CN109793760A - Succinivibrio is preventing or is treating the purposes in the medicine of plateau - Google Patents
Succinivibrio is preventing or is treating the purposes in the medicine of plateau Download PDFInfo
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Abstract
The present invention provides application of the Succinivibrio in preparation prevention or treatment plateau medicine, and the altitude sickness is the acute high altitude sickness generated under altitude environment more than height above sea level 2000m and chronic plateau sickness.
Description
Technical field
The invention belongs to biomedicine fields, and in particular to Succinivibrio is in preparation prevention or treatment plateau medicine
In application.
Background technique
Altitude environment rarefaction of air, atmospheric pressure and oxygen are forced down, and very cold is dry, and ultraviolet radiation is strong.It is moved by Plain
The people for occupying to plateau or being stayed in short term on plateau, because causing one using anoxic as outstanding behaviours to altitude environment adaptability deficiency
Group disease is known as altitude sickness, and symptom normally behaves as headache, palpitation, tired, uncomfortable in chest, shortness of breath, vomiting, appetite stimulator, twitch, meaning
Know in a trance, cognitive ability rapid drawdown etc..Sign is increased heart rate, exaggerated respiration, blood pressure mile abnormality, face or edema of limbs, mouth
Purple lips dark purple etc..
It is mainly at present acetazolamide for altitude sickness prevention and treatment common drug, the medicine is by inhibiting carbonic anhydrase activity to play
Effect, the effect of carbonic anhydrase are that carbon dioxide and water is promoted to be combined into carbonic acid, increase cerebral blood flow (CBF) and reduce the production of cerebrospinal fluid
It is raw, while making organism metabolism meta-acid, to fight the alkalemia generated by hyperpnea.But for acclimatization and adapt to anoxic energy
The raising of power is limited always, and internal anaerobic environment as time went on can get over the damage of nervous system there is no improving
Come more serious, sleepy, facial and numb limb occur, long with that can cause metabolic acidosis and hypopotassaemia, more it is serious not
Good reaction is the allergic reactions such as agranulocytosis and kidney stone.
Drugs or the relevant healthcare product such as root of kirilow rhodiola, plateau peaceful, American Ginseng, Radix Salviae Miltiorrhizae ball, Bufferin are disclosed in the prior art
Prevent or treat altitude sickness in application, such as patent CN103829245A, CN103948896A, CN104274808A,
CN104288262A、CN104288735A、CN104288476A、CN104721202A、CN104706771A、
CN105168308A, CN105193839A etc., but these drugs or food there are slow effect, side effect is more the defects of.
Succinivibrio category proteus door, Succinivibrio section, metabolizable generation acetic acid and succinic acid, participate in dimension life
The synthesis of the anti-inflammatory substances such as element has potential anti-inflammatory and cardiovascular protective effect.
People's intestinal flora and its metabolite can enter blood circulation through intestinal mucosa, play physiology and pathophysiological role.
Flora transplanting is proved that treatment part disease of digestive system can be played the role of.But so far, there is not yet Succinivibrio
Report applied to altitude sickness.
Summary of the invention
An object of the present invention is to provide use of the Succinivibrio in preparation prevention or treatment altitude sickness product
On the way.
In a first aspect, the present invention provides application of the Succinivibrio in preparation prevention or treatment plateau medicine.
The Succinivibrio includes succinovibrio dextrinosolvens (Succinivibrio
dextrinosolvens)。
In the specific embodiment of the present invention, the Succinivibrio in the Succinivibrio is provided
Application of the dextrinosolvens in preparation prevention or treatment plateau medicine.
The altitude sickness is selected from the acute high altitude sickness generated under altitude environment and chronic plateau sickness.
Preferably, the altitude environment is height above sea level 2000m or more, has low pressure, the condition of anoxic.
It is further preferred that the altitude environment is height above sea level 2700m or more, under conditions of low pressure, anoxic.
In the specific embodiment of the present invention, the altitude environment be height above sea level 3500m or more, have low pressure,
Under conditions of anoxic.
In the specific embodiment of the present invention, the altitude environment be height above sea level 5500m or more, have low pressure,
Under conditions of anoxic.
The acute high altitude sickness includes but is not limited to altitude coma, plateau brain edema, plateau pneumochysis, plateau retina
Bleeding or the simultaneous mixed type disease of brain lung abnormal symptom.
Chronic plateau sickness of the present invention includes but is not limited to plateau heart disease, altitude erythrocytosis, plateau height
The simultaneous mixed type disease of blood pressure, high altitude hypotension, plateau heart disease, polycythemia.
Preferably, the altitude sickness is anti-plateau cardiopulmonary and injury of blood vessel；It is further preferred that the altitude sickness is
Plateau heart disease.
In a specific embodiment of the invention, the plateau heart disease includes pulmonary hypertension, right ventricle expansion, fills
Hemorrhagic right heart failure, right ventricle plumpness or right heart insufficiency.
Preferably, the clinical manifestation of the altitude sickness is selected from headache, giddy, palpitation, increased heart rate, tired, uncomfortable in chest, gas
Short, exaggerated respiration, insomnia, out of strength, dim eyesight, drowsiness, appetite stimulator, twitch, realizes in a trance, numb in every limb, lip at Nausea and vomiting
Refer to the combination of one or more of cyanosis, face oedema, edema of limbs or cognitive ability rapid drawdown.
Second party is bright, and the present invention provides a kind of pharmaceutical composition, contains Succinivibrio in the pharmaceutical composition
And pharmaceutically acceptable auxiliary material, the pharmaceutical composition can be used for preventing or treating altitude sickness.
The Succinivibrio includes succinovibrio dextrinosolvens (Succinivibrio
dextrinosolvens)。
The pharmaceutically acceptable auxiliary material be selected from carrier, excipient, diluent, lubricant, wetting agent, emulsifier,
Preservative, antioxidant, buffer, bacteriostatic agent, the solute for keeping the blood of preparation and recipient isotonic, suspending agent, suspending agent, increasing
The combination of one or more of solvent, thickener, stabilizer, sweetener and fragrance.
The pharmaceutically acceptable auxiliary material be selected from lactose, glucose, sucrose, D-sorbite, mannose, starch, I
Primary glue, calcium phosphate, alginates, gelatin, calcium silicates, fine crystallization cellulose, cellulose, water, syrup, methylcellulose, hydroxy benzenes
The combination of one or more of methyl formate, nipasol, talcum, magnesium stearate and mineral oil.
It is 1 × 10 to rat oral gavage concentration in simulated high altitude environment in the specific embodiment of the present invention7-
9×108Cfu/ml Succinivibrio bacterium solution has the effect of improving the pulmonary hypertension and Right ventricular hypertrophy of rat.
The dosage form of described pharmaceutical composition can be syrup, elixir, suspending agent, pulvis, granule, tablet, glue
Capsule, pastille, aqueous solution, creme, paste, lotion, gelling agent, emulsion etc..
Pharmaceutical preparation is preferably unit dosage forms.In this form, said preparation is subdivided into the activity comprising amount appropriate
The unit dose of component.Unit dosage forms can be packaged preparation, which contains the preparation of discrete amount, such as be packaged in
Tablet, capsule and pulvis in bottle or ampoule.In addition, unit dosage forms can be capsule, tablet or its can be and wrapping
An appropriate number of any of these dosage forms in dress form.
In unit dose formulations the amount of active component can from 0.1 milligram to 1000 milligram be altered or modified, according to work
Depending on the concrete application and effect of property component.If desired, composition also may include other suitable therapeutic agent.
Pharmaceutical acceptable carrier partly according to concrete composition depending on, and according to the specific medication of composition and
It is fixed.Therefore, there are various preparations appropriate for pharmaceutical composition of the invention.
Such as passing through intravenous, intramuscular, intradermal and subdermal routes of administration preparation suitable for parenteral routes includes containing
Water and non-aqueous isotonic sterile injection liquid, may include antioxidant, buffer, bacteriostatic agent, and make preparation and the blood of recipient
The isotonic solute of liquid and aqueous and non-aqueous sterile suspensions, may include suspending agent, solubilizer, thickener, stabilizer and
Preservative.In the practice of the invention, composition can be for example, by venoclysis, orally, part, in peritonaeum, in bladder and sheath
Interior administration.The preparation of compound may be present in unit dose or multi-dose sealing container such as ampoule and bottle.Injection
Solution liquid and suspension can be prepared from the sterile powder, particle and tablet of previously described type.
In the context of the present invention, object dosage is given with should generate beneficial control in subject with the time enough
Iatreusiology response.Dosage by the weight of the effect of particular compound used and the patient's condition of object and object to be treated or
Depending on body surface area.The size of dosage will be made according in specific object with any unfavorable pair that particular compound administration generates
Depending on presence, property and degree.Compound to be administered is determined in the treatment or prevention of just treated illness
The factors such as in effective quantity, the circulating plasma that doctor can evaluate compound is horizontal, toxicity of compound and/or disease process and
It is fixed.
The third aspect, the present invention provide a kind of food, contain the Succinivibrio and food in the food
Acceptable auxiliary material on.The food has the effect of preventing or treating altitude sickness.
The Succinivibrio includes succinovibrio dextrinosolvens (Succinivibrio
dextrinosolvens)。
The type of food of the present invention is not particularly limited, and can be any of food, for example, dairy produce,
Biscuit, cake, beverage, health care product etc..
The food is selected from least one of solid, dairy products, solution product, pulverulent product and suspension product form.
In the bromatology acceptable auxiliary material be selected from carrier, excipient, diluent, lubricant, wetting agent, emulsifier,
The combination of one or more of suspension stabiliser, preservative, sweetener and fragrance.
According to an embodiment of the invention, acceptable auxiliary material is selected from lactose, glucose, sucrose, sorb in the bromatology
Sugar alcohol, mannose, starch, Arabic gum, calcium phosphate, alginates, gelatin, calcium silicates, fine crystallization cellulose, cellulose, water, sugar
One of slurry, methylcellulose, methyl hydroxybenzoate, nipasol, talcum, magnesium stearate and mineral oil or two
Kind or more combination.
Fourth aspect, the reagent that the present invention provides detection Succinivibrio are resistant in the case where individual altitude environment is assessed in preparation
The application of the product of ability.
Preferably, the Succinivibrio is the Succinivibrio in enteron aisle.
The Succinivibrio includes succinovibrio dextrinosolvens (Succinivibrio
dextrinosolvens)。
Preferably, the reagent of the detection Succinivibrio is the reagent for detecting Succinivibrio abundance.
Preferably, the reagent of the detection Succinivibrio is the Succinivibrio abundance detected in individual enteron aisle
Reagent.
In the specific embodiment of the present invention, the reagent of the detection Succinivibrio is to detect individual excrement
Just the reagent of the Succinivibrio abundance in.
Preferably, the product of tolerance includes detection Succinivibrio abundance under the individual altitude environment of the assessment
Reagent.
Preferably, the altitude environment is height above sea level 2000m or more, has low pressure, the condition of anoxic.
It is further preferred that the altitude environment is height above sea level 2700m or more, under conditions of low pressure, anoxic.
In the specific embodiment of the present invention, the altitude environment be height above sea level 3500m or more, have low pressure,
Under conditions of anoxic.
In the specific embodiment of the present invention, the altitude environment be height above sea level 5500m or more, have low pressure,
Under conditions of anoxic.
Tolerance is the susceptible degree of altitude sickness under altitude environment of the present invention.
Detailed description of the invention
Fig. 1 show the difference of the relative abundance of Succinivibrio in the Chinese Tibetan enteron aisle group that box figure is shown；
Fig. 2 show the sensibility and specificity of tolerance under Succinivibrio relative abundance assessment altitude environment
ROC curve；
Fig. 3, which is shown, carries out Succinivibrio dextrinosolvens10 to rat6(A group), 107(B group), 108
(C group), same amount of normal saline (D, E group) stomach-filling, and the altitude environment by A, B, C, D group rat at 5500 meters of altitude simulating simultaneously
Raising 28 days, after E group is raised 28 days under the normal oxygen environment of normal pressure, the variation of each group Pulmonary Hypertension (mPAP)；
Fig. 4, which is shown, carries out Succinivibrio dextrinosolvens10 to rat6(A group), 107(B group), 108
(C group), same amount of normal saline (D, E group) stomach-filling, and the altitude environment by A, B, C, D group rat at 5500 meters of altitude simulating simultaneously
Raising 28 days, after E group is raised 28 days under the normal oxygen environment of normal pressure, each group rat RV ejection fraction (RVEF) and right ventricle shorten
The variation of score (RVFS):
Fig. 4 a show the variation of each group rat RVEF；
Fig. 4 b show the variation of each group rat RVFS；
Fig. 5, which is shown, carries out Succinivibrio dextrinosolvens10 to rat6(A group), 107(B group), 108
(C group), same amount of normal saline (D, E group) stomach-filling, and the altitude environment by A, B, C, D group rat at 5500 meters of altitude simulating simultaneously
Raising 28 days, after E group is raised 28 days under the normal oxygen environment of normal pressure, the variation of each group rat RV/ (LV+OS).
Fig. 6 is group's composition in Tibetan soldier group (Zang) excrement.
Fig. 7 Han nationality soldier (Han) organizes group's composition in excrement.
Specific embodiment
1 plains region crowd of embodiment and highlands Intestinal bacterium abundance difference
One, materials and methods:
1.1 study population
Design case-control study is stated according to STROBE, is included in certain moon in year to certain moon in year and is on active service in certain Chinese army
Tibetan male soldiers more than 128 acclimatization height above sea level, 3500 meters of plateaus is experimental group, flat according to Tibetan's soldier's age-matched 128
Former Han nationality soldier compares.The identical Chinese army mixed diet of the carry out of two groups of crowds of strict control, keeps identical sea
3500 meters of training environments and training strength are pulled out, smoking cessation, wine continue 3 months.Exclusion has chronic inflammatory disease, oral antibiotic, urgency
Sexuality dye and enterogastric diseases taxi soldier.
1.2 fecal specimens are collected
Each research object receives a closestool excrement collector after being included in, big after an action of the bowels by stool loading in discharge
Collecting dung pipe is stored in -20 DEG C of refrigerators at once, and stool sample is transported to -80 DEG C of refrigerators and saved by next day, and unified storage is standby
With.
1.3 DNA are extracted
Absorption 1000ul cetyl trimethylammonium bromide (Hexadecyl trimethyl ammonium Bromide,
CTAB) in lysate to 2.0ml EP pipe, lysozyme is added, the sample of 500ul or so is added in lysate, 65 DEG C of water-baths,
Period is mixed by inversion for several times, so that sample sufficiently cracks.Centrifuging and taking supernatant adds phenol (pH8.0): chloroform: isoamyl alcohol (25:24:
1) it, is mixed by inversion, 12000rpm is centrifuged 10min.Take supernatant, chlorination is imitative: isoamyl alcohol (24:1) is mixed by inversion, 12000rpm from
Heart 10min.It draws in supernatant to 1.5mL centrifuge tube, isopropanol is added, rocks up and down, -20 DEG C of precipitatings.12000rpm centrifugation 10
Minute, liquid is poured out, is careful not to pour out precipitating.With 75% ethanol washing of 1ml 2 times, remaining a small amount of liquid can be centrifuged again
It collects, is then sucked out with pipette tips.Superclean bench drying or room temperature are dried.DdH is added2O dissolving DNA sample, adds RNase A
1ul digests RNA, 37 DEG C of placement 15min.Later using the purity and concentration of agarose gel electrophoresis detection DNA, suitable sample is taken
This DNA uses sterile water diluted sample to 1ng/ μ l in centrifuge tube.
