CN101376020B - Application of fungal immunomodulatory protein for inhibiting delta 5-desaturated enzyme - Google Patents
Application of fungal immunomodulatory protein for inhibiting delta 5-desaturated enzyme Download PDFInfo
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Abstract
The invention provides a novel application of a fungi immunomodulatory protein in inhibiting delta5-desaturase, through which chronic or acute inflammatory reactions, inflammation symptoms or inflammatory diseases induced by concentration disorder of delta5-desaturase, arachidonic acid or inflammatory eicosanoids can be prevented or treated. Particularly, the fungi immunomodulatory protein has better delta5-desaturase inhibitory effect together with gamma- linolenic acid. The fungi immunomodulatory protein is preferably Ganoderma lucidum immunomodulatory protein or Flammulina velutipes immunomodulatory protein.
Description
Technical field
The present invention relates to the new purposes of fungal immunomodulatory protein.
Background technology
Arachidonic acid (arachidonic acid, ARA) is the product of ω-6 polybasic unsaturated fatty acid metabolic process.Under natural situation, ARA seldom is present in the cell with free form, generally all is present on the phospholipid of cell membrane, particularly on the position of second carbon of lecithin, the pure and mild PHOSPHATIDYL ETHANOLAMINE of phosphatidyl-4.When cell is subjected to external irritant when activation (comprising physical property, chemical, physiological or other material), the phospholipid of cell membrane can be by activation and the effect of phospholipase, and with the hydrolysis of the ARA on the phospholipid and disengage free ARA.And free ARA is via the enzymatic reaction of Cycloxygenase (cyclooxygenases, COX) or xanthine oxidase (lipoxygenases, LOX), can form fast some lipid mediators that external information in the cell can be provided-be also referred to as class 20 acid.The metabolite of these ARA will affect the program of biological respinse, comprises inflammatory response.These products can form and act on the place of irriate or infection soon, and then with idiopathic decline or by enzyme and destroyed.
Described class 20 acid comprise prostaglandin and thromboxan.Prostaglandin and thromboxan can be divided into PGD, PGE, PGG, PGH or TXA, TXB according to its structure; Or can be divided into PGE1, PGE2 or PGE3 according to the double key number amount prostaglandin that it has, wherein with cause inflammation (pro-inflammaotry) relevant be PGE2, PGD2 and TXA2.Each kind 20 acid is all derivative by other special enzyme, and these enzymes are to be distributed in the specific tissue a bit, and for example TXA2 is produced by the platelet that contains thromboxane synthetase.PGD2 mainly is that mastocyte produces via the metabolism of Cycloxygenase path.Simultaneously, prostaglandin is relevant with hot morbidity phenomenon with pain in the inflammatory response, and wherein PGE2 is relevant with hyperpathia, and namely it can impel skin to have the allergic phenomena of height for pain, subsequently, histamine and slow-action element interacts with cytohormone and produces fever phenomenon.
Linolenic acid (linolenic acid, LA) is a kind of ω-6 polybasic unsaturated fatty acid, after the effect through Δ 6-desaturase, can change gamma-Linolenic acid (gamma-linolenic acid, GLA) into.GLA is linolenic first product of the mankind or animal metabolism, and the reaction rate of above-mentioned steps is quite slow, is the rate-determing step of polybasic unsaturated fatty acid metabolism.Under the effect of extending enzyme (elongase), most GLA can change dihomo-gamma-linolenic acid (dihomo-g-linolenic acid, DGLA) immediately into absolutely, then passes through the effect of Δ 5-desaturase, and part DGLA will form ARA.Another part DGLA then passes through the effect of COX, forms the class 20 sour PGE1 of anti-inflammatory, and the PGE1 of formation can significantly suppress the formation of inflammatory class 20 sour PGE2.In the metabolic process of ω-6 polybasic unsaturated fatty acid, Δ 6-desaturase and Δ 5-desaturase are two enzymes, particularly Δ 5-desaturase that determine reaction rate, and it has determined the formation of ARA in the body.
GLA is mainly from the seed of several special plants, for example contains 23% borage seed oil (BorageOil), 18% black gooseberry seed oil (Blackcurrant Seed Oil) and 9% Radix Oenotherae erythrosepalae seed oil (Evening Primose oil).Then be few appearance in animal body.Many experimental results all confirm the effect that GLA has anti-inflammatory and regulates immunocompetence.Δ 6-desaturase very easily is subject to the impact of age, the interior hormone of body and morbid state and lowers activity, and correspondingly, GLA content is also lower in its body.In vivo, the activity of Δ 6-desaturase also can comprise arthritis along with various diseases, diabetes, hypertension, eczema and psoriasis and descend.In addition, life pattern factor such as pressure, smoking, drinks, linolenic acid and Related product saturated and that trans fatty acid is too high, and the shortage of vitamin B6, zinc and magnesium etc. all can suppress the activity of Δ 6-desaturase.Above-mentioned reason all can reduce the generation in vivo of GLA, the minimizing of GLA content relatively also reduces DGLA content in vivo, and the situation disequilibrium that further causes DGLA and ARA jointly to compete Cycloxygenase/xanthine oxidase, so that ARA produces the inflammatory prostaglandin in a large number.
In recent years, there are many research institutions to attempt finding out the active substance that suppresses Δ 5-desaturase.But the neither ideal of effect, and existing anti-inflammatory drug easily develops immunity to drugs in patient body, therefore poor effect.Therefore, be necessary to provide a kind of novel anti-inflammatory medicine to satisfy inflammation patient's demand.
Summary of the invention
The object of the present invention is to provide the application of fungal immunomodulatory protein (fungi immunodulatory protein, FIP) in suppressing Δ 5-desaturase.
Described fungal immunomodulatory protein is preferably Ganoderma lucidum immunoregulation protein or gold needle mushroom immunomodulatory protein.
Wherein this inhibition Δ 5-desaturase activity is for prevention or treats the reaction of chronic or acute inflammation, inflammation symptom or the inflammatory disease of being lacked of proper care and being caused by the concentration of Δ 5-desaturase, arachidonic acid or 20 acid of inflammatory class.Described inflammatory disease is asthma, arteriosclerosis, obesity, diabetes, gastroenteropathy, cardiovascular disease, arthritis, osteoporosis, periodontal disease, cancer, autoimmune disease, allergy, rheumatoid arthritis, menstrual pain or gout.
In yet another embodiment of the present invention, when suppressing Δ 5-desaturase, also use gamma-Linolenic acid.Described gamma-Linolenic acid comes from the extract of plant or microbial food.
Prevention of the present invention or treatment inflammatory response are the addition effect of the mechanism of action of following two kinds of compositions:
(a) suppress the effect of Δ 5-desaturase by fungal immunomodulatory protein, and reduce arachidonic concentration, and then reduce the concentration of inflammatory class 20 acid, and
(b) gamma-Linolenic acid can change dihomo-gamma-linolenic acid into and increase its concentration, forms in a large number the concentration of anti-inflammatory class 20 acid.
In other embodiments of the present invention, when suppressing Δ 5-desaturase, also using dihomo-gamma-linolenic acid.
By suppressing the activity of Δ 5-desaturase, can reduce the growing amount of ARA, thereby reduce the amount that is changed class 20 acid that form by ARA; Perhaps, increase the concentration of DGLA, and the content of Δ 5-desaturase is constant, then the DGLA in the body can't change ARA in a large number into, and then makes the concentration of DGLA be higher than ARA.The present invention is by the regulation and control to the metabolism of ω-6 polybasic unsaturated fatty acid, and a kind of novel anti-inflammatory medicine is provided, and helps the patient to alleviate uncomfortable symptom.
Ganoderma lucidum immunoregulation protein was separated called after LZ-8 (Ling Zhi-8) in 1989 by people such as Japanese scholars Kino in the G.lucidum mycelium.LZ-8 is comprised of 110 aminoacid, and molecular weight is 12,420Da, and with the aminoacid sequence of the Variable Area in heavy chain immunoglobulin district and secondary structure to a certain degree similarity is arranged.LZ-8 ortho states (native form) is that the form with homodimer exists, and has to promote lymph corpuscle propagation and the effect that suppresses systemic anaphylaxis (systemic anaphylaxis reaction) and local anaphylaxis (Arthus reaction).In addition, LZ-8 can produce agglutination for the sheep erythrocyte, and any agglutination is not but occured human erythrocyte, and this shows that LZ-8 has the potentiality of its application at human medical.
" suppressing Δ 5-desaturase active " of the present invention, can be used for inflammatory response, symptom and disease that prevention or treatment are lacked of proper care and caused by the concentration of Δ 5-desaturase, ARA or 20 acid of inflammatory (pro-inflammatory) class.The better instantiation of this type of disease includes but not limited to, asthma (J of the American DieteticAssociation, January 2005,98-106), arteriosclerosis (Prostaglandins, Leukotrienes andEssential Fatty Acids 76 (2007) 251-268), fat (Nutrition, 2001; 17,953-966), diabetes (J Lipid Res.2006 Sep; 47 (9): 2028-41.; Prostaglandins Leukot Essent Fatty Acids.2003 Feb; 68 (2): 151-62; ), gastroenteropathy, ulcerative colitis (Clin.Sci., 1987,73,361-364), Crohn disease (Clin.Sci., 1987,73,361-364), cardiovascular disease, arthritis (JointBone Spine.2005 Dec; 533-9.Epub 2004 Dec 15), osteoporosis (Clin.Nutr., 2000,19 72 (6):, 271-276), periodontal disease (Clin.Nutr., 2000,19,271-276), cancer (Recent ResultsCancer Res.2007; 174:37-47.; Toxicology.2000 Nov 16; 153 (1-3): 11-26.) and autoimmune disease (Lipids.2003 Apr; 38 (4): 323-41.; Proc Nutr Soc.1998 Nov; 57 (4): 555-62.), irritated (Curr Drug Targets Inflamm Allergy.2005 Apr; 4 (2): 151-5.), rheumatoid arthritis (Rheumatol Int.2003 Jan; 27-36.Epub 2002 Sep 6.), menstrual pain or gout (ArthritisRheum.2000 Aug 23 (1):; 43 (8): 1779-89.; Inflammation.1997 Apr; 21 (2): 205-22) etc. (Equine Vet is May J.1984 for chronic or acute inflammation disease; 16 (3): 163-75).
" fungal immunomodulatory protein " of the present invention includes but not limited to, Ganoderma lucidum immunoregulation protein (LZ-8, FIP-gts) or gold needle mushroom immunomodulatory protein (FIP-fve).
" anti-inflammatory " of the present invention is the effect by inhibition Δ 5-desaturase, and reduces arachidonic concentration, and then reduces the concentration of inflammatory class 20 acid.
Can comprise gamma-Linolenic acid in the medicine of the present invention, it is used for prevention or treats inflammatory response, symptom and the disease of being lacked of proper care and being caused by the concentration of Δ 5-desaturase, arachidonic acid or 20 acid of inflammatory class.This disease preferred embodiments includes but not limited to pant, the inflammatory disease of arteriosclerosis, obesity, diabetes, gastroenteropathy, cardiovascular disease, arthritis, osteoporosis, periodontal disease, cancer, autoimmune disease, allergy, rheumatoid arthritis, menstrual pain or gout.In detail, prevention or treatment inflammatory response are the addition effect of the mechanism of action of following two kinds of compositions: (a) suppress the effect of Δ 5-desaturase by fungal immunomodulatory protein, and reduce arachidonic concentration, and then the concentration of reduction inflammatory class 20 acid, reaching (b), GLA can change DGLA into and increase its concentration, a large amount of concentration that form 20 acid of anti-inflammatory class suppress the formation of inflammatory class 20 acid.
GLA among the present invention can come from the extract of plant or microbial food, is commercially available or is prepared from by the method that those of ordinary skills know.
