
Chromogenic reaction:
(1) get A liquid and the B liquid (A liquid is luminol (Luminol) and special luminescence enhancer, and B liquid is stabilizer of hydrogen peroxide) of ECL electrogenerated chemiluminescence reagent, even by 1:1 volume mixture;
(2) transfer membrane of hatching is put into the plate of suitable size, got ECL mixed liquor and be added on transfer film, film is contacted with uniform liquid, lucifuge reaction 5min;
(3) transfer film is put into gel imaging system and exposed it is carried out to qualitative analysis, and with Image J software, slice result is carried out to semi-quantitative analysis, obtain the western-blot figure of rat cerebral cortex and the full brain of brain.
The western-blot that the embodiment of the present invention has been carried out test to blank group and gossypol acetate group respectively by said method and obtained respectively blank group and gossypol acetate group schemes, from Fig. 1 a and Fig. 1 b: gossypol acetate group is compared with blank group, and the content of the MeCP2 in rat whole brain improves significantly; From Fig. 2 a and Fig. 2 b: gossypol acetate group is compared with blank group, and the content of the MeCP2 in rat layer is also significantly improved; Visible, gossypol acetate can significantly improve the content of MeCP2 in rat brain.Embodiment of the present invention experiment shows, by by gossypol acetate to rat administration, can obviously increase the content of MeCP2 gene in rat brain, hence one can see that, gossypol acetate, for preventing, alleviate and treat the thunder syndrome being caused by MeCP2 sudden change, can obviously be increased to the content of brain in patients MeCP2 gene, promote the neuronic growth of patient, thereby its neural function is restored, increases the probability that patient cures.Therefore, the application of gossypol acetate in the anti-thunder syndrome medicine of preparation, makes this medicine can be used for prevention, alleviate and/or treatment thunder syndrome.
Embodiment bis-: SABC algoscopy is measured the impact of gossypol acetate on Mecp2 content in rat brain
Get 56 8 weeks large male SPF level (Specefic pathogen Free, no-special pathogen) wistar(rat), be divided at random 2 groups: blank group (giving edible oil and distilled water), gossypol acetate group (gives gossypol acetate 50mg/kg and distilled water, now 50mg/kg to refer to the single dose that gives every kilogram of rat be 50mg), by above-mentioned rat sub-cage rearing, ad lib drinking-water, keeps 25 ± 1 ℃ of indoor temperatures, relative humidity 55 ± 5%, the illumination of 12h illumination/12h dark cycle.Administering mode is oral administration, and except blank group, Dichlorodiphenyl Acetate gossypol group is carried out modeling, successive administration two weeks in medicine feed mode once every other day.Above-mentioned 2 groups of rats are put to death respectively after two weeks sub-cage rearings, draw materials.
The process of drawing materials:
First the rat of above-mentioned grouping is carried out to 4% paraformaldehyde perfusion, and after administration 2h, with 10% chloral hydrate (W/V), anaesthetize, the ratio that anesthesia amount gives 0.3-0.4ml injection volume in every 100g rat is determined.By what anaesthetized, above-mentionedly respectively organize rat and cut off successively skin, thoracic cavity, fully exposes heart, cuts off left side apex, from left ventricle, with perfusion syringe needle, towards aorta direction, inserts, and to fixing in aorta, hemostasis clamp closes.First with the quick perfusion of PBS buffer, at left auricle, cut and allow flatly blood and perfusate flow out, treat that effluent starts to bleach, change with 4% paraformaldehyde liquid, continue perfusion 10min left and right, take out rat whole brain, be placed in 4% paraformaldehyde, spend the night, second day is cut and is repaired Hippocampus place crown with blade, continues fixedly 24h.Cerebral tissue takes out in sucrose fixative, distilled water flushing 3 times, of thermostat slicer freezer, make the section of 5 μ m transverse section, section is mounted on micro slide, then following each time period of dehydration of alcohols at different levels: 50% ethanol (2min) → 70% ethanol (2min) → 80% ethanol (2min) → 95% ethanol (2min) → 100% ethanol (2min), then the section after dehydration is placed at-20 ℃, preserve stand-by.Transparent with dimethylbenzene again, piece of tissue is put into fritting state cake wax, fully infiltrates, and tangent plane is carried out to embedding down.Slice thickness 5 μ m, be affixed on and scribble APES(3-aminopropyl-3-(ethoxymethyl) silane) on the slide of anticreep tablet, put on hot plate and make its extended flat with a small amount of water, slide is continued to be placed on hot plate and bake to completely dry, be then placed in 370C baking box baking 6h and can complete and draw materials and obtain print.
Dewaxing and aquation:
(1) dimethylbenzene I 30min, dimethylbenzene II 30min.
(2) 100% ethanol I, II, 95% ethanol I, II, 80% ethanol is respectively carried and being inserted 10 times.
(3) distilled water is washed twice
Antigen retrieval:
Adopt Microwave method method,
(1) the PBS buffer of 0.01M is developed a film, 5min * 3 time;
(2) 3% H 2o 2lucifuge incubated at room 1h;
(3) the PBS buffer of 0.01M is developed a film, 5min * 3 time;
(4) citrate buffer of 0.01M, high fiery 2min in microwave oven, low fiery 5min, dries in the air cool;
(5) the PBS buffer of 0.01M is developed a film, 5min * 3 time;
(6) antigen retrieval liquid (citrate buffer) lucifuge incubated at room 10min;
(7) the PBS buffer of 0.01M is developed a film, 5min.
Antibody incubation:
(1) 5%BSA (Bovine Serum Albumin: bovine serum albumin) room temperature sealing 1h;
(2) drip primary antibodie (anti-Mecp2 antibody), 4 ℃ of 16h, incubated at room 30min, hatches 30min for 37 ℃;
(3) the PBS buffer of 0.01M is developed a film, 5min * 3 time;
(4) drip two anti-(rabbit anti-mouse igg two of HRP combination is anti-, ABC SABC test kit), hatch 1h for 37 ℃;
(5) 0.01MPBS buffer is developed a film, 5min * 3 time;
Development dyeing (SABC(SABC) method):
(1) drip SABC(oxide enzyme), hatch 30min for 37 ℃;
(2) 0.01MPBS buffer is developed a film, 5min * 3 time;
(3) DAB colour developing 5-10min(DAB colour reagent box), the reaction of distilled water color development stopping, this process is controlled developing time under the microscope;
(4) 95% ethanol I, each 3min of II, 100% ethanol I, II, each 5min of III;
(5) dimethylbenzene I, II, each 10min of III;
(6) resinene mounting.
The embodiment of the present invention by said method respectively the MeCP2 of the rat sample cortex of Dichlorodiphenyl Acetate gossypol group, blank group and blank group carried out SABC mensuration.Wherein (gossypol acetate group adds MeCP2 primary antibodie to the MeCP2 colored graph of gossypol acetate group cortex, in figure, brown granule represents MeCP2 albumen) as shown in Figure 3, (blank group adds MeCP2 primary antibodie to the MeCP2 colored graph of blank group cortex, in figure, brown granule represents MeCP2 albumen) as shown in Figure 4, the ImmunohistochemistryResults Results schematic diagram of blank group (blank group does not add MeCP2 primary antibodie) is as shown in Figure 5.
From Fig. 3 and Fig. 4, gossypol acetate administration group adds the MeCP2 colored graph of the gossypol acetate group cortex after MeCP2 primary antibodie to compare with adding the MeCP2 colored graph of the blank group cortex after MeCP2 primary antibodie, wherein the quantity of MeCP2 albumen (being brown particle) is significantly increased, in addition, as shown in Figure 5, do not add the existence that MeCP2 albumen substantially do not detected in the blank group ImmunohistochemistryResults Results schematic diagram of MeCP2 primary antibodie, utilize gossypol acetate administration to increase significantly the content of MeCP2 in rat brain as seen, be the content that gossypol acetate can significantly improve MeCP2 gene in rat brain.
Embodiment of the present invention experiment shows, by by gossypol acetate to rat administration, can obviously increase the content of MeCP2 gene in rat brain, hence one can see that, gossypol acetate, for preventing, alleviate and treat the thunder syndrome being caused by MeCP2 sudden change, can obviously be increased to the content of brain in patients MeCP2 gene, promote the neuronic growth of patient, thereby its neural function is restored, increases the probability that patient cures.Therefore, the application of gossypol acetate in the anti-thunder syndrome medicine of preparation, makes this medicine can be used for prevention, alleviate and/or treatment thunder syndrome.
The foregoing is only preferred embodiment of the present invention, in order to limit the present invention, within the spirit and principles in the present invention not all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.

