CN109718254B - Application of oscillatoria in preparation of drugs for preventing or treating altitude diseases - Google Patents

Application of oscillatoria in preparation of drugs for preventing or treating altitude diseases Download PDF

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CN109718254B
CN109718254B CN201910041409.0A CN201910041409A CN109718254B CN 109718254 B CN109718254 B CN 109718254B CN 201910041409 A CN201910041409 A CN 201910041409A CN 109718254 B CN109718254 B CN 109718254B
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oscillatoria
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rats
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何昆仑
冯强
赵乐
兰翔
刘继轩
赵晓静
钟琴
史文杰
杨鹏明
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Chinese PLA General Hospital
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Abstract

The invention provides application of oscillatoria in preparation of a medicament for preventing or treating altitude sickness, wherein the altitude sickness is acute altitude sickness and chronic altitude sickness which are generated in an altitude environment with an altitude of more than 2000 m.

Description

Application of oscillatoria in preparation of drugs for preventing or treating altitude diseases
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to application of oscillatoria in preparation of a medicine for preventing or treating altitude diseases.
Background
With the rise of altitude, the atmospheric pressure is reduced and the oxygen partial pressure is reduced, when an individual reaches an area with the altitude of more than 2500 m in the near term, when the individual is in an acute low-pressure and anoxic environment, if the individual cannot adapt to the environmental change, altitude reaction, namely altitude sickness, generally shows symptoms of headache, palpitation, tiredness, chest distress, shortness of breath, vomiting, anorexia, convulsion, absentmindedness of consciousness, sudden decline of cognitive ability and the like. The physical signs include accelerated heart rate, deepened respiration, slight abnormal blood pressure, edema of face or limbs, cyanosis of lips, etc. The plateau heart disease is one of the plateau diseases, and is characterized by the structural function damage of the heart caused by the low-pressure oxygen-poor environment of the plateau, namely the damage of the pulmonary hypertension and the function of the right heart. Tibetan nationality residents of the Qinghai-Tibet plateau are main population at high altitude in the world, carry out long-term physiological and genetic adaptation to the hypoxic and low-air-pressure environment of the plateau, reduce the pulmonary vasoconstriction reactivity in the hypoxic environment, and have better exercise capacity.
At present, the general medicine for preventing and treating altitude sickness is mainly acetazolamide which can rapidly improve the body adaptability, but the improvement of the habituation and the oxygen deficiency adaptation capability is always limited, the in vivo oxygen deficiency environment is not improved, the damage to the nervous system is more and more serious along with the time extension, and various neurophysiological and psychological clinical symptoms are shown.
The prior art discloses the application of medicines or related health products such as rhodiola rosea, Gaoyangning, American ginseng, Salvia miltiorrhiza pills, Baifuning and the like in preventing or treating altitude diseases, for example, patents CN103829245A, CN103948896A, CN104274808A, CN104288262A, CN104288735A, CN104288476A, CN104721202A, CN104706771A, CN105168308A, CN105193839A and the like, but the medicines or the foods have the defects of slow effect, multiple side effects and the like.
The previous research shows that the abundance of the genus oscillatoria in intestinal tracts of healthy people is remarkably higher than that of people with Crohn's disease, so that the genus oscillatoria has the potential of anti-inflammation, and the existence of the genus oscillatoria plays a crucial role in the progress of high altitude heart disease.
The human intestinal flora and metabolites thereof can enter blood circulation through intestinal mucosa, and play physiological and pathophysiological roles. Flora shifting vegetation proves to be effective in treating partial digestive system diseases. However, so far, the application of the genus oscillatoria to altitude diseases has not been reported.
Disclosure of Invention
One object of the invention is to provide the application of the genus oscillatoria in preparing products for preventing or treating altitude diseases.
In a first aspect, the present invention provides the use of genus oscillatoria for the preparation of a medicament for the prophylaxis or treatment of altitude disease.
The genus oscillatoria includes oscillatoria (Oscillibacter valerigenes).
In one embodiment of the invention, the application of the Oscillibacter valerigenes in the genus of oscillatoria in preparing medicines for preventing or treating high altitude diseases is provided.
The altitude sickness is selected from acute altitude sickness and chronic altitude sickness generated in an altitude environment.
Preferably, the plateau environment is above the altitude of 2000m and has low pressure and anoxic conditions.
Further preferably, the plateau environment is above an altitude of 2700m and has low pressure and oxygen deficiency.
In one embodiment of the present invention, the plateau environment is above 3500m in altitude, and has low pressure and oxygen-deficient conditions.
In one embodiment of the present invention, the plateau environment is above 5500m in altitude, and has low pressure and oxygen-deficient conditions.
The acute altitude disease includes but is not limited to altitude coma, altitude cerebral edema, altitude pulmonary edema or mixed diseases with abnormal symptoms of brain and lung.
The chronic altitude diseases include but are not limited to altitude heart diseases, altitude erythrocytosis, altitude hypertension, altitude hypotension, altitude heart diseases and mixed diseases with erythrocytosis.
Preferably, the altitude disease is resisting the injury of the heart, the lung and the blood vessels of the altitude disease; further preferably, the altitude sickness is a high altitude heart disease.
In an embodiment of the present invention, the high altitude heart disease includes pulmonary hypertension, right ventricular enlargement, congestive right heart failure, right ventricular hypertrophy or right heart insufficiency.
Preferably, the clinical manifestations of said altitude sickness are selected from one or a combination of more than two of headache, dizziness, palpitation, increased heart rate, fatigue, chest distress, shortness of breath, deepening respiration, nausea, vomiting, insomnia, fatigue, dim eyesight, lethargy, anorexia, convulsion, absentmindedness of consciousness, numbness of hands and feet, cyanosis of lips and fingers, edema of face, edema of limbs or a sudden decline of cognitive ability.
According to the second aspect, the invention provides a pharmaceutical composition, which contains oscillatoria and pharmaceutically acceptable auxiliary materials, and can be used for preventing or treating altitude diseases.
The genus oscillatoria includes oscillatoria (Oscillibacter valerigenes).
The pharmaceutically acceptable auxiliary materials are selected from one or the combination of more than two of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, preservatives, antioxidants, buffers, bacteriostats, solutes for making the preparation isotonic with the blood of a recipient, suspending agents, solubilizers, thickening agents, stabilizers, sweeteners and spices.
The pharmaceutically acceptable adjuvant is one or more selected from lactose, glucose, sucrose, sorbitol, mannose, starch, acacia, calcium phosphate, alginate, gelatin, calcium silicate, fine crystalline cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.
In one embodiment of the invention, the gavage concentration of the rat is 1 x 10 in the simulated plateau environment8-9×109The cfu/ml dithiacin bacterial liquid has the effect of improving pulmonary hypertension and right heart hypertrophy of rats.
The pharmaceutical composition may be formulated in the form of syrups, elixirs, suspensions, powders, granules, tablets, capsules, lozenges, aqueous solutions, creams, ointments, lotions, gels, emulsions, and the like.
The pharmaceutical preparation is preferably in unit dosage form. In this form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form may be a packaged preparation, the package containing discrete quantities of the preparation, such as tablets, capsules, and powders packaged in vials or ampoules. In addition, the unit dosage form may be a capsule, a tablet or it may be the appropriate number of any of these in a packaged form.
The amount of active ingredient in a unit dose formulation may be varied or adjusted from 0.1 mg to 1000 mg, depending on the particular application and potency of the active ingredient. The composition may also contain other suitable therapeutic agents, if desired.
Pharmaceutically acceptable carriers will depend, in part, on the particular composition being administered and on the particular method of administration of the composition. Thus, there are a variety of suitable formulations for the pharmaceutical compositions of the present invention.
Formulations suitable for parenteral administration, such as, for example, by the intravenous, intramuscular, intradermal, and subcutaneous routes, include aqueous and non-aqueous isotonic injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the recipient, and aqueous and non-aqueous suspending agents, which may contain suspending agents, solubilizing agents, thickening agents, stabilizing agents, and preservatives. In the practice of the present invention, the compositions may be administered, for example, by intravenous infusion, orally, topically, intraperitoneally, intravesically, and intrathecally. The formulations of the compounds may be presented in unit-dose or multi-dose sealed containers, such as ampules and vials. Injectable solutions and suspensions may be prepared from sterile powders, granules and tablets of the type previously described.
In the context of the present invention, the dosage administered to a subject should be sufficient to produce a beneficial therapeutic response in the subject over time. The dosage will depend upon the potency of the particular compound employed and the condition of the subject, as well as the body weight or body surface area of the subject to be treated. The size of the dose will depend upon the presence, nature and extent of any adverse side effects that accompany the administration of the particular compound in a particular subject. In determining an effective amount of a compound to be administered in the treatment or prevention of the condition being treated, a physician can assess factors such as the circulating plasma levels of the compound, the toxicity of the compound, and/or the course of the disease.
In a third aspect, the invention provides a food product comprising said genus oscillatoria and a dietetically acceptable adjuvant. The food has effect of preventing or treating altitude diseases.
The genus oscillatoria includes oscillatoria (Oscillibacter valerigenes).
The kind of the food described in the present invention is not particularly limited, and may be any known food, for example, dairy products, cookies, pastries, beverages, health products, and the like.
The food product is selected from at least one form of a solid, dairy, solution product, powder product and suspension product.
The auxiliary materials acceptable in the dietology are selected from one or the combination of more than two of carriers, excipients, diluents, lubricants, wetting agents, emulsifiers, suspension stabilizers, preservatives, sweeteners and spices.
According to an embodiment of the present invention, the dietetically acceptable auxiliary material is selected from one or a combination of two or more of lactose, glucose, sucrose, sorbitol, mannose, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium silicate, fine crystalline cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.
In a fourth aspect, the invention provides the use of an agent for detecting genus oscillatoria for the preparation of a product for assessing the tolerance of an individual in a plateau environment.
Preferably, the genus oscillatoria is in the intestinal tract.
The genus oscillatoria includes oscillatoria (Oscillibacter valerigenes).
Preferably, the reagent for detecting the oscillatoria is a reagent for detecting the abundance of the oscillatoria.
Preferably, the reagent for detecting the oscillatoria is a reagent for detecting the abundance of the oscillatoria in the intestinal tract of an individual.
In a specific embodiment of the invention, the reagent for detecting the oscillatoria is a reagent for detecting the abundance of the oscillatoria in the excrement of an individual.
Preferably, the product for evaluating the tolerance of the individual in the plateau environment comprises a reagent for detecting the abundance of oscillatoria.
Preferably, the plateau environment is above the altitude of 2000m and has low pressure and anoxic conditions.
Further preferably, the plateau environment is above an altitude of 2700m and has low pressure and oxygen deficiency.
In one embodiment of the present invention, the plateau environment is above 3500m in altitude, and has low pressure and oxygen-deficient conditions.
In one embodiment of the present invention, the plateau environment is above 5500m in altitude, and has low pressure and oxygen-deficient conditions.
The tolerance capability in the plateau environment is the susceptibility degree of the plateau disease.
Drawings
FIG. 1 is a graph showing the difference in relative abundance of Bacteroides oscillatoria in the Hanzang intestinal group in a boxplot;
FIG. 2 is a ROC curve showing the sensitivity and specificity of assessment of tolerance in plateau environments relative to abundance by Xenorhabdus;
FIG. 3 shows the administration of Oscillatoria 10 to rats7(group A), 108(group B) 109(group C), the same amount of normal saline (group D, E) is perfused, and simultaneously A, B, C, D groups of rats are raised for 28 days in a plateau environment simulating the altitude of 5500 meters, and after E groups are raised for 28 days in a normal pressure and normal oxygen environment, the change of pulmonary arterial hypertension (mPAP) of each group of rats is changed;
FIG. 4 shows the performance of Bacillus tremoreanus 10 on rats7(group A), 108(group B) 109(group C), gavage with an equal amount of physiological saline (group D, E), and while feeding A, B, C, D groups of rats in a plateau environment simulating an altitude of 5500 meters for 28 days, after feeding group E in an atmospheric normoxic environment for 28 days, the change in Right Ventricular Ejection Fraction (RVEF) and right ventricular shortening fraction (RVFS) of each group of rats:
FIG. 4a shows the RVEF variation for each group of rats;
FIG. 4b shows the RVFS variation for each group of rats;
FIG. 5 shows the performance of Bacillus tremoreanus 10 on rats7(group A), 108(group B) 109(group C), the same amount of physiological saline (group D, E) was gavaged, and simultaneously A, B, C, D groups of rats were kept in a plateau environment simulating an altitude of 5500m for 28 days, and after group E was kept in an atmospheric and normoxic environment for 28 days, the rats in each group showed RV/(LV + OS) changes.
FIG. 6 is the composition of colonies in feces of the Tibetan soldier group (Zang).
FIG. 7 colony composition in feces of Han group of soldiers (Han).
Detailed Description
Example 1 difference in intestinal bacteria abundance between people in plain areas and people in plateau areas, materials and methods:
1.1 study population
According to STROBE statement design case contrast research, taking 128 Tibetan male soldiers with habitual height above 3500m serving in a certain army in China from a certain month to a certain month in a certain year as an experimental group, and matching 128 plain Han soldiers according to the age of the Tibetan soldiers for contrast. Strictly controlling two groups of people to perform the same mixed diet of Chinese troops, keeping the same training environment and training intensity at the altitude of 3500m, and stopping smoking and drinking for 3 months. Soldiers with chronic inflammatory disease, oral antibiotics, acute infection and gastrointestinal disease were excluded.
1.2 fecal sample Collection
After each study object is brought in, each study object receives a closestool excrement collector, excrement is put into an excrement collecting pipe after the excrement is discharged, the excrement is immediately stored in a refrigerator at the temperature of minus 20 ℃, excrement specimens are transferred to a refrigerator at the temperature of minus 80 ℃ for storage the next day, and the excrement specimens are stored for later use in a unified mode.
1.3 DNA extraction
1000ul of cetyltrimethylammonium Bromide (CTAB) lysate was pipetted into a 2.0ml EP tube, lysozyme was added, approximately 500ul of the sample was added to the lysate, and the mixture was mixed several times in a 65 ℃ water bath, reversed during this period, to allow for adequate lysis of the sample. Centrifuging to obtain supernatant, adding phenol (pH8.0): chloroform: isoamyl alcohol (25: 24:1), reverse mixing, and centrifuging at 12000rpm for 10 min. Taking the supernatant, adding chloroform: isoamyl alcohol (24:1), reverse mixing, and centrifuging at 12000rpm for 10 min. The supernatant was aspirated into a 1.5mL centrifuge tube, isopropanol was added, shaken up and down, and precipitated at-20 ℃. Centrifuge at 12000rpm for 10 minutes and pour out the liquid, taking care not to pour out the pellet. The column was washed 2 times with 1ml of 75% ethanol, and the remaining small amount of liquid was collected by centrifugation again and then aspirated out with a pipette tip. And drying the clean bench or airing the clean bench at room temperature. Addition of ddH2O dissolving the DNA sample, adding RNase A1 ul to digest the RNA, and standing at 37 ℃ for 15 min. Then, the purity and concentration of the DNA are detected by agarose gel electrophoresis, an appropriate amount of sample DNA is taken out to a centrifuge tube, and the sample is diluted to 1 ng/mu l by using sterile water.
1.4 PCR amplification, mixing and purification.
Using the diluted genomic DNA as a template, specific primers with Barcode were selected according to the sequencing region 16S V3-V4:
515F:5’-GTGCCAGCMGCCGCGGTAA-3’(SEQ ID NO:1),
806R: 5 '-GGACTACHVGGGTWTCTAAT-3' (SEQ ID NO: 2), from New England Biolabs
Figure BDA0001947666230000071
High-Fidelity PCR Master Mix with GC Buffer, and High-efficiency High-Fidelity enzyme: (
Figure BDA0001947666230000072
Taq DNA Polymerase) to ensure the amplification efficiency and accuracy.
The PCR product is detected by electrophoresis by using agarose gel with 2 percent concentration; the PCR products were mixed in equal amounts according to the concentration of the PCR products, and after mixing well, the PCR products were purified by agarose gel electrophoresis using 1 XTAE 2%, and the target band was recovered by shearing. The product purification kit uses a recovery kit of GeneJET gel from Thermo Scientific company.
1.5 library construction and on-machine sequencing
Constructing a Library by using an Ion Plus Fragment Library Kit 48rxns Library construction Kit of Thermofisoher company, and using Ion S5 of Thermofisoher after the constructed Library is qualified by Qubit quantification and Library detectionTMXL was sequenced on machine.
1.6 data analysis
1.6.1 sequencing data processing
Cutadapt (V1.9.1, http:// cutapt. readthetadocs. io/en/stable /) is used for carrying out low-quality partial shearing on Reads, then each sample data is split from the obtained Reads according to Barcode, the Barcode and primer sequence are cut off for preliminary quality control to obtain original data, the Reads obtained after the treatment needs to be treated for removing a chimera sequence, the Reads sequence is compared with a species annotation database to detect the chimera sequence, and finally the chimera sequence is removed, so that the final effective data are obtained.
1.6.2 clustering of operational taxonomic unit (OUT) and species annotation
All effective data of all samples are clustered by using Upearse software (Upearse v7.0.1001, http:// www.drive5.com/Uparse /), sequences are clustered into OTUs (operational Taxonomic units) by default with 97% consistency, representative sequences of the OTUs are selected at the same time, and the sequences with the highest frequency of occurrence in the OTUs are selected as the representative sequences of the OTUs according to the algorithm principle. Species annotation is carried out on OTUS sequences, species annotation analysis is carried out by a Mothur method and an SSUrRNA database of SILVA (http:// www.arb-SILVA. de /) (the threshold value is set to be 0.8-1), taxonomic information is obtained, and the community composition of Han soldier groups and Tibetan soldier groups is counted at the genus level respectively (see figures 6 and 7).
1.6.3 calculation of relative abundance of genera and comparison of differences
Relative abundance of the genus was expressed as the oscillatoria OTU value/all the genus OTU values detected in the test samples, and the difference was compared by the Mann-Whitney test because the samples were not normally distributed. And drawing an ROC curve to evaluate the sensitivity and specificity of relative abundance of the bacteria to differential diagnosis of plateau Han population and Tibetan population, calculating a threshold value, wherein P is less than 0.05, having statistical significance, and performing statistical processing by adopting an SPSS22.0 software package.
Second, experimental results
2.1 the relative abundance differences of Oscillatoria in stool specimens of Han and Tibetan populations in plateau
Through sequencing on the intestinal oscillatoria 16sRNA of Tibetan soldiers and Han soldiers, the result is the relative abundance of the oscillatoria in Han population [ median (quartile)]Is [ 9.50X 10 ]-4(2.36×10-4,1.91×10-3)]Relative abundance of oscillatoria in plateau Tibetan population [ median (quartile)]Is [ 1.63X 10 ]-3(5.90×10-4,2.40×10-3)]The relative abundance of Han nationality population is significantly higher than Han nationality population, and is shown in FIG. 1.
2.2 assessment of sensitivity and specificity of tolerance in plateau environments by the relative abundance of Xenorhabdus
As shown in FIG. 2, the results of FIG. 2 indicate that the ROC curve shows that the relative abundance of Bacillaceae is 0.647 in AUC (area under ROC curve) value of Hanzang origin in differentially diagnosed plateau population and 1.51X 10 in relative abundance of genus-3The maximum john index of 0.358 was obtained, sensitivity and specificity were 0.768 and 0.544, respectively, accuracy was 0.699, and F1 score was 0.615.
The results show that the relative abundance of the oscillatoria in the stool specimen is detected by using 16SrRNA sequencing, so that whether the plateau population source is Tibetan or Han can be identified, or the tolerance of an individual to the plateau environment can be evaluated, and when the relative abundance of the oscillatoria is more than 1.51 multiplied by 10-3The individual can be judged to have strong tolerance to the plateau environment, and is probably the Tibetan person.
Example 2 Effect of Oscillibacter valerigenes on plateau Heart disease model rats
Test animals: SD rat purchased from Beijing Wittiulihua laboratory animals GmbH
The test method comprises the following steps:
60 male clean SD rats of about 200g are taken and fed in a low-pressure oxygen chamber, and complete nutrition feed is fed at regular time, wherein the room temperature is 22-25 ℃, and the humidity is 50-70%.
Culturing Oscillbacter valecins (LB culture medium), centrifuging 3000g, separating to obtain bacterial precipitate, and collecting 1 × 10 bacterial precipitates respectively according to determination of preliminary experiment7cfu/ml、1×108cfu/ml、1×109cfu/ml (bacteria suspended in 300uL of saline) intervened separately.
The 60 rats were randomly divided into 5 groups of 12 rats each, a group a, B, C, D and E. The rats of the A group, the B group, the C group, the D group and the E group are all raised in a normal plain environment, and the rats of each group are treated for 7 days continuously as follows:
group A rats were treated with 1X 107Gavage of cfu/ml Oscillibacter valeriigenes;
group B rats were treated with 1X 108Gavage of cfu/ml Oscillibacter valeriigenes;
group C rats were treated with 1X 109Gavage of cfu/ml Oscillibacter valeriigenes;
D. the rats in group E were injected with normal saline,
it is administered once daily. After 7 days, A, B, C, D four groups of rats are placed in a multifactor composite environment simulation medical science experiment chamber, the pressure in the chamber is adjusted to 380mmHg, plateau environment with the altitude of 5500 meters is simulated, and the experiment chamber is opened for 1 hour every day so as to add feed and water to animals, and simultaneously, the environment 12 of the rats is kept: 12 hours alternating day and night for 28 days. Group E rats were housed in the same room under atmospheric and normoxic conditions.
The rats were anesthetized with 3% pentobarbital sodium, 0.2ml/100g by intraperitoneal injection, and the Right Ventricular Ejection Fraction (RVEF) and the right ventricular foreshortening fraction (RVFS) were measured by ultrasonic examination. The rat was then fixed in supine position on an operating table, tracheostomized, connected to a ventilator, opened chest, heart exposed, catheterized into the right ventricle, right heart catheterized, and mean pulmonary arterial pressure (mPAP) measured. The rats were sacrificed, the hearts were removed, the atrial tissue and the attached fat were removed, the left and right ventricles were separated, the filter paper was blotted with water, and weighed, respectively, and the right ventricular specific gravity RV/(LV + OS) was measured.
All data are expressed by x +/-s, the comparison among groups is carried out by one-factor variance analysis, the difference is shown as P < 0.05, the statistical significance is achieved, and the SPSS22.0 software package is adopted for statistical processing.
Test results
1. Effect of bacterial liquid on rat mPA
After the rats are fed in the low-pressure hypoxic environment for 28 days, the mPAP of the rats is obviously increased, and the difference is significant (P < 0.01), which indicates that the low-pressure hypoxic environment can cause the failure of the right heart of the normal rats. However, in the low-pressure hypoxic environment, compared with the normal group E, namely the normal rats, the mPAP of the B, C group rats is obviously lower than that of the group D, the group B is lower than that of the group C, but the difference is not obvious in statistics, and as shown in figure 3, the fact that the Oscillbacter valigens perfused into the rats can effectively reduce the mPAP generated by the plateau environment is demonstrated.
2. Effect of bacterial liquid on rat RVEF and RVFS
The variation of RVEF and RVFS for each group of rats 28 days after the rats are fed in a hypoxic environment under low pressure is shown in figure 4, the variation of RVEF for each group of rats is shown in figure 4a, and the variation of RVFS for each group of rats is shown in figure 4 b. As shown by the data in the figure, there was no significant difference in RVEF and RVFS for the rats in group B compared to the normal group E, i.e., normal rats, and the RVEF and RVFS for the rats in group A, C, D were significantly lower than those in group B, E with significant difference (P < 0.05), while the RVEF and RVFS for the rats in group C were higher than those in group A, indicating a ratio of 1X 108-1×109The gastric lavage of cfu/ml oscillobacter valeriigenes has therapeutic effect on structural function damage of heart caused by plateau low-pressure oxygen-deficient environment, especially 1 × 108cfu/ml Oscillibacter valerigens have better therapeutic effect.
3. Effect of bacterial liquid on RV/(LV + OS) of rat
FIG. 5 shows the RV/(LV + OS) change of rats in each group after 28 days of low-pressure and low-oxygen feeding, and the RV/(LV + OS) of the rats in A, B, C, D group is obviously increased compared with that in E group, and the difference is significant (P < 0.01); group B RV/(LV + OS) was lower than group A, C, D, the difference was statistically significant (P < 0.01), indicating that Oscillbacter valerigenes can effectively reduce RV/(LV + OS) when rats were gavaged.
The above results show that the concentration is 1X 10 for oscillobacter valericins8The cfu/ml is used for intragastric administration to rats once a day, and has protective effects on pulmonary hypertension, right heart hypertrophy and the like of rats simulating 5500m plateau environment. It was demonstrated that oscillatoria can be developed into drugs that protect against the response in the plateau environment.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
Sequence listing
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Claims (2)

1. The application of the genus oscillatoria in preparing the medicines for preventing or treating the high altitude diseases is characterized in that the genus oscillatoria is oscillatoria (Oscillibacter valerigenes), and the high altitude diseases are the high altitude heart diseases.
2. The use of the genus oscillatoria according to claim 1 for the preparation of a medicament for the prevention or treatment of altitude sickness, wherein the altitude environment is above 2000m, with low pressure and anoxic conditions.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103829245A (en) * 2014-03-13 2014-06-04 太原纠偏食品开发有限公司 Rectification food for down regulating altitude stress and preparation method of rectification food
CN104274808A (en) * 2014-10-11 2015-01-14 中山百鸥医药科技有限公司 Traditional Chinese medicine composition for anti-altitude stress
US20160232280A1 (en) * 2014-10-21 2016-08-11 uBiome, Inc. Method and system for microbiome-derived characterization, diagnostics and therapeutics for cardiovascular disease conditions

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103829245A (en) * 2014-03-13 2014-06-04 太原纠偏食品开发有限公司 Rectification food for down regulating altitude stress and preparation method of rectification food
CN104274808A (en) * 2014-10-11 2015-01-14 中山百鸥医药科技有限公司 Traditional Chinese medicine composition for anti-altitude stress
US20160232280A1 (en) * 2014-10-21 2016-08-11 uBiome, Inc. Method and system for microbiome-derived characterization, diagnostics and therapeutics for cardiovascular disease conditions

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Metagenomic and metabolomic analyses unveil dysbiosis of gut;Xiao Cui等;《Scientific Report》;20080112;第8卷(第635期);第498-506页 *
汪冬等.高原缺氧环境下肠道菌群紊乱与急性重症高原病.《胃肠病学和肝病学杂志》.2017,第26卷(第2期),222-226. *
高原缺氧环境下肠道菌群紊乱与急性重症高原病;汪冬等;《胃肠病学和肝病学杂志》;20170228;第26卷(第2期);222-226 *

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