Description of drawings
Fig. 1 is the metabolic map of ω-6 polybasic unsaturated fatty acid;
Fig. 2 is the cytotoxicity MTT analysis result of rFIP;
Fig. 3 is the cytotoxicity MTT analysis result of GLA;
Fig. 4 is DGLA when being 100M, and rFIp is on the impact of Δ 5-desaturation, DGLA and the ARA of RAW 264.7 macrophages;
Fig. 5 is DGLA when being 25M, and rFIP is on the impact of Δ 5-desaturation, DGLA and the ARA of RAW 264.7 macrophages;
Fig. 6 is that the GLA of variable concentrations and rFIP are on the impact of Δ 5-desaturation, DGLA and the ARA of RAW 264.7 macrophages.
The specific embodiment
The invention provides the new application of fungal immunomodulatory protein (fungi immunodulatory protein, FIP) in Δ 5-desaturase.Described fungal immunomodulatory protein is Ganoderma lucidum immunoregulation protein or gold needle mushroom immunomodulatory protein.Also can comprise gamma-Linolenic acid in the application of the present invention.
One, experiment material and test
Preparation and the active testing of (1.1.rFIP recombinant fungus immune protein)
Utilize yeast (Saccharomyces cerevisiae) expression vector system to express rFIP.According to the yeast nutritional need filter out with expression vector turn shape bakery yeast bacterial strain, confirm to filter out yeast with rFIP via Western blot mode.The purity of test protein and rFIP are active.The rFIP concentrated solution of purification is stored in-20 ℃ for the experiment use.
1.2.RAW the cultivation of 264.7 macrophages
RAW 264.7 cells are mouse macrophage, are caused with Abelson murine leukemia degree by BALB/c mouse, available from Foodstuff Industrial and Development Inst..Be incubated in 37 ℃, the incubator of 5%CO2 with the DMEM culture fluid that contains 10%FBS.When treating that Growth of Cells to 80%～90% converges, remove culture fluid and add simultaneously a small amount of culture fluid, utilize burning-in knife that cell is scraped cell totally from the 75T flask, and put into centrifuge tube, add again culture fluid after centrifugal cell concentration is adjusted into 1x106 cell/ml, plant 96 hole tissue cultures dish or 10-cm Tissue Culture Dish, be incubated at 37 ℃ of incubators that contain 5%CO2, after cell attached 4 hours, the rFIP or the GLA that add variable concentrations reacted 24 hours again.
Two, experimental drug
Chloroform;
3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl Thiazolyl blue tetrazolium bromide compound; Thiazolyl blue)
(MTT，Sigma，M-2128，USA)
DMEM culture medium, Dimathyl sulfoxide (DMSO)
Ethanol, hyclone (FBS), isopropyl alcohol (J.T.Baker, USA)
Lipopolysaccharide (LPS, Sigma, L-2755 Escherichia coli (E.Coli) Serotype USA)
Phosphate buffer (D-PBS, GIBCO BRL, USA)
Platform is expected orchid (Sigma, USA)
Three, instrument and equipment
The carbon dioxide constant incubator
Aseptic convulsion cabinet
Thermostatic type water temperature groove
Blood cell calculator
Inverted phase contrast microscope
Enzyme Linked Immunoadsorbent Assay instrument (ELISA)
Acid-base meter
The GC analyser
Four, lipid extraction
Be 1x10 with cell concentration at first
6RAW 264.7 cells of cell/mL are implanted in 10mL/10 cm culture plate, 37 ℃ cultivate 4 hours after, add the rFIP of variable concentrations or/and GLA reaction after 24 hours, after utilizing PBS to clean 2 times, add the PBS of 3mL, then utilize burning-in knife that RAW 264.7 cells on the culture plate are scraped, and put into the teat glass of the 8mL tool screw lid that has indicated, glass tubing is put into centrifuge, PBS was removed in centrifugal 5 minutes with 1000rpm, at last the glass serpentine pipe is put into-20 ℃ of refrigerator freezings.
Glass serpentine pipe testing sample is after room temperature is thawed, extract immediately TL in the cell: add the 0.5mL deionized water in the glass serpentine pipe and make cell rupture, the chloroform/methanol mixed liquor of adding 20ml (2: 1, v/v), at least left standstill 1 hour or place refrigerator overnight, with the extraction TL.After the extraction, add the 0.9%NaCl solution that accounts for cumulative volume 20%, to separate chloroform and water layer.Testing sample is in 4 ℃, and 1000rpm after centrifugal 5 minutes, minutes two layers up and down, will include in the glass tubing of chloroform layer dislocation 10mL Telfon-nut of TL.Place under the constant speed nitrogen current, allow chloroform evaporated to doing in 40 ℃.The lipid that again residue is dried up dissolves again with the 0.5mL chloroform.Add 2mL boron trifluoride methanol solution, vortex (vortex), lid screws, in 90 ℃ of heating 15min.After the cooling, add an amount of hexane, after evenly mixing, the fatty acid that will methylate again extracts, and can directly be GC and analyze.
Five, analytical conditions for gas chromatography (GC analysis)
Get the sample (standard substance, testing sample) after the above-mentioned processing of 2 μ L, utilize automatization's gas chromatograph: desktop HP 6890 (Hewlett Packard, PA, USA) be furnished with the composition that flame ion detector (Flameionization detector) is analyzed fatty acid.Employed gas chromatography tubing string is selected Omegawax 320
TMOther condition of capillary column (30.0m * 320 μ m ID * 0.25 μ m film) is set as follows:
Carrier gas: set H
2Flow velocity is 32mL/min; The setting air flow velocity is 350mL/min.
Entrance is made as schizotype; Heater: 205 ℃; Pressure: 20psi; Overall flow rate: 14.7mL/min
Set baking temperature: initial temperature: 140 ℃, zero-time: 1 minute,
Temperature rate-of-rise: 12 ℃/minute, 205 ℃ of final temperatures were kept 20 minutes.
50 ℃/minute, 245 ℃ of final temperatures were kept 5 minutes
Set the inlet temperature: 205 ℃
Set detector temperature: 235 ℃
Six, the dosage of assessment rFIP or GLA is on the impact of macrophage survival rate
RAW 264.7 macrophages are with 1x10
6The concentration of cell/mL is inserted 96 well culture plates, the GLA that adds rFIP and 500,200,100,50,25, the 10 μ M of variable concentrations 100,40,20,10,5,2.5,1.25,0.625,0.3125 μ g/mL cultivated after 24 hours, throw aside culture fluid, remaining cells carries out MTT and analyzes.MTT analyzes the method with reference to the people such as Mosmann (1983), MTT is former to be yellow water soluble compound, can be reduced into purple crystal by dehydrogenase, and when cytoactive when high or number is many, then dehydrogenase activity is also higher in the cell, and the crystallization that then has more purples in the cell forms.With 10 times of MTT storage liquid dilutions, will through rFIP or/and the cell that GLA processes adds 55 μ l/ hole MTT solution, subsequently it be put 37 ℃, 5%CO with DMEM
2Incubator in cultivated 2 hours, remove supernatant, the 0.04 N HCl/ isopropyl alcohol that adds again 100 μ l/ holes with the 150rpm concussion with the toner stripping, and under room temperature lucifuge 1 hour, read at last the light absorption value of 540nm with ELISA.Agent prescription: 1) MTT solution: be configured to the 5mg/mLMTT storage liquid with PBS, filter with 0.2 μ m filter membrane again, and lucifuge stores; 2) acid-isopropyl alcohol: 0.06N HCl is dissolved in isopropyl alcohol.
Seven, the dosage of I. assessment rFIP and GLA is on the impact of macrophage survival rate
Must determine at first whether rFIP can suppress or kill the RAW264.7 macrophage.The rFIP of variable concentrations added in the culture medium cultivated 24 hours, when learning the concentration of rFIP≤10 μ g/mL by the MTT analysis result without significant cytotoxicity (Fig. 2).The GLA of variable concentrations (10-500 μ M) adds RAW 264.7 macrophages and cultivated 24 hours, observes its GLA to the toxicity of macrophage.There is no significant cytotoxicity (Fig. 3) when in the MTT analysis result, learning the concentration of GLA≤100 μ M.
II. utilize the fatty acid analysis method to assess rFIP or rFIP+GLA to the impact of the desaturation of the Δ 5-desaturase of RAW 264.7 macrophages
1.rFIP the impact on RAW 264.7 macrophage fatty acids composition
Be 1x10 with concentration
6The macrophage kind of cell/ml enters to contain in tissue culture's ware of culture fluid, is incubated at 37 ℃ and contains 5%CO
2Incubator, after cell attaches 4 hours, add again the rFIP of 10g/mL, cultivate after 24 hours, extract the fatty acid of cell and analyze with above-mentioned the 4th step.The result is as shown in table 1, and rFIP does not cause significant impact for the fatty acid composition of macrophage.
Table 1 rFIP is for the impact of the fatty acid composition of macrophage
| Contrast | rFIP | |
| MEAN±SD | MEAN±SD | |
| C14:0 C14:1n-5 C15:0 C16:0 C16:1n-7 C18:0 C18:1 C18:2n-6 C18:3n-6 C20:0 C20:1n-9 C20:2n-6 C20:3n-6 C20:4n-6 C20:5n-3 C22:2n-6 C22:4n-6 C22:5n-3 C22:6n-3 | 3.23±0.15 0.57±0.04 0.20±0.28 20.60±1.30 11.73±0.05 5.34±7.56 39.96±4.09 1.64±0.03 0.00±0.00 0.00±0.00 1.30±0.42 2.63±0.32 0.85±0.05 6.45±0.14 0.59±0.01 0.27±0.38 0.33±0.47 1.85±0.19 2.47±0.11 | 2.62±0.74 0.45±0.39 0.27±0.24 20.43±0.62 12.14±0.28 11.78±0.34 34.76±0.41 1.65±0.01 0.00±0.00 0.28±0.24 0.51±0.02 2.17±0.08 0.91±0.04 6.66±0.15 0.63±0.03 0.16±0.28 0.22±0.38 1.89±0.09 2.47±0.10 |
Because Δ 5-desaturation is to change DGLA into ARA, we are fixed as 25 μ M and 100 μ M with the concentration of DGLA, with variable concentrations (2.5,5,10,20 μ g/mL) rFIP adds in the culture fluid of cell, cultivates 24 hours, extracts the fatty acid of cell with above-mentioned the 4th step again and analyzes.
2. the rFIP of variable concentrations is on (the impact of DGLA → ARA), DGLA and ARA of the Δ 5-desaturation of RAW 264.7 macrophages
Can clearly find out from Fig. 4, the composition of cell fatty acid is at the DGLA that has added 100M and variable concentrations (2.5,5,10﹠amp; After rFIP 20g/ml) cultivated, the amount of ARA reduced gradually; Relatively, the amount of DGLA then increases.If calculate and compare simultaneously the conversion ratio of Δ 5-desaturation
*, can see that conversion ratio is down to 17.4% by 26.2%.
*The formula of conversion ratio { [ARA]/([ARA]+[DGLA]) } * 100%
The content of Fig. 5 and Fig. 4 is similar, just the concentration of the DGLA of 100M is reduced to 25M.Observe and whether can obtain similar result.From found that, very similar to the experimental result of Fig. 4: the amount of ARA reduces gradually; The amount of DGLA then rises.The conversion ratio of Δ 5-desaturation also is down to 48.3% from 66.8%.
Can find that from Fig. 4 and Fig. 5 rFIP can suppress Δ 5-desaturation (DGLA → ARA), and the ability that suppresses increases along with the increase of rFIP concentration; RFIP also can affect the content of the interior DGLA of cell and ARA simultaneously.
3. the GLA of variable concentrations and rFIP are on (the impact of DGLA → ARA), DGLA and ARA of the Δ 5-desaturation of RAW 264.7 macrophages
Owing to GLA can change DGLA into via the extension enzyme effect of macrophage, so this experiment needn't add DGLA again.Fixedly the concentration of rFIP is 10 μ g/mL, then adds respectively the GLA (12.5,25,50,100 μ M) of variable concentrations, cultivates after 24 hours, with the fatty acid of above-mentioned the 4th step extraction cell and analyze.
Result by Fig. 6 can find out, Growth of Cells only contains a small amount of n-6 PUFA in general culture medium, so the DGLA that Growth of Cells produces in culture medium and ARA are with regard to (0 μ M) on the low side; But after GLA begins to add (12.5 μ M), the amount of DGLA and ARA just begins to rise.After GLA concentration constantly rose, because rFIP can suppress Δ 5-desaturation, the amount of ARA just no longer rose, and begins on the contrary descend (50 μ M); And the amount of DGLA continues to increase.By the time during 100 μ M, the amount of ARA continues toward descending, but DGLA still rises.Make the amount gap of two kinds of fatty acids become large.In addition, the prescription of rFIP+GLA is also so that the conversion ratio of Δ 5-desaturation is down to 30.4% from 88.0%.So rFIP+GLA can increase the content of DGLA in the body, suppress the content of ARA, and inhibition Δ 5-desaturation (DGLA → ARA).
*The formula of conversion ratio { [ARA]/([ARA]+[DGLA]) } * 100%
Fungal immunomodulatory protein of the present invention can be made into the yeast with intact cell, can be directly use and can bring into play biological activity in organism with oral way, step that need not any purification, thus reduce cost on producing.
The invention provides the fungal immunomodulatory protein of relevant purification or contain the route of administration of fungal immunomodulatory protein host cell.The mode of taking can be with intravenous injection, lumbar injection, intramuscular injection, oral, the per mucous membrane layer absorbs, contact skin absorbs or to be soaked in form or other the applicable drug delivery path in the liquid.And wherein in the oral application mode for paying the utmost attention to method.
The fungal immunomodulatory protein of purification provided by the invention or contain the fungal immunomodulatory protein host cell and can be widely used in mammals, Fish, shell-fish and livestock products, poultry.Here the mammals of indication and poultry are pig, chicken.The indication Fish are cabrilla, salmon, Squaliobarbus ourriculus.The indication shell-fish is shrimp, Lobster, grass shrimp, speckle joint shrimp, white shrimp.The present invention is applied in fresh water or sea water animal, during such as Fish, also may be dipped in the liquid that contains Ganoderma lucidum immunoregulation protein, is adsorbed onto in the fish body by the gill.
The invention provides and orally comprise the application of fungal immunomodulatory protein compositions of the present invention and reach immunoregulatory function.This Ganoderma lucidum immunoregulation protein can be from Ganoderma prepare or from escherichia coli (E.coli) or fungus for example bread microzyme (Saccharomyces cerevisiae) prepare.
Claims (4)
1. the application of Ganoderma lucidum immunoregulation protein in preparation Δ 5-desaturase inhibitors.
2. application as claimed in claim 1, wherein said Δ 5-desaturase inhibitors suppress Δ 5-desaturase, and reduce arachidonic concentration.
3. application as claimed in claim 1 further comprises the application gamma-Linolenic acid.
4. application as claimed in claim 3, wherein said gamma-Linolenic acid comes from the extract of plant or microbial food.
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| CN102949707A (en) * | 2011-08-23 | 2013-03-06 | 柯俊良 | Treatment on inflammation caused by respiratory syncytial virus by developing flammulina velutipes immune adjustment proteins and lucid ganoderma immune adjustment proteins and reduction of virus dosage |
| CN103463618B (en) * | 2013-09-06 | 2014-09-03 | 张喜田 | Application of recombinant ganoderma lucidum immunoregulatory protein in preparing drug for treating focal cerebral ischemia |
| CN103751765B (en) * | 2014-02-12 | 2015-02-25 | 张喜田 | Application of recombined ganoderma lucidum immunoregulation protein (rLZ-8) to preparation of medicine for treating tissue fibrosis |
| CN104069481B (en) * | 2014-07-29 | 2015-11-11 | 张喜田 | The application of recombinant Ganoderma lucidum immunoregulation protein (rLZ-8) lipoprotein content in adjusting blood lipid |
| TWI726904B (en) * | 2015-09-03 | 2021-05-11 | 益生生技開發股份有限公司 | Medical uses of fungal immunomodulatory proteins in treatment and prophylaxis of alveolar bone loss due to periodontal disease |
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