Claims (5)

1. the application of gossypol acetate in preparation prevention, alleviation and/or treatment thunder syndrome medicine.
2. the application of gossypol acetate according to claim 1 in preparation prevention, alleviation and/or treatment thunder syndrome medicine, is characterized in that, described medicine is the gossypol acetate of prevention or treatment effective dose.
3. the application of gossypol acetate according to claim 1 in preparation prevention, alleviation and/or treatment thunder syndrome medicine, it is characterized in that, described pharmaceutical pack containing the gossypol acetate of prevention or treatment effective dose, with other medicine classes of gossypol acetate compatibility and optional pharmaceutically acceptable carrier and/or adjuvant.
4. the application in preparation prevention, alleviation and/or treatment thunder syndrome medicine according to the gossypol acetate described in claim 1-3 any one, it is characterized in that, the dosage form of described medicine is selected from tablet, solution, suspension agent, Emulsion, pill, capsule, powder agent, Controlled release formulation and extended release preparation.
5. the application in preparation prevention, alleviation and/or treatment thunder syndrome medicine according to the gossypol acetate described in claim 1-3 any one, it is characterized in that, the administering mode of described medicine is selected from oral administration, nose administration, parenteral or rectally, canalis spinalis administration, intravenous injection, intramuscular injection, subcutaneous injection.
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CN109908119A (en) * 2019-04-25 2019-06-21 中国科学院化学研究所 The agent of LRPPRC negative regulation and purposes
CN114377053A (en) * 2022-01-18 2022-04-22 云南贝泰妮生物科技集团股份有限公司 Cooling gel dressing and preparation method thereof
WO2022166933A1 (en) * 2021-02-05 2022-08-11 上海科技大学 Anti-coronavirus application of compound

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