CN115025131B - Application of lactobacillus reuteri E9 in preparation of anxiety-relieving and sleep-improving drugs - Google Patents
Application of lactobacillus reuteri E9 in preparation of anxiety-relieving and sleep-improving drugs Download PDFInfo
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/173—Reuteri
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Abstract
The invention discloses application of lactobacillus reuteri E9 in preparation of a medicament for relieving anxiety and improving sleep, and belongs to the technical field of microorganisms. The invention discloses application of lactobacillus reuteri E9 in preparing a medicament for relieving anxiety and improving sleep, fermentation supernatant and bacterial suspension of the lactobacillus reuteri E9 can obviously reduce the movement distance, mania time and active time of zebra fish and obviously increase the resting time in an in-vivo insomnia model, and the lactobacillus reuteri E9 has the potential of being applied to relieving anxiety and improving sleep in vivo. The lactobacillus reuteri E9 disclosed by the invention has great potential application prospect in the aspects of relieving anxiety and improving sleep.
Description
Technical Field
The invention relates to the technical field of microorganisms, in particular to application of lactobacillus reuteri E9 in preparation of a medicament for relieving anxiety and improving sleep.
Background
Insomnia, including difficulty initiating or maintaining sleep, is the most common sleep disorder in the population. Over 20% of adults suffer from chronic insomnia. Many factors that lead to chronic insomnia, such as shift work, irregular work time, time differences and stress, are related to modern lifestyles. Insufficient sleep can lead to memory loss, irritability, depression, inattention and fatigue. In addition to cognitive function, sleep disorders are also associated with metabolic syndrome, such as obesity, inflammation, diabetes and cardiovascular disease. While there are many drugs available for the treatment of insomnia, including benzodiazepine receptor agonists, antihistamines, melatonin receptor agonists, anxiolytics, antidepressants and antipsychotics, the potential problems of drug dependence and abuse are alarming. Furthermore, these drugs are often associated with side effects such as dizziness, headache, somnolence, amnesia and cognitive dysfunction, even leading to an increased risk of death. It is therefore important to find a potential hypnotic agent to replace or reduce the use of these hypnotics, in a safer option to improve sleep quality and efficiency without significant adverse effects.
It was proposed by the FAO/WHO in 2002 that probiotics are defined as living microorganisms that promote host health. There is increasing evidence that long-term intake of probiotics can improve health without significant side effects. Thus, many potential functions of probiotics are proposed, even in the field of cardiac health. Microbiota-gut-brain axis (MGBA), which refers specifically to the bi-directional signaling between the gastrointestinal tract and the central nervous system through gut microorganisms, may be mediated by immunomodulation, neuroendocrine or vagal pathways. Probiotics that benefit mental or behavioral benefit through MGBA are known as mental biologicals and have a broad potential in future applications.
Studies have shown that sleep disorders lead to metabolic disorders with minor changes in intestinal microbiota. Recently, some studies have reported preliminary evidence that the intestinal microbiota affects sleep. Mice that take antibiotics for long periods of time exhibit sleep disturbances accompanied by changes in intestinal neurotransmitters. Furthermore, it was found that dietary probiotics can effectively improve stress-affected sleep conditions. These results indicate that remodelling microbiota may improve the sleep quality of the host through MGBA.
However, probiotics are currently less studied and used in alleviating anxiety and improving sleep. The probiotics strain used by domestic production enterprises depends on import for a long time, and foreign strains are not necessarily suitable for gastrointestinal tract physiological conditions of residents in China. In addition, the lack of powerful scientific research evidence of the function of probiotics seriously affects the popularization of the probiotics and products thereof. Based on the method, aiming at the function deep excavation of strain resources, the novel probiotic bacterial strain which has independent intellectual property, specific functional property and physiological property suitable for Chinese crowd is screened out, and the method is particularly important for improving the core competitiveness of Chinese probiotic production enterprises and promoting the development of Chinese probiotic products.
Therefore, providing the application of lactobacillus reuteri E9 in preparing anxiety-relieving and sleep-improving drugs is a problem to be solved urgently by those skilled in the art.
Disclosure of Invention
In view of the above, the invention provides application of lactobacillus reuteri E9 in preparing a medicament for relieving anxiety and improving sleep.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the application of the lactobacillus reuteri E9 in preparing the medicine for relieving anxiety and improving sleep, wherein the preservation number of the lactobacillus reuteri E9 is CGMCC No.21768, the lactobacillus reuteri E9 is preserved in China general microbiological culture Collection center (CGMCC), the institute of microbiological research of national academy of sciences No.3 of the national academy of sciences of China, the North-ward-Yang area of Beijing, the preservation date is 2021, 01 and 29 days, and the lactobacillus reuteri Lactobacillus reuteri is classified and named.
The lactobacillus reuteri E9 can obviously reduce the movement distance, mania time and active time of the zebra fish in a PTZ induced zebra fish insomnia model, obviously increase the rest time, and has good probiotic effects of relieving anxiety and improving sleep.
Further, the lactobacillus reuteri E9 is applied to the preparation of fermented dairy products and other foods.
Further, the lactobacillus reuteri E9 is a bacterial suspension or fermentation supernatant.
The strain capable of remarkably reducing the movement distance, mania time and active time of zebra fish and remarkably increasing the resting time in an in-vivo insomnia model comprises fermentation supernatant (extracellular secretion) and bacterial suspension (thalli) of the strain E9.
Compared with the prior art, the application of the lactobacillus reuteri E9 in preparing the medicine for relieving anxiety and improving sleep is disclosed, the lactobacillus reuteri E9 is obtained by separating and screening the excrement of long-life old people in the city and the county of the urban abaca in Guangdong, and the movement distance, mania time and active time of zebra fish can be obviously reduced and the resting time is obviously prolonged in a zebra fish insomnia model; the preparation has the potential of being applied to relieving anxiety and improving sleep in vivo, and provides theoretical reference and guiding basis for developing a probiotic preparation for relieving anxiety and improving sleep by utilizing lactobacillus reuteri E9.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only embodiments of the present invention, and that other drawings can be obtained according to the provided drawings without inventive effort for a person skilled in the art.
FIG. 1 is a drawing showing colony morphology of Lactobacillus reuteri E9 of the present invention on MRS agar plates;
FIG. 2 is a graph showing the effect of fermentation supernatant and bacterial suspension of Lactobacillus reuteri E9 on the movement track of PTZ-induced zebra fish insomnia model;
FIG. 3 is a graph showing the effect of fermentation supernatant and bacterial suspension of Lactobacillus reuteri E9 on the movement distance of PTZ-induced zebra fish insomnia model;
FIG. 4 is a graph showing the effect of fermentation supernatant, bacterial suspension of Lactobacillus reuteri E9 of the present invention on mania time in PTZ-induced zebra fish insomnia model;
FIG. 5 is a graph showing the effect of fermentation supernatant, bacterial suspension of Lactobacillus reuteri E9 of the present invention on the active time of PTZ-induced zebra fish insomnia model;
FIG. 6 is a graph showing the effect of fermentation supernatant, bacterial suspension of Lactobacillus reuteri E9 of the present invention on resting time of PTZ-induced zebra fish insomnia model.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
EXAMPLE 1 isolation, identification and preservation of Lactobacillus reuteri E9
(1) Separating: and (3) after gradient dilution, the faeces of the elder with long life are respectively inoculated into an MRS solid culture medium, a BS solid culture medium and a BHI solid culture medium for anaerobic culture at 37 ℃ for 48 hours, and single colony on a flat plate is picked for streaking separation to obtain pure colonies. Pure bacterial colony on the flat plate is inoculated in MRS liquid culture medium, anaerobic culture is carried out for 12-16 h at 37 ℃, 20% glycerol is added, and the flat plate is placed in a refrigerator at-80 ℃ for preservation.
(2) Molecular biological identification of strains: genomic DNA was extracted from the obtained strain, and a full-length fragment of 16S rDNA was amplified by PCR technique using the universal primers 27F and 1492R of 16S rDNA, followed by sequencing to identify the species of the strain.
The primer sequences of the universal primers 27F and 1492R are as follows:
27F：5’-AGAGTTTGATCCTGGCTCAG-3’；SEQ ID NO.1；
1492R：5’-GGTTACCTTGTTACGACTT-3’；SEQ ID NO.2。
experimental results: the strain screened from the faeces of the elderly in the city of the urban abaca county in Guangdong province is identified by morphological observation and 16S rDNA, wherein the strain E9 is identified as lactobacillus reuteri, and the 16S rDNA sequence is shown as SEQ ID NO. 3.
GGCTCCCTCCATAAAGGTTAGGCCACCGACTTTGGGCGTTACAAAC TCCCATGGTGTGACGGGCGGTGTGTACAAGGCCCGGGAACGTATTCAC CGCGGCATGCTGATCCGCGATTACTAGCGATTCCGACTTCGTGTAGGCG AGTTGCAGCCTACAGTCCGAACTGAGAACGGCTTTAAGAGATTAGCTT ACTCTCGCGAGCTTGCGACTCGTTGTACCGTCCATTGTAGCACGTGTGT AGCCCAGGTCATAAGGGGCATGATGATCTGACGTCGTCCCCACCTTCCT CCGGTTTGTCACCGGCAGTCTCACTAGAGTGCCCAACTTAATGCTGGCA ACTAGTAACAAGGGTTGCGCTCGTTGCGGGACTTAACCCAACATCTCAC GACACGAGCTGACGACGACCATGCACCACCTGTCATTGCGTCCCCGAA GGGAACGCCTTATCTCTAAGGTTAGCGCAAGATGTCAAGACCTGGTAA GGTTCTTCGCGTAGCTTCGAATTAAACCACATGCTCCACCGCTTGTGCG GGCCCCCGTCAATTCCTTTGAGTTTCAACCTTGCGGTCGTACTCCCCAG GCGGAGTGCTTAATGCGