CN106389465B - The application of astaxanthin and/or lithium chloride in the drug that preparation prevents and treats cognitive disorder illness caused by chronic organophosphorus poisoning - Google Patents
The application of astaxanthin and/or lithium chloride in the drug that preparation prevents and treats cognitive disorder illness caused by chronic organophosphorus poisoning Download PDFInfo
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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Abstract
The present invention provides the application of astaxanthin and/or lithium chloride in the drug that preparation prevents and treats cognitive disorder illness caused by chronic organophosphorus poisoning.Use in conjunction astaxanthin of the present invention and lithium chloride inhibitor, the therapeutic effect that astaxanthin group is relatively used alone become apparent, and the phosphorylation level of Akt/GSK3 β/CREB signaling pathway protein is significantly improved compared with model group in mouse brain.Therefore, the treatment of astaxanthin joint lithium chloride has significant neuroprotection that is anti-oxidant, inhibiting apoptosis, so as to improve the cognitive function of OPS poisoning mice.Astaxanthin provided by the invention and lithium chloride use in conjunction can have neuroprotection to Hippocampal Injury caused by chronic organophosphorus poisoning; and cognition dysfunction caused by chronic organophosphorus poisoning is improved by activation Akt/GSK3 β/CREB signal path, show that the therapeutic reagent is expected to the prospect of cognitive disorder drug caused by developing into the novel chronic organophosphorus poisoning of prevention and treatment.
Description
Technical field
The invention belongs to drug fields, and in particular to astaxanthin and/or lithium chloride are chronic organic in preparation prevention and treatment
Application in the drug of cognitive disorder illness caused by phosphorism.
Background technique
Organophosphorus pesticide (organophosphate pesticides, OPS) is widely used in current world wide
Insecticide, have insecticidal spectrum is wide, drug effect is high, lower-price characteristic, be widely used in family and agricultural the anti-evil of insect prevention in.?
China, manage general bureau's survey data according to national quality and show: the pesticide residue phenomenon in food largely exists in China, farming
Organophosphorus pesticide exceeding standard rate is 1%-35% in object.2010, Henan Province Kaifeng OPS pesticide residue recall rate was up to
14.5%, this long-term low dose contact organophosphorus pesticide seriously endangers human health.Just because of this, OPS residual becomes me
Pesticide residue security risk outstanding in daily life.It has now been found that in addition to traditional theory thinks organophosphorus pesticide
The activity that toxicity is able to suppress cholinesterase is outer, and the use of organophosphorus pesticide is by directly affecting the duplication of nerve cell and dividing
Change, serious damage directly is generated to intracerebral nervous system, by increasing the generation of active oxygen, so that lipid and protein generate
Oxidativestress damage directly damages cell DNA and leads to inflammatory reaction and the generation of nerve cell apoptosis, thus and cognitive function
Obstacle is related with the generation of neurodegenerative disease.Therefore, developing one kind can reduce nerve caused by long-term organophosphorus residue
The drug or functional product of toxicity are of great significance.
Astaxanthin (Astaxanthin, AST) also known as astaxanthin, astacin are a kind of fat-soluble keto-acid carotenoid,
Haematococcus pluvialis is to synthesize and accumulate the most microorganism of astaxanthin in nature, same in shrimp, crab, fish, yeast and plumage
Sample contains the ingredient of astaxanthin, as the nutrient for plants of microalgae, AST be in marine organisms body main carotenoid it
One.Astaxanthin has a variety of neuroprotective functions, including acute nerve injury and chronic nerve damage.The neuroprotection of astaxanthin
Effect mainly by it is anti-oxidant, anti-inflammatory possessed by it, inhibit the effect of apoptosis to play.Some researches show that astaxanthins to subtract
Shaohai Marko's Plastic Damage enhances hippocampus of adult rat nerve to occur and study note by increasing the area dentate fascia (DG) Hemodynamic environment
Recall especially Spatial memory ability, and have good improvement result to anxiety-depression, is prevention cognitive disorder disease
Effective native compound.Astaxanthin is the ocean that a kind of oxidation resistance is higher by ten times than other beta carotenes and lutein
The compound in source effectively can prevent the Neuro-degenerative disease as caused by neuron oxidative damage by blood-brain barrier
Disease.It is lost in addition, astaxanthin reduces hippocampal neuron by Anti-G value, this obtains the survival of newborn neuron effectively
Protection.
The drug of cognitive disorder caused by the poisoning for the treatment of chemicals and chronic nerve damage is mainly Edaravone at present
With the first-class drug of huperzine, and these drugs have the disadvantages of drug effect is not lasting enough, and side effect is larger mostly.Therefore, research and development are new
Type low toxicity is efficiently directed to chronic organophosphorus poisoning and the drug of cognitive disorder is caused to have important economic and social benefit.Both at home and abroad
Scholar is it has been reported that some preventing and treating the organic phosphorus drug for causing male reproduction toxicity and causing embryotoxicity of pesticide about astaxanthin
In application aspect patent (CN201410502878.5, CN201310018433.5), in addition, astaxanthin also be used to prepare
Treat anti-depression drug and preparation prevent and treat cerebral apoplexy drug in purposes (CN201210548264.1,
CN200810195924.6).Some scholars' report, lithium chloride answering in the cardiomyocyte apoptosis drug that anti-grease matter builds up induction
With (CN201510980704.4), the spirit such as the application (CN201610368414.9) in crystal methamphetamine cognitive disorder drug
The effect of stabilizer class treatment aspect, but it is chronic there is presently no being prevented and treated about astaxanthin joint lithium chloride in preparation
The research of cognitive disorder drug and application report caused by organophosphorus poisoning.
Summary of the invention
For the active drug not having also in the prior art for chronic organophosphorus poisoning cause cognition dysfunction, the present invention
Provide the drug that astaxanthin and/or lithium chloride prevent and treat cognitive disorder illness caused by chronic organophosphorus poisoning in preparation
In application.Astaxanthin joint lithium chloride treatment provided by the invention has mind to Hippocampal Injury caused by chronic organophosphorus poisoning
Through protective effect, and it can be improved by activation Akt/GSK3 β/CREB signal path and recognize function caused by chronic organophosphorus poisoning
It can obstacle.
For achieving the above object, the present invention, which adopts the following technical solutions, is achieved:
The present invention provides astaxanthins and/or lithium chloride to prevent and treat cognition caused by chronic organophosphorus poisoning in preparation
Application in the drug of disorder.
Further: the astaxanthin and lithium chloride are used in combination better than exclusive use astaxanthin or lithium chloride.
Further: the cognitive disorder illness includes spatial cognition obstacle, learning and memory dysfunction and spirit
Anxio-depressive disorders.
Further: the astaxanthin and/or lithium chloride can significantly improve the cognitive function of organophosphorus poisoning mouse, have
Help the recovery of mouse learning and memory ability.
Further: the astaxanthin and/or lithium chloride can significantly inhibit the sea of mouse caused by chronic organophosphorus poisoning
Horse tissue damage reduces apoptosis.
Further: the astaxanthin was with dosage gastric infusion 8 weeks of 50mg/kg/day；
Or the astaxanthin is with the dosage gastric infusion of 50mg/kg/day, and combines lithium chloride with 2mmol/kg/day
Dosage intraperitoneal injection is used in conjunction 8 weeks.
Further: the astaxanthin and/or lithium chloride can raise the activation levels of Akt/GSK3 β/CREB signal path,
Inhibit nerve cell apoptosis, improves cognition dysfunction.
Further: the astaxanthin combines lithium chloride with the dosage gastric infusion of 50mg/kg/day with 2mmol/
Kg/day dosage intraperitoneal injection is used in conjunction 8 weeks.
Further: described is organic phosphorus for Azodrin, phoxim, paraoxon and Hostathion.
Compared with prior art, the advantages and positive effects of the present invention are: it is research object that the present invention, which chooses astaxanthin,
It is disclosed in level in vivo and inhibits hippocampal neurons injury caused by chronic organophosphorus poisoning, improves the work of cognition dysfunction
With.
The present invention, which is verified by experiments astaxanthin joint lithium chloride treatment, has the function of significant anti-oxidant, inhibition apoptosis,
There can be neuroprotection to Hippocampal Injury caused by chronic organophosphorus poisoning, and can be by activating Akt/GSK3 β/CREB
Signal path improves cognition dysfunction caused by chronic organophosphorus poisoning, mitigates the anxiety-depression of mouse, shows this
Reagent has exploitation at the bright prospects of the drug of dementia caused by the chronic organophosphorus poisoning of novel prevention and treatment.
After a specific embodiment of the invention is read in conjunction with the figure, the other features and advantages of the invention will become more clear
Chu.
Detailed description of the invention
Fig. 1 shows organic phosphorus slow poisoning mouse brain hippocampus congo red staining result (400x, C in present invention test
Figure 200 x).In Fig. 1, A: control group；B and C model group；D: astaxanthin group；E and F: astaxanthin adds lithium chloride group；G and H: according to reaching
La Feng group；I lithium chloride group.
Fig. 2 shows organic phosphorus slow poisoning mouse brain Hippocampal CA 1 TUNEL coloration result in present invention test
(400x).In Fig. 2, A: control group；B: model group；C: astaxanthin group；D: Edaravone group；E: lithium chloride group；F: astaxanthin adds
Lithium chloride group.
Fig. 3 shows organic phosphorus slow poisoning mouse brain Hippocampal CA 1 p-PI3K ImmunohistochemistryResults Results in present invention test
(400x).In Fig. 3, A: control group；B: model group；C: astaxanthin group；D: Edaravone group；E: lithium chloride group；F: astaxanthin adds
Lithium chloride group.
Fig. 4 shows organic phosphorus slow poisoning mouse brain Hippocampus CA 3 Region p-GSK3 β ImmunohistochemistryResults Results in present invention test
(200x).In Fig. 4, A: control group；B: model group；C: astaxanthin group；D: Edaravone group；E: lithium chloride group；F: astaxanthin adds
Lithium chloride group.
Fig. 5 shows organic phosphorus slow poisoning mouse brain Hippocampus CA 3 Region p-CREB ImmunohistochemistryResults Results in present invention test
(200x).In Fig. 5, A: control group；B: model group；C: astaxanthin group；D: Edaravone group；E: lithium chloride group；F: astaxanthin adds
Lithium chloride group.
Specific embodiment
The technical scheme of the present invention will be explained in further detail with reference to the accompanying drawings and detailed description.
The present invention has rated astaxanthin joint lithium chloride treatment and leads to chronic organophosphorus poisoning according to internationally recognized method
The neuroprotection of the Hippocampal Injury of cause and the effect for improving cognition dysfunction.The astaxanthin that the present invention uses uses city
The product of face sale.
Embodiment 1, astaxanthin joint lithium chloride treat the influence to chronic organophosphorus poisoning cognitive disorder mice behavior
1) the lithium chloride treatment of Morris water maze laboratory evaluation astaxanthin joint influences exposed Mice behaviouristics
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.It is applied after contamination
Morris water maze tests the memory reproduction of mouse and spatial memory capacity.It totally 6 days, takes in control group mice 5 days and escapes
Keeping away preclinical mean value is reference value, while the difference for calculating 5 days average escape latencies of modeling mouse and reference value accounts for the mouse
The average escape latency time ratio, value > 20% then think model success, model success rate 90%.
After model is successfully prepared, astaxanthin group: astaxanthin gives stomach-filling with 50mg/kg/day dosage, and continuous 8 weeks；According to reaching
Edaravone is often only given 3mg/kg intraperitoneal injection, once a day, continuous 8 weeks by La Feng group；Lithium chloride group is by lithium chloride
(Licl) be often only given 2mmol/kg intraperitoneal injection, the next day it is primary, continuous 8 weeks.Astaxanthin inhibiting group by astaxanthin with
50mg/kg/day dosage gives stomach-filling, after by lithium chloride (Licl) be often only given 2mmol/kg intraperitoneal injection, the next day it is primary, even
It is 8 weeks continuous.
The results are shown in Table 1 for orientation navigation experiment, and in test in 5 days, model group mouse is found used in underwater hidden platform
Time is all remarkably higher than control group (P < 0.05), this shows model group mouse, and there are the damages of ability of learning and memory；Astaxanthin group
Time used in mouse escape latency is significantly shorter (P < 0.05) compared with model group；Edaravone group mouse escape latency
Also change with the time is gradually shortened, but no difference of science of statistics (the P > 0.05) compared with model group；Lithium chloride group mouse escapes latent
The volt phase is also obviously shortened (P < 0.05) compared with model group mouse；Astaxanthin adds lithium chloride group escape latency to have more compared with model group
Shorten significantly (P < 0.05), the mouse (P < 0.05) of remaining treatment group is shorter than the time required to the group.
The comparison result (x ± s, n=8) of each group mouse Morris water maze escape latency in 1 present invention of table
Compared with the control group:#P < 0.05；Compared with model group: * P < 0.05
Space exploration experimental result is as shown in table 2, takes the platform in pond after training by 5 days orientation navigations
Out, start to carry out each group mouse space exploration experiment test, record each group mouse is at target quadrant (quadrant where original platform)
The number of residence time ratio and spanning platform.Target quadrant residence time is longer and the number of spanning platform more
It is more, show that the mouse Spatial memory ability is better, it is on the contrary then poorer.Compared with the control group, model group mouse target quadrant
Residence time ratio shortens dramatically, and the number of spanning platform substantially reduces, this prompts chronic organic phosphorus cause cognitive disorder mouse
There is more serious damage (P < 0.05) in spatial memory capacity；Compared with model group, astaxanthin treatment group, Edaravone group,
Lithium chloride group and astaxanthin add the lithium chloride group mouse target quadrant residence time to increased, and spanning platform number also increases bright
Aobvious, especially astaxanthin adds lithium chloride group mouse test result the most significant (P < 0.05) compared with the variation of model group mouse, this shows
Astaxanthin combines the Spatial memory ability that lithium chloride inhibitor is caused cognitive disorder mouse to improvement by chronic organophosphorus poisoning
Significant effect.
The each group mouse target quadrant residence time is than the result (x ± s) with spanning platform number in 2 present invention of table
Compared with the control group:#P < 0.05；Compared with model group: * P < 0.05.
2) the lithium chloride treatment of elevated plus-maze test evaluation astaxanthin joint influences exposed Mice behaviouristics
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, exposed Mice behaviouristics is influenced using elevated plus-maze test evaluation drug.Mouse is placed in fan
Palace center (open arms and close arm junction), mouse head is towards open arms, and experimenter is apart from labyrinth center at least 1cm.Video recording system is opened,
The time that record experiment periods (5min) interior mouse enters open arms and closes the number of arm and be detained in two-arm respectively, when being stopped with open arms
Between percentage and enter opening and closing percentage of time reaction animal anxiety state.
Elevated plus-maze test result is as shown in table 3, model group mouse percentage of residence time, entrance at open arms
Open arms percentage of time is significantly lower than control group (equal p < 0.05), and model group mouse during the test frequency of occurrence compared with
The anxiety movement (such as rubbing pawl with the hands, scratch head etc.) of more mechanical sample repeatability, hints model is successfully established；Astaxanthin treatment group mouse
There is apparent growth (P < 0.05) compared with model group in open arms percentage of time, into open arms percentage of time；Edaravone group
Mouse is in open arms percentage of time compared with model group no difference of science of statistics (P > 0.05), into open arms percentage of time compared with model
Group is obviously shortened (P < 0.05), but effect does not have astaxanthin group obvious (P < 0.05)；Lithium chloride group mouse is in the open arms time
Percentage has apparent growth (P < 0.05) compared with model group in open arms percentage of time；Astaxanthin adds at lithium chloride group mouse
In open arms percentage of time, there is into open arms percentage of time the increase (P < 0.01) of very significant compared with model group, and is higher than
Other treatment group mouse.
In 3 present invention of table at each group mouse open arms the percentage of residence time and enter open arms percentage of time comparison knot
Fruit (x ± s)
Compared with the control group:#P < 0.05；Compared with model group:*P < 0.05**P < 0.01.
3) light and shade case experimental evaluation astaxanthin joint lithium chloride treatment influences exposed Mice behaviouristics
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, exposed Mice behaviouristics is influenced using the joint lithium chloride treatment of light and shade case experimental evaluation astaxanthin.
Light and shade case experimental results are as shown in table 4, model group mouse the camera-lucida region residence time percentage, wear case
The equal highly significant of frequency be lower than control group (P < 0.05, P < 0.05), and model group mouse frequency of occurrence during the test
The anxiety movement (such as rubbing pawl with the hands, scratch head etc.) of more mechanical sample repeatability；Compared with model group, astaxanthin treatment group, chlorination
Lithium group mouse the camera-lucida region residence time percentage, wear the frequency of case and exist and apparent increase (P < 0.05, P <
0.05), lithium chloride treatment group is better than astaxanthin group；Percentage comparison model of the Edaravone group mouse in the camera-lucida region residence time
Group mouse is not statistically significant (P > 0.05)；Astaxanthin add lithium chloride group mouse the camera-lucida region residence time percentage, wear
The frequency of case has the increase (P < 0.01, P < 0.01) of very significant compared with model group, and is higher than other treatment group mouse.
The percentage of each group mouse camera-lucida region residence time and the comparison result (x ± s) for wearing case frequency in 4 present invention of table
Compared with the control group: #p < 0.05；Compared with model group:*P < 0.05**P < 0.01.
To sum up, Morris water maze laboratory, elevated plus-maze test and light and shade case experiment the result shows that, astaxanthin connection
Closing lithium chloride treatment can significantly improve the cognitive function of organophosphorus poisoning mouse, facilitate the extensive of mouse learning and memory ability
It is multiple.
Embodiment 2, astaxanthin joint lithium chloride treatment are to chronic organophosphorus poisoning cognitive disorder Hippocampus of Mice form
Influence
1) congo red staining evaluation astaxanthin joint lithium chloride treats the influence to exposed Mice Hippocampal Injury
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, opens head and hippocampal tissue is taken to carry out paraffin section production, and application congo red staining evaluates astaxanthin
Joint lithium chloride treats the influence to exposed Mice Hippocampal Injury.
Congo red staining result is as shown in Figure 1, control group mice hippocampal slices have no Chinese red amyloid deposition, sea purslane
Shape returns back side cell band marshalling；In model group Hippocampus of Mice and the visible Chinese red amyloid of adjacent domain blood vessel endothelium
There is more apparent ribbon Chinese red precipitating in deposition, dentate fascia area, and hippocampal tissue pyramidal cell and have no that amyloid is heavy
Product, this prompts amyloid deposition damage caused by low dosage contact organophosphorus pesticide lighter, does not occur larger area patch also
Sample precipitating；Astaxanthin group, astaxanthin add blood vessel endothelium Chinese red amyloid deposition in lithium chloride group Hippocampus of Mice obviously to subtract
Gently, analysis is since astaxanthin can increase cerebral blood flow (CBF), this mitigates the amyloid deposition of blood vessel endothelium；Edaravone group with
Lithium chloride group simultaneously has no apparent improvement result.
2) TUNEL method evaluation astaxanthin joint lithium chloride treats the influence to exposed Mice apoptosis
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, opens head and hippocampal tissue is taken to carry out paraffin section production, and application TUNEL method evaluation astaxanthin connection
Close influence of the lithium chloride treatment to exposed Mice apoptosis.
TUNEL coloration result and compares as shown in Fig. 2, control group mice brain tissue Hippocampal CA 1 apoptotic cell is few or nothing
Group compares, and model group, astaxanthin group, Edaravone group, lithium chloride group, astaxanthin add the visible different degrees of apoptosis of lithium chloride group
Cell (P < 0.05)；Compared with model group, astaxanthin group, Edaravone group, astaxanthin add lithium chloride group Hippocampus of Mice to wither
It is more statistically significant (P < 0.05) to die cell, lithium chloride group compares no significant difference (P > 0.05)；Astaxanthin
There are statistical significance (P < 0.05) compared with Edaravone group for group；Astaxanthin group add lithium chloride group with astaxanthin compared with without system
Meter learns difference (P > 0.05), this shows that astaxanthin and Edaravone can reduce chronic organophosphorus poisoning and cause cognitive disorder mouse
The Apoptosis of hippocampus, astaxanthin therapeutic effect are better than Clinical Therapeutic Effects of Edaravone group, and lithium chloride recognizes chronic organophosphorus poisoning cause
Know that the improvement of obstacle hippocampus of mice area nerve cell apoptosis is unobvious.
In short, congo red staining and TUNEL decoration method are the result shows that astaxanthin joint lithium chloride treatment can significantly inhibit
The damage of Hippocampus of Mice caused by chronic organophosphorus poisoning, reduces apoptosis.
Embodiment 3, astaxanthin joint lithium chloride treatment to chronic organophosphorus poisoning cognitive disorder mouse Akt/GSK3 β/
The influence of CREB signal path activation levels
1) the lithium chloride treatment of Immunohistochemical Staining evaluation astaxanthin joint is to exposed Mice Akt/GSK3 β/CREB signal
The influence of signal pathway activated level
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, opens head and hippocampal tissue is taken to carry out paraffin section production, and application Immunohistochemical Staining evaluates shrimp
Green element joint lithium chloride treats the influence to exposed Mice Akt/GSK3 β/CREB signal path activation levels.
Immunohistochemical staining result is as shown in Figure 3-Figure 5, the p-PI3K of Fig. 3 it is immunohistochemical the result shows that, and it is right
Compare according to group, model group CA 1 Zone of Hippocampus in Mouse neuron obscure boundary and positive cell coloring is shallow, average optical density value is poor
Different statistically significant (p < 0.05)；Compared with model group, astaxanthin group, lithium chloride group, astaxanthin add lithium chloride group p-PI3K
Expression increase (P < 0.05), Edaravone group also has raising, but not statistically significant (the P > of difference compared with model group
0.05)。
The p-GSK3 β immunohistochemistry results of Fig. 4 show compared with the control group, p- in model group brain tissue hippocampus
GSK3 β positive staining is thin, and cell space is smaller, and positive cell substantially reduces, and average optical density value comparing difference is statistically significant
(P < 0.05)；Compared with model group, astaxanthin group, lithium chloride group, astaxanthin add the expression of lithium chloride group p-GSK3 β to increase
(P < 0.05), Edaravone group also has raising compared with model group, but difference is not statistically significant (P > 0.05).
The p-CREB immunohistochemistry results of Fig. 5 show that compared with the control group model group mouse positive cell significantly subtracts
Few, p-CREB expression is significantly inhibited (P < 0.05)；Compared with model group, astaxanthin group, Edaravone group, lithium chloride group,
Astaxanthin adds the expression of lithium chloride group p-CREB to increase (P < 0.05).
The expression of p-PI3K, p-Akt, p-GSK3 β and p-CREB relative to β-actin in 5 each group Hippocampus of Mice of table
Amount
Compared with the control group:#P < 0.05；Compared with model group:*P < 0.05.
2) the lithium chloride treatment of Western blot method evaluation astaxanthin joint is to exposed Mice Akt/GSK3 β/CREB signal
The influence of signal pathway activated level
Mouse establishes chronic organophosphorus poisoning animal model using subcutaneous injection contamination method.Contamination terminates and application is various
After drug-treated 8 weeks, supernatant is taken after taking hippocampal homogenates, evaluates the chlorination of astaxanthin joint using Western blot method
Lithium treats the influence to exposed Mice Akt/GSK3 β/CREB signal path activation levels.Western blot the result shows that, with
Control group is compared, and model group mouse p-PI3K, p-Akt, p-GSK3 β, p-CREB expression significantly reduce, and gray value analysis is poor
It is different that there is statistical significance (equal P < 0.05)；Compared with model group, astaxanthin group, lithium chloride group and astaxanthin add lithium chloride group
P-PI3K in Hippocampus of Mice, p-Akt, p-GSK3 β, p-CREB expression significantly improve, gray value analyzes difference tool
Statistically significant (P < 0.05), and astaxanthin group and astaxanthin add the expression water of lithium chloride group p-PI3K, p-Akt, p-CREB
It is flat to be higher than lithium chloride group mouse (P < 0.05)；The expression of Edaravone group is poor without statistics compared with model group gray value
Different (P > 0.05).
In short, immunohistochemistry and the prompt astaxanthin joint lithium chloride treatment of the result of western blot can raise Akt/
The activation levels of GSK3 β/CREB signal path improve cognition dysfunction to inhibit nerve cell apoptosis.
In conclusion the confirmation astaxanthin joint lithium chloride treatment of this experimental result has significant anti-oxidant, inhibition apoptosis
Effect, can to Hippocampal Injury caused by chronic organophosphorus poisoning have protective effect, and can by activation Akt/GSK3 β/
CREB signal path improves cognition dysfunction, mitigates the anxiety-depression of mouse, and display astaxanthin joint lithium chloride is controlled
Treating to have preferably resists chronic organophosphorus poisoning to cause cognitive disorder activity.
Astaxanthin source Yu Haiyang's shrimp crab shell of the invention or algae have resourceful, low in cost and safety
Many advantages, such as high, and prove that it has the work for preferably resisting chronic organophosphorus poisoning to cause cognitive disorder in level in vivo
Property, new approach is provided for the exploitation of such drug.
The above examples are only used to illustrate the technical scheme of the present invention, rather than is limited；Although referring to aforementioned reality
Applying example, invention is explained in detail, for those of ordinary skill in the art, still can be to aforementioned implementation
Technical solution documented by example is modified or equivalent replacement of some of the technical features；And these are modified or replace
It changes, the spirit and scope for claimed technical solution of the invention that it does not separate the essence of the corresponding technical solution.
Claims (5)
1. astaxanthin and lithium chloride are in the drug that preparation prevents and treats cognitive disorder illness caused by chronic organophosphorus poisoning
Application；The astaxanthin and lithium chloride can raise the activation levels of Akt/GSK3 β/CREB signal path, inhibit nerve cell
Apoptosis improves cognition dysfunction；The astaxanthin with the dosage gastric infusion of 50 mg/kg/day, and combine lithium chloride with
2mmol/kg/day dosage intraperitoneal injection is used in conjunction 8 weeks.
Recognize caused by chronic organophosphorus poisoning 2. astaxanthin according to claim 1 and lithium chloride are prevented and treated in preparation
Know the application in the drug of disorder, it is characterised in that: the cognitive disorder illness includes spatial cognition obstacle, study and note
Recall dysfunction and anxiety depressive disorder.
Recognize caused by chronic organophosphorus poisoning 3. astaxanthin according to claim 1 and lithium chloride are prevented and treated in preparation
Know the application in the drug of disorder, it is characterised in that: the astaxanthin and lithium chloride can significantly improve organophosphorus poisoning
The cognitive function of mouse facilitates the recovery of mouse learning and memory ability.
Recognize caused by chronic organophosphorus poisoning 4. astaxanthin according to claim 1 and lithium chloride are prevented and treated in preparation
Know the application in the drug of disorder, it is characterised in that: the astaxanthin and lithium chloride can significantly inhibit chronic organic phosphorus
The damage of Hippocampus of Mice caused by being poisoned, reduces apoptosis.
Recognize caused by chronic organophosphorus poisoning 5. astaxanthin according to claim 1 and lithium chloride are prevented and treated in preparation
Know the application in the drug of disorder, it is characterised in that: described is organic phosphorus for Azodrin, phoxim, paraoxon and triazole
Phosphorus.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104023722A (en) * | 2011-12-27 | 2014-09-03 | 杰拓保护有限公司 | Peritoneal dialysis fluid comprising a gsk-3 inhibitor |
| CN105078943A (en) * | 2014-05-04 | 2015-11-25 | 宁波大学 | Application of astaxanthin in preparation of products for prevention or treatment of preeclampsia |
| CN105106185A (en) * | 2015-09-25 | 2015-12-02 | 宁波大学 | Application of astaxanthin in preparation of medicine preventing and curing diabetic depression |
| CN105920034A (en) * | 2016-05-30 | 2016-09-07 | 宁波大学 | Application of lithium chloride to preparation of methamphetamine cognitive disorder medicament |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104023722A (en) * | 2011-12-27 | 2014-09-03 | 杰拓保护有限公司 | Peritoneal dialysis fluid comprising a gsk-3 inhibitor |
| CN105078943A (en) * | 2014-05-04 | 2015-11-25 | 宁波大学 | Application of astaxanthin in preparation of products for prevention or treatment of preeclampsia |
| CN105106185A (en) * | 2015-09-25 | 2015-12-02 | 宁波大学 | Application of astaxanthin in preparation of medicine preventing and curing diabetic depression |
| CN105920034A (en) * | 2016-05-30 | 2016-09-07 | 宁波大学 | Application of lithium chloride to preparation of methamphetamine cognitive disorder medicament |
Non-Patent Citations (1)
| Title |
|---|
| 氯化锂抑制β-淀粉样蛋白诱导细胞Tau蛋白磷酸化;孙治坤等;《中国药理学通报》;20080131;第24卷(第01期);24-28 * |
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