1.4 PCR amplifications, sample mixing and purifying
Using the genomic DNA after diluting as template, according to sequencing region 16S V3-V4, selection uses the spy with Barcode
Different primer:
515F:5 '-GTGCCAGCMGCCGCGGTAA-3 ' (SEQ ID NO:1),
806R:5 '-GGACTACHVGGGTWTCTAAT-3 ' (SEQ ID NO:2), New England Biolabs company
'sHigh-Fidelity PCR Master Mix with GC Buffer, and efficient high fidelity enzyme (Taq DNA Polymerase) carry out PCR, it is ensured that amplification efficiency and accuracy.
PCR product carries out electrophoresis detection using the Ago-Gel of 2% concentration；It is mixed that equivalent is carried out according to PCR product concentration
Sample uses the agarose gel electrophoresis purified pcr product of 1 × TAE concentration 2%, shearing recycling target stripe after mixing well.Product
Purification kit uses Thermo Scientific company GeneJET plastic recovery kit recovery product.
1.5 library constructions and the sequencing of upper machine
Library kit is built using the Ion Plus Fragment Library Kit 48rxns of Thermofisher company
The building in library is carried out, the library built uses Thermofisher's after Qubit is quantitative and library detection is qualified
Ion S5TMXL carries out machine sequencing.
The analysis of 1.6 data
1.6.1 sequencing data is handled
It is first right using Cutadapt (V1.9.1, http://cutadapt.readthedocs.io/en/stable/)
Reads carries out low quality Partial Shear, splits out each sample data from obtained reads further according to Barcode, clips
Barcode and the preliminary Quality Control of primer sequence obtain initial data, and the Reads obtained after handling above needs to be removed embedding
The processing of fit sequence, Reads sequence are finally removed by the way that detection chimera sequence is compared with species annotations database
Chimera sequence therein, obtains final valid data.
1.6.2 taxonomical unit (operational taxonomic unit, the OUT) cluster and species annotation of operation
Using Uparse software (Uparse v7.0.1001, http://www.drive5.com/uparse/) to all
Whole valid data of sample are clustered, and Sequence clustering is become OTUs (Operational with 97% consistency by default
Taxonomic Units), while the representative series of OTUs can be chosen, according to its algorithm principle, screening is that occur in OTUs
Representative sequence of the highest sequence of frequency as OTUs.Species annotation is carried out to OTUs sequence, with Mothur method and SILVA
The SSUrRNA database of (http://www.arb-silva.de/) carries out the analysis of species annotation (given threshold is 0.8~1),
It obtains taxonomic information and forms (see Fig. 6,7) in the group for belonging to level statistic Han nationality soldier's group, Tibetan soldier group respectively.
1.6.3 the calculating of Pseudomonas relative abundance and comparison in difference
Pseudomonas relative abundance with Succinivibrio OTU value/detection pattern detection to all Pseudomonas OTU values indicate, it is poor
Different comparison is because sample Non-Gaussian Distribution is examined using Mann-Whitney.ROC curve assessment Pseudomonas relative abundance is drawn to height
The antidiastole sensibility and specificity of former Chinese Han Population and Tibetan populations, calculates dividing value, and P < 0.05 is that difference has statistics meaning
Justice carries out statistical procedures using SPSS22.0 software package.
Two, experimental result
Succinivibrio relative abundance difference in 2.1 Han nationality on plateau and Tibetan populations stool sample
By the way that hiding group soldier and Han nationality soldier enteron aisle Succinivibrio 16sRNA sequencing, result is amber in Chinese Han Population
The relative abundance [median (quartile)] of amber acid vibrio is [4.17 × 10-5(0,1.66 × 10-4)], Tibetan clansman
The relative abundance [median (quartile)] of Succinivibrio is [1.49 × 10 in group-4(7.72×10-5, 3.13 × 10-4)], Tibetan populations Succinivibrio relative abundance is significantly higher than Chinese Han Population, as shown in Figure 1.
2.2 Succinivibrio relative abundances assess the sensibility and specificity of tolerance under altitude environment
By Fig. 2's, the result shows that, ROC curve shows that crowd's Chinese hiding in Succinivibrio relative abundance antidiastole plateau is come
AUC (area under the ROC curve) value in source is 0.933, is 5.62 × 10 in Pseudomonas relative abundance-5When, it can be obtained and maximum about step on
Index 0.863, susceptibility and specificity are respectively 0.874 and 0.956, accuracy 0.914, and F1 score is 0.912.
The above results show that detection stool sample Succinivibrio relative abundance is sequenced using 16SrRNA, it is possible to authenticate
Plateau crowd source is Tibetan or Han nationality, alternatively, assessment individual works as Succinivibrio for tolerance under altitude environment
Relative abundance is greater than 5.62 × 10-5It can determine that individual is very strong for tolerance under altitude environment, it is possible to itself be Tibetan
People.
Influence of the 2 Succinivibrio dextrinosolvens of embodiment to plateau heart disease rat model
Experimental animal: SD rat ties up experimental animal Co., Ltd, tonneau China purchased from Beijing
Test method:
Male cleaning grade SD rat 60 of 200g or so are taken, low-pressure oxygen cabin raising is periodically given full nutrition feed and fed
Food, 22-25 DEG C of room temperature, humidity 50%-70%.
Succinivibrio dextrinosolvens is cultivated (LB culture medium), it is isolated after 3000g centrifugation
Bacterial precipitation object takes 1 × 10 through preliminary experiment decision respectively6cfu/ml、1×107cfu/ml、1×108Cfu/ml is (by bacterial suspension
In the physiological saline of 300uL) intervene respectively.
60 rats are randomly divided into 5 groups, respectively A group, B group, C group, D group and E group, every group 12.A group, B group, C
The normal Plain environment raising of group, D group and E group rat, does following processing in 7 days continuous to each group rat:
A group rat carries out 1 × 106Cfu/ml Succinivibrio dextrinosolvens stomach-filling；
B group rat carries out 1 × 107Cfu/ml Succinivibrio dextrinosolvens stomach-filling；
C group rat carries out 1 × 108Cfu/ml Succinivibrio dextrinosolvens stomach-filling；
D, E group rat injecting normal saline,
Once a day.Tetra- groups of rats of A, B, C, D are placed in Multi-factor overlap environmental simulation medical science Laboratory Module after 7 days
In, pressure is to 380mmHg in adjusting cabin, the altitude environment that 5500 meters of altitude simulating, opens Laboratory Module 1 hour daily, to give
Animal adds feed and water, while being kept for environment 12:12 hours locating for rat day alternates with night, continues 28 days.E group rat is placed on
It is raised under the normal oxygen environment of normal pressure in same room.
With 3% yellow Jackets, 0.2ml/100g intraperitoneal injection of anesthesia rat, row ultrasound detection, blood is penetrated by measurement right ventricle
Score (RVFS) shortens in score (RVEF) and right ventricle.Rat dorsal position is fixed on operating table later, trachea cutting-pipe, connection is exhaled
Suction machine opens chest, exposure heart, and conduit is inserted into right ventricle, and row right cardiac catheterization measures mean pulmonary arterial pressure (mPAP).It puts to death
Rat takes out heart, removes atrial tissue and attachment fat, separates left and right ventricles, filter paper suck dry moisture is weighed respectively, is measured
Right ventricle's specific gravity (RV/ (LV+OS)).
All data indicate that comparison among groups are one-way analysis of variance with x ± s, and P < 0.05 is that difference has statistics meaning
Justice carries out statistical procedures using SPSS22.0 software package.
Test result
1, influence of the bacterium solution to rat mPAP
After hypobaric hypoxia environment is raised 28 days, the mPAP of rat is significantly raised, and difference has conspicuousness (P < 0.01),
Illustrate that hypobaric hypoxia environment can make the right heart of normal rat that failure occur.But under hypobaric hypoxia environment, with normal E group
I.e. normal rat is compared, and the mPAP of B, C group rat is significantly lower than D group, and B group is lower than C group but difference is without obvious statistical significance,
As shown in figure 3, rat oral gavage Succinivibrio dextrinosolvens can be effectively reduced because altitude environment produces in explanation
Raw mPAP.
2, influence of the bacterium solution to rat RVEF and RVFS
Fig. 4 show rat after hypobaric hypoxia environment is raised 28 days, the variation of each group rat RVEF and RVFS, Fig. 4 a institute
It is shown as the variation of each group rat RVEF, Fig. 4 b show the variation of each group rat RVFS.It is learnt by data in figure, with normal E
Group is that normal rat is compared, and the RVEF and RVFS of B group rat are without significant difference, and the RVEF and RVFS of A, C, D group rat are compared with B, E
Group is substantially reduced, and it is anisotropic (P < 0.05) to have significance difference, and RVEF the and RVFS ratio A group of C group rat is high, illustrate with 1 ×
107-1×108Cfu/ml Succinivibrio dextrinosolvens stomach-filling is to heart caused by the hypobaric hypoxia environment of plateau
Structure function is impaired therapeutic effect, especially 1 × 107Cfu/ml Succinivibrio dextrinosolvens has more preferably
Therapeutic effect.
3, influence of the bacterium solution to rat RV/ (LV+OS)
Fig. 5 is shown after hypobaric hypoxia environment is raised 28 days, the variation of each group rat RV/ (LV+OS), A, B, C, D group
The RV/ (LV+OS) of rat is significantly raised compared with E group, and difference has conspicuousness (P < 0.01)；B group RV/ (LV+OS) is lower than A, C, D
Group, difference is statistically significant (P < 0.01), and illustrating can be with to rat oral gavage Succinivibrio dextrinosolvens
RV/ (LV+OS) is effectively reduced.
The above results show with concentration as Succinivibrio dextrinosolvens 1 × 107Cfu/ml is to rat
Stomach-filling has protective effect to pulmonary hypertension, the Right ventricular hypertrophy etc. of 5500 meters of altitude environment rats of simulation once a day.Card
Bright can develop Succinivibrio fights aitiogenic drug under altitude environment at protection.
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case where shield, can be combined in any appropriate way, in order to avoid unnecessary repetition, the present invention to it is various can
No further explanation will be given for the combination of energy.
Sequence table
<110>Chinese People's Liberation Army General Hospital
<120>Succinivibrio is preventing or is treating the purposes in altitude sickness
<130> 1
<160> 2
<170> PatentIn version 3.5
<210> 1
<211> 19
<212> DNA/RNA
<213>artificial sequence (Artificial Sequence)
<400> 1
gtgccagcmg ccgcggtaa 19
<210> 2
<211> 20
<212> DNA/RNA
<213>artificial sequence (Artificial Sequence)
<400> 2
ggactachvg ggtwtctaat 20
Claims (10)
1. application of the Succinivibrio in preparation prevention or treatment plateau medicine.
2. application of the Succinivibrio according to claim 1 in preparation prevention or treatment plateau medicine, special
Sign is that the Succinivibrio includes succinovibrio dextrinosolvens (Succinivibrio dextrinosolvens).
3. according to claim 1 or 2 described in any item Succinivibrios are in preparation prevention or treatment plateau medicine
Using, which is characterized in that the altitude sickness is selected from the acute high altitude sickness generated under altitude environment and chronic plateau sickness, preferably
, the altitude environment is height above sea level 2000m or more, has low pressure, the condition of anoxic.
4. application of the Succinivibrio according to claim 3 in preparation prevention or treatment plateau medicine, special
Sign is, the acute high altitude sickness include altitude coma, plateau brain edema, plateau pneumochysis or brain, lung abnormal symptom simultaneously
Existing mixed type disease, the chronic plateau sickness include plateau heart disease, altitude erythrocytosis, high altitude hypertension,
The simultaneous mixed type disease of high altitude hypotension, plateau heart disease, polycythemia.
5. a kind of pharmaceutical composition, which is characterized in that containing Succinivibrio and pharmaceutically in the pharmaceutical composition
Acceptable auxiliary material.
6. pharmaceutical composition according to claim 5, which is characterized in that the pharmaceutically acceptable auxiliary material, which is selected from, to be carried
Body, excipient, diluent, lubricant, wetting agent, emulsifier, preservative, antioxidant, buffer, bacteriostatic agent, make preparation with
In the isotonic solute of the blood of recipient, suspending agent, suspending agent, solubilizer, thickener, stabilizer, sweetener and fragrance
A combination of one or more.
7. according to the described in any item pharmaceutical compositions of claim 5 or 6, which is characterized in that the preparation of described pharmaceutical composition
Form can be syrup, elixir, suspending agent, pulvis, granule, tablet, capsule, pastille, aqueous solution, creme, paste, washing lotion
Agent, gelling agent, emulsion.
8. a kind of food, which is characterized in that containing acceptable on the Succinivibrio and bromatology in the food
Auxiliary material.
9. food according to claim 8, which is characterized in that acceptable auxiliary material is selected from carrier, assigns in the bromatology
One of shape agent, diluent, lubricant, wetting agent, emulsifier, suspension stabiliser, preservative, sweetener and fragrance or
Two or more combinations.
10. the reagent for detecting Succinivibrio assesses the application under individual altitude environment in the product of tolerance in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910112200.9A CN109793760B (en) | 2019-02-13 | 2019-02-13 | Application of vibrio succinogenes in preparation of medicines for preventing or treating altitude diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910112200.9A CN109793760B (en) | 2019-02-13 | 2019-02-13 | Application of vibrio succinogenes in preparation of medicines for preventing or treating altitude diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109793760A true CN109793760A (en) | 2019-05-24 |
| CN109793760B CN109793760B (en) | 2022-07-19 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1910273A (en) * | 2003-11-27 | 2007-02-07 | 韩国科学技术院 | Novel rumen bacteria variants and process for preparing succinic acid employing the same |
| US20170135977A1 (en) * | 2014-07-03 | 2017-05-18 | Medical Research Council | SUCCINATE DEHYDROGENASE INHIBITORS (SDHI's) |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1910273A (en) * | 2003-11-27 | 2007-02-07 | 韩国科学技术院 | Novel rumen bacteria variants and process for preparing succinic acid employing the same |
| US20170135977A1 (en) * | 2014-07-03 | 2017-05-18 | Medical Research Council | SUCCINATE DEHYDROGENASE INHIBITORS (SDHI's) |
Non-Patent Citations (3)
| Title |
|---|
| DAOLIANG LAN等: "Correlations between gut microbiota community structures of Tibetans and geography", 《SCIENTIFIC REPORTS》 * |
| J•G霍尔德: "《简明第八版伯杰细菌鉴定手册》", 31 December 1988, 山东大学出版社 * |
| KANG LI ET.AL: "Comparative Analysis of Gut Microbiota of Native Tibetan and Han Populations Living at Different Altitudes", 《PLOS ONE》 * |
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