CN109771404A - Application of butyric acid in the preparation of drugs for preventing and/or treating autoimmune diseases - Google Patents
Application of butyric acid in the preparation of drugs for preventing and/or treating autoimmune diseases Download PDFInfo
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Abstract
本发明提供了丁酸在制备预防和/或治疗自身免疫性疾病药物中的应用，属于自身免疫性疾病治疗技术领域，根据本发明实施例的记载，丁酸预防性干预可显著抑制实验性关节炎的发生发展，使关节炎发病率下降74％，并保护关节滑膜组织免受炎性细胞浸润和侵蚀破坏。丁酸可增加抗炎因子IL‑10的表达，同时减少自身抗体anti‑CII以及促炎因子IL‑6的产生。进一步，丁酸促进关节淋巴结以及肠道派氏结(peyer's patches，PP)Treg细胞分化，并抑制Tfh细胞表达；丁酸还可以下调肠道派氏结生发中心B(germinal center B，GCB)细胞。
The invention provides the application of butyric acid in the preparation of medicines for preventing and/or treating autoimmune diseases, belonging to the technical field of treatment of autoimmune diseases. According to the records of the embodiments of the present invention, the preventive intervention of butyric acid can significantly inhibit experimental joints The occurrence and development of inflammation reduces the incidence of arthritis by 74%, and protects the synovial tissue from inflammatory cell infiltration and erosion. Butyrate can increase the expression of anti-inflammatory factor IL-10, while reducing the production of autoantibody anti-CII and pro-inflammatory factor IL-6. Furthermore, butyric acid promotes the differentiation of articular lymph nodes and intestinal Peyer's patches (PP) Treg cells, and inhibits the expression of Tfh cells; butyric acid can also downregulate intestinal Peyer's node germinal center B (GCB) cells .
Description
Technical field
The invention belongs to treatment of autoimmune diseases technical fields more particularly to butyric acid in preparation prevention and/or treatment
Application in autoimmune disease drug.
Background technique
Autoimmune disease, such as systemic loupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjogren syndrome (SS)
It is using immune inflammation as the diffusivity connective tissue or diseases associated with inflammation of outstanding behaviours disease.Occur in serum it is a variety of it is pathogenic from
Body antibody and multisystem involvement are the main clinical characteristics of such disease.For example, SLE morbidity's initial stage more show as low-heat,
The clinical symptoms such as facial rash, out of strength, alopecia, arthralgia, serious person will appear the neurological symptoms such as twitch, syncope, advanced stage
Multiple exhibition is chronic nephritis even kidney failure.Illness rate of the disease in China is about 70/,100,000 people, i.e. number of patients is up to 90
Ten thousand or so, and 5 years survival rates only have 50~85%, poor prognosis seriously threatens the quality of life of patient, to patient and social band
Heavy spirit and financial burden are come.Rheumatoid arthritis is a kind of system characterized by multi-joint erosive synovia inflammation
Property autoimmunity disease, illness rate 0.28-0.41%, there are about 5,000,000 patients in China, and mostly young and middle-aged women, without regular
Disability rate is treated up to 75%.In the Second China National Sample Survey on Disability that China was carried out in 2006, crippling arthropathy exists
Cause to arrange the 2nd (20.1%) in the 21 class causes of disease of physical disabilities, cerebrovascular disease (20.6%) is only second to, wherein 79.4% is
RA is disabled.
Autoimmune disease is the systemic autoimmune diseases that a kind of driving of antigen, T cell mediate.Its initiating fallen ill
Link first is that the abnormal activation and its immune imbalance of T lymphocyte, it is multinomial that researches show that Treg is the tune for maintaining immunologic balance
Section property cell, in the inflammatory reaction and antibody generation process that infection or autoantigen induce, in periphery inducing immune tolerance.
Currently, the treatment method of autoimmunity disease and its immune-related inflammatory disease be still hormone, immunosuppressor and
Biological agent, excessive immunosupress, which can not reach effective remission and would generally bring patient, brings infection etc. no
Good reaction.Therefore find it is a kind of can reverse immune imbalance, rebuild immune tolerance, the treatment method for adjusting immunologic balance seems especially
It is important.
Summary of the invention
In view of this, the purpose of the present invention is to provide butyric acid in preparation prevention and/or treatment autoimmune disease medicine
Application in object.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical schemes:
Application of the butyric acid in preparation prevention and/or treatment autoimmune disease drug.
It preferably, further include that butyric acid pharmaceutically receives in the drug of the prevention and/or treatment autoimmune disease
Auxiliary material.
Preferably, the butyric acid prevent and/or treat autoimmune disease drug in mass content be 10~
90%.
The present invention provides application of the butyric acid in the drug that preparation inhibits the expression of autoantibody and proinflammatory factor.
Preferably, the proinflammatory factor includes the IL-6 factor.
The present invention provides application of the butyric acid in the drug that preparation promotes the expression of anti-inflammatory factors, the anti-inflammatory factors packets
Include the IL-10 factor.
The present invention provides butyric acid answering in the drug that preparation promotes joint lymph node regulatory T cells Treg differentiation
With.
The present invention provides application of the butyric acid in the drug that preparation inhibits folliculus helper T lymphocyte Tfh expression.
The present invention provides application of the butyric acid in the drug that preparation inhibits Germinal center B cell GCB expression.
Butyric acid adjusts the application in serum short chain fatty acids drug in preparation.
Beneficial effects of the present invention:
The present invention provides application of the butyric acid in preparation prevention and/or treatment autoimmune disease drug, butyric acid is controlled
The animal model for treating rheumatoid arthritis RA can effectively reduce destruction of joint, correct for the intracorporal unbalance shape of immunocyte of biology
State.Record according to an embodiment of the present invention, butyric acid Primary preventive intervention can significantly inhibit the occurrence and development of experimental arthritis, make to close
Scorching disease incidence decline 90% is saved, and Saving cortilage synovial tissue is from inflammatory cell infiltration and erosion damage.Butyric acid can increase anti-
The expression of scorching factor IL-10, while reducing the generation of autoantibody anti-CII and proinflammatory factor IL-6.Further, butyric acid
Promote joint lymph node and intestinal tract Peyer's patch (peyer's patches, PP) Treg cell differentiation, and inhibits Tfh cell table
It reaches.The ratio of intestinal tract Peyer's patch centrum germinativum B (germinal center B, GCB) cell is also obviously lowered.Meanwhile butyric acid is also
The species diversity that intestinal flora can be increased is enriched with Treg cell correlation probiotics.In addition, butyric acid is to experimental arthritis
It with therapeutic effect, can significantly alleviate arthritic symptom, increase the synthesis of the IL-10 factor and the IL-6 factor and autoantibody life
At reduction.
The application of butyric acid of the present invention, provides the new method for the treatment of of autoimmune diseases, and the adjusting of targeting is different
Normal T cell treats disease from upstream pathway, adjusts immunologic balance.
Detailed description of the invention
Fig. 1 is that gas chromatography-mass spectrometry (GC-MS) detects rheumatoid arthritis patients (RA, n=30) and health
Control crowd (HC, n=24) excrement Short-Chain Fatty Acids content balance result；
Fig. 2 is butyric acid feed in embodiment to the disease incidence (A) of experimental arthritis and the influence of arthritis score (B)；
Fig. 3 is the joint CT imaging after butyric acid is intervened, and upper row is soft tissue of joint imaging, and lower row is that joint bone tissue is in
Picture, wherein Con:control, Normal group；CIA: disease group；CIA+But: butyric acid intervention group；
Fig. 4 is influence of the butyric acid intervention to synovial tissue of joint's cell infiltration and osteoclasia, and pathological score is expressed as
Mean ± SD, every group of P < 0.01 mouse n=8, * *；CIA: disease group；CIA+But: butyric acid intervention group；
Fig. 5 is butyric acid intervention to autoantibody anti-CII (A), proinflammatory factor IL-6 (C) and anti-inflammatory factors IL-10 (B)
The influence of expression；
Fig. 6 is the influence that joint lymph node Treg cell differentiation and Tfh cell are expressed in butyric acid intervention, wherein left side is stream
Formula result figure chooses representative picture presentation result；Right side be statistical analysis figure, lymphocyte subgroup ratio be expressed as Mean ±
SD, Normal group n=10, disease group and P < 0.05 butyric acid intervention group n=18, * * P < 0.01, *.Tfh cell:T
Follicular helper cell, folliculus helper T lymphocyte；Treg cell:T regulatory cell, regulatory T are thin
Born of the same parents；
Fig. 7 is for butyric acid intervention to the regulation of joint draining lymph node lymphocyte subgroup as a result, lymphocyte subgroup ratio
It is expressed as Mean ± SD, every group of mouse n=8 is only；Th:T helper；GCB germinal center B；
Fig. 8 is for butyric acid intervention to the regulation of small intestine Patrick's knot lymphocyte subgroup as a result, percentage of lymphocyte is expressed as
Mean ± SD, every group mouse n=10, P < 0.01 * *；
Fig. 9 is influence of the butyric acid intervention to the species diversity of mouse intestinal flora, and wherein A figure is diversity indices
Shannon diversity, B figure is observable total Number of Species；OTU: can activity classification unit, P < 0.01 * *；
Figure 10 is that mark total ion chromatogram is mixed in embodiment 1.
Specific embodiment
The present invention provides application of the butyric acid in preparation prevention and/or treatment autoimmune disease drug.In this hair
In bright, mass content of the butyric acid in the drug for preventing and/or treating autoimmune disease is preferably 10~90%.Institute
Stating prevention and/or treating in the drug of autoimmune disease preferably further includes auxiliary material that butyric acid pharmaceutically receives；This hair
Bright type and dosage to the auxiliary material is not particularly limited, using the auxiliary material of this field routine.In the present invention, it is described from
Body immunity disease preferably includes systemic loupus erythematosus, rheumatoid arthritis and Sjogren syndrome.
The present invention provides application of the butyric acid in the drug that preparation inhibits the expression of autoantibody and proinflammatory factor.This hair
In bright, the proinflammatory factor preferably includes the IL-6 factor；The autoantibody is preferably the anti-II Collagen Type VI antibody of IgG type
anti-CII；In the present invention, the expression quantity of the autoantibody and proinflammatory factor is detected preferably through ELISA method；
In specific implementation process of the present invention, the antibody anti-CII is detected by anti-CII detection kit, and brand is
Chondrex, article No. Catalog#2036T；The detection of the proinflammatory factor preferably uses connection section biotechnology share to have
The cytokine detection kits of limit company.
The present invention provides application of the butyric acid in the drug that preparation promotes the expression of anti-inflammatory factors.It is described in the present invention
Anti-inflammatory factors preferably include the IL-10 factor.In the present invention, the expression quantity of the anti-inflammatory factors is preferably through ELISA method
It is detected；In specific implementation process of the present invention, the detection of the anti-inflammatory factors preferably uses connection section biotechnology share
The cytokine detection kits of Co., Ltd.
Drug, inhibition Tfh cell table the present invention provides butyric acid in preparation promotion joint lymph node Treg cell differentiation
Application in the drug reached and the drug for inhibiting GCB cell to express.The present invention is not particularly limited the dosage form of the drug,
Using this field conventional pharmaceutical dosage forms.In the present invention, the drug further includes the pharmaceutically acceptable auxiliary material of butyric acid.This hair
Butyric acid described in bright can promote local joint to rebuild immune homeostasis by regulating and controlling the expression of lymphocyte, thin by regulation lymph
The ratio of born of the same parents' subgroup and promote intestine immunity stable state rebuild.
The present invention provides application of the butyric acid in the drug that preparation adjusts serum short-chain fat acid content.The butyric acid is
For a kind of short chain fatty acids, the content of the short chain fatty acids in serum can be increased.
Technical solution provided by the invention is described in detail below with reference to embodiment, but they cannot be understood
For limiting the scope of the present invention.
Embodiment 1
Rheumatoid arthritis patients enteron aisle butyric acid content substantially reduces
24 normal persons and 30 rheumatoid arthritis patients are had detected using gas chromatography-mass spectrometry (GC-MS)
The content of RA excrement Short-Chain Fatty Acids.Method is as follows:
1. standard items configuration and pre-treatment
Precise acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid and the pure standard items of caproic acid, are matched with ethyl acetate
It is set to 0.5 μ g/mL, 1 μ g/mL, 5 μ g/mL, 10 μ g/mL, 20 μ g/mL, 50 μ g/mL, 100 μ g/mL, 200 μ g/mL eight mixing
Normal concentration gradient.The standard items of 600 μ L are taken, final concentration of 500 μM of isocaproic acid is added as internal standard, mixes and sample introduction is added
Bottle is detected to gas chromatograph-mass spectrometer (GC-MS) (Gas Chromatography-Mass Spectrometer) GC-MS.
2. sample pre-treatments
Sample is thawed on ice, the accurate 100mg sample that measures is in 2mL glass centrifuge tube.It is added 1000 μ L's 0.5%
Phosphoric acid is resuspended, and concussion mixes 2min；17949g is centrifuged 10min, takes 800 μ L of supernatant, and the ethyl acetate that equivalent is added extracts,
Concussion mixes 2min, and 17949g is centrifuged 10min；600 μ L upper organic phases are taken, final concentration of 500 μM of 4- methylvaleric acid is added
It as internal standard, mixes and sample injection bottle is added, detected to GC-MS.
3.GC-MS detects program
3.1 chromatographic conditions: chromatographic column agilent DB-WAX capillary column (30m*0.25mm ID*0.25um)；It is diverted into
Sample, sample volume 1 μ L, split ratio 10:1.250 DEG C of injector temperature；230 DEG C of ion source temperature；250 DEG C of transmission line temperature, quadrupole
150 DEG C of bar temperature.90 DEG C of temperature programming initial temperature；Then 120 DEG C are warming up to 10 DEG C/min；It is warming up to again with 5 DEG C/min
150℃；250 DEG C of maintenance 2min are finally warming up to 25 DEG C/min.Carrier gas is helium, flow rate of carrier gas 1.0mL/min.
3.2MS condition: the source electron impact ionization (EI) is swept and SIM scanning mode, electron energy 70eV entirely.
4. method validation
4.1 mixed marks total ion chromatogram (TIC)
TIC figure shows, 8 short chain fatty acids can be distinguished as shown in Figure of description 10 from TIC chart.Wherein
Internal standard (isocaproic acid) appearance time is 7.243min, has with other short chain fatty acids standard items and is clearly separated, shows that method is good
It is good.
4.2 standard curves and the range of linearity
GC-MS detection is carried out respectively to the concentration series of short-chain fat standard acid solution, with the concentration of standard variety each component
For abscissa, peak area/interior is designated as ordinate, investigates the linear of standard solution with this.The linear regression of obtained each ingredient
Equation is shown in Table 1.Coefficient R2> 0.99.
Equation of linear regression, precision and the quantitative limit of 17 kinds of short chain fatty acids standard items components of table
Accuracy: standard sample continuous sample introduction 6 times on GC-MS respectively for being 200 μ g/mL by mixed mark concentration, and to every
Kind component and interior target ratio calculation precision.The relative standard deviation (RSD) of each component exists in short chain fatty acids standard solution
Between 0.53%~2.60%, show that the precision of instrument is good.
Repeatability: the same sample is reprocessed into six parts of sample introductions on GC-MS respectively, calculates the concentration of every kind of component.
The relative standard deviation (RSD) of each component concentration shows repeated good between 3.26%~13.67%.
The results show that being compared with normal people, butyric acid and caproic acid content substantially reduce (butyric acid group But 1145 in Intestinal Mucosal Injury in Patients Undergoing
± 643.2vs disease control group CIA 760.4 ± 438), other short chain fatty acids (acetic acid, propionic acid, isobutyric acid, valeric acid, isoamyls
Acid) without significant change, (see Fig. 1, wherein A~G is respectively butyric acid, caproic acid, acetic acid, propionic acid, isobutyric acid, valeric acid, isoamyl to content
Acid).It is closely related with rheumatoid arthritis morbidity that this illustrates that butyric acid is reduced.
Embodiment 2
Butyric acid Inhibition test arthritis occurrence and development
Method:
Butyric acid is studied to the prevention effect of experimental arthritis, administration time is first day to after immune the after initial immunity
38 days, butyric acid is added in mouse feed and is fed, the additive amount of butyric acid is 20wt%.Control group mice feeding is normal to raise
Material.Disease incidence record: (i.e. after initial immunity the 22nd day) starts observation mouse arthritis incidence daily after booster immunization,
Record disease time and disease incidence, disease incidence=(morbidity mouse number of elements/total mice) * 100.Arthritis score: observation mouse
Arthroncus situation, scores.Scoring is carried out by 2 experimenters are independent simultaneously, and the average value for taking two people to score is as most
Final review point.Scoring joint includes front and back limb totally four podarthrums of mouse, and each Joint scores standard, as follows: swelling toe is few
It is 1 point in being equal to 2, more than two is 2 points, and sole swelling is 1 point, and ankle swelling is 1 point.Each joint highest 4 is divided, and every
Mouse highest 16 is divided.
As a result as shown in Figure 2 A and 2 B, Fig. 2 illustrate 2 independent experiments as a result, disease incidence and arthritis score table
Be shown as Mean ± SEM, every group of mouse n=18 only, P < 0.01 * *.CIA:collagen-induced arthritis, collagen lure
The property led arthritis；But:butyrate, butyric acid.It can be seen that butyric acid can make experimental arthritis disease incidence decline 74% (Fig. 2A, morbidity
Rate butyric acid group But 11%vs disease control group CIA 85%) and arthritis score is significantly reduced, inhibit Arthritis development (figure
2B, arthritis score But 0.26vs CIA 6.7).Meanwhile computed tomography (CT) imaging and histopathological analysis
The results show that butyric acid feed can inhibit inflammatory cell infiltration synovial tissue of joint, and Saving cortilage bone tissue is from erosion damage
(Fig. 3 and 4, histopathology scoring 0.1833 ± 0.2687vs of But CIA 1.865 ± 1.12；4 claws of every mouse in Fig. 4
Make HE and dye and carry out pathological score, takes the average mark of four claws.Pathological score is expressed as Mean ± SD, every group of mouse n
P < 0.01=8, * *.CIA: disease group；CIA+But: butyric acid intervention group).
Butyric acid promotes joint lymph node Treg cell differentiation and Tfh cell is inhibited to express.Gut region is immunoreacted in class
There is key regulatory effect in rheumathritis morbidity.In Patrick's knot (peyer ' s patches, PP) and lymphonodi mesenterici
The testing result of lymphocyte subgroup shows that the ratio of Tfh and GCB cell is significantly raised in CIA mouse Patrick's knot, and butyric acid
It then can inhibit the expression of Tfh and GCB, and promote Treg cell differentiation.In lymphonodi mesenterici, butyric acid group Treg cell has
The trend of up-regulation, the ratio of Tfh and Th1 cell have the tendency that reduction, GCB and Th17 cell is without significant change.The above results table
Bright, butyric acid promotes intestine immunity stable state to rebuild by regulating and controlling the ratio of lymphocyte subgroup.
Embodiment 3
Intestine immunity balance is adjusted in butyric acid
(1) butyric acid inhibits autoantibody and proinflammatory factor to express and anti-inflammatory factors is promoted to secrete
Acquire mouse peripheral blood, separate serum, ELISA method detect the anti-II Collagen Type VI antibody (anti-CII) of IgG type and
The content of cell factor.Detection method is operated in accordance with kit specification, first carries out the clear Sample Dilution multiple of trial test,
It is formally tested again.CII kit brand is Chondrex, article No. Catalog#2036T；Cell factor kit brand
For connection section.
The results show that the anti-CII antibody expression amount of butyric acid intervention group significantly reduce (Fig. 5 A, butyric acid group 17520 ±
4400vs disease control group CIA22385 ± 1856), show that butyric acid can inhibit autoantibody generation.Cytokines measurement result is aobvious
Show, the expression that butyric acid intervention group presses down scorching factor IL-10 dramatically increases (Fig. 5 B, butyric acid group 111.9 ± 55.42vs disease control group
CIA53.1 ± 26.58), and the synthesis of proinflammatory factor IL-6 significantly reduces (Fig. 5 C, butyric acid group 41.88 ± 49.81vs disease pair
According to group CIA 87.37 ± 81.31).Butyric acid is to other inflammatory mediators such as IL-17, and the expression of TNF-α and TGF-β is without obvious shadow
It rings.Result above prompt, butyric acid may have immunoregulation effect to experimental arthritis, and it is relevant immune to can inhibit arthritis
Inflammatory reaction.
(2) butyric acid promotes joint lymph node Treg cell differentiation and Tfh cell is inhibited to express
In order to which immunoregulation of the clear butyric acid to experimental arthritis acts on, we have detected mouse spleen and joint drainage
Area's lymph node (popliteal nest and armpit) lymphocyte subsets expression.Testing result is shown, compared with normal mouse, disease
The ratio of T effector cell Tfh (T follicularhelper) dramatically increases in the lymph node of group (CIA) mouse joint, and fourth
Acid intervenes expression (Fig. 6 A, butyric acid group 3.232 ± 0.8794vs disease control group CIA 4.983 that then can obviously lower Tfh cell
±2.195).Meanwhile disease group mouse joint lymph node regulatory T cells Treg (T regulatory) cell feedback liter
Height, and butyric acid intervention can then be dialled further up it and express (Fig. 6 B, butyric acid group 8.971 ± 1.56vs disease control group CIA 7.356
±1.433).Butyric acid is to auxiliary T (T helper) cell Th1, Th17 and centrum germinativum B (germinal in the lymph node of joint
CenterB, GCB) cell is without obvious regulating and controlling effect (Fig. 7).Result above prompt, butyric acid can pass through the expression of regulation lymphocyte
And local joint is promoted to rebuild immune homeostasis.
(3) butyric acid promotes enteron aisle Treg cell differentiation and inhibits the expression of Tfh and GCB cell
Gut region immune response has key regulatory effect in rheumatoid arthritis morbidity.Patrick's knot (peyer ' s
Patches, PP) and the testing result of lymphonodi mesenterici lymphocyte subsets show, in CIA mouse Patrick's knot Tfh and
The ratio of GCB cell is significantly raised, and butyric acid then can inhibit Tfh (Fig. 8 B, butyric acid group 1.89 ± 0.9682vs disease control group
CIA 6.147 ± 2.672) and GCB (Fig. 8 C, butyric acid group 7.402 ± 7.509vs disease control group CIA 18.97 ± 5.536)
Expression, and promote Treg cell differentiation (Fig. 8 A, butyric acid group 6.275 ± 1.522vs disease control group CIA 3.363 ±
1.997).The above results show that butyric acid promotes intestine immunity stable state to rebuild by regulating and controlling the ratio of lymphocyte subgroup.
Embodiment 4
Butyric acid can also increase the species diversity of intestinal flora, be enriched with related probiotics, adjust intestinal flora balance.
Enteric flora disturbance is fallen ill closely related with rheumatoid arthritis.Using biochip technology, enteric bacteria is utilized
Target gene chip of the 16S ANA gene as monitoring, detection mouse intestinal flora 16S rRNA sequencing analysis is as a result, research is aobvious
Show, butyric acid can dramatically increase the species richness and diversity (Fig. 9) of intestinal flora.Meanwhile butyric acid intervention group mouse intestinal
The composition of flora is also substantially change, and the bacterium of Bifidobacterium and streptococcus is in butyric acid group significant enrichment.Above-mentioned knot
Fruit prompt, butyric acid have regulating and controlling effect, and the variation that the variation of intestinal flora may be reacted with intestine immunity to intestinal flora
It is related.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. application of the butyric acid in preparation prevention and/or treatment autoimmune disease drug.
2. application according to claim 1, which is characterized in that the medicine of the prevention and/or treatment autoimmune disease
It further include the auxiliary material that butyric acid pharmaceutically receives in object.
3. application according to claim 1 or 2, which is characterized in that the butyric acid is preventing and/or treating autoimmune
Mass content in the drug of disease is 10~90%.
4. application of the butyric acid in the drug that preparation inhibits the expression of autoantibody and proinflammatory factor.
5. application according to claim 4, which is characterized in that the proinflammatory factor includes the IL-6 factor.
6. application of the butyric acid in the drug that preparation promotes the expression of anti-inflammatory factors, which is characterized in that the anti-inflammatory factors include
The IL-10 factor.
7. application of the butyric acid in the drug that preparation promotes joint lymph node regulatory T cells Treg differentiation.
8. application of the butyric acid in the drug that preparation inhibits folliculus helper T lymphocyte Tfh expression.
9. application of the butyric acid in the drug that preparation inhibits Germinal center B cell GCB expression.
10. application of the butyric acid in the drug that preparation adjusts serum short-chain fat acid content.
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| CN110283754A (en) * | 2019-07-11 | 2019-09-27 | 中国科学院北京基因组研究所 | For the assessment of rheumatoid arthritis inflammatory conditions and the intestinal microflora of prognostic evaluation |
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| CN102670663A (en) * | 2008-01-31 | 2012-09-19 | 青岛东海药业有限公司 | Clostridium preparation and application thereof |
| CN107636146A (en) * | 2015-03-02 | 2018-01-26 | 同生公司 | Bacteria engineered to treat diseases benefiting from reduced gut inflammation and/or tightened gut mucosal barrier |
| WO2018027274A1 (en) * | 2016-08-10 | 2018-02-15 | Monash University | Metabolites for treatment and prevention of autoimmune disease |
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2019
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670663A (en) * | 2008-01-31 | 2012-09-19 | 青岛东海药业有限公司 | Clostridium preparation and application thereof |
| CN107636146A (en) * | 2015-03-02 | 2018-01-26 | 同生公司 | Bacteria engineered to treat diseases benefiting from reduced gut inflammation and/or tightened gut mucosal barrier |
| WO2018027274A1 (en) * | 2016-08-10 | 2018-02-15 | Monash University | Metabolites for treatment and prevention of autoimmune disease |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283754A (en) * | 2019-07-11 | 2019-09-27 | 中国科学院北京基因组研究所 | For the assessment of rheumatoid arthritis inflammatory conditions and the intestinal microflora of prognostic evaluation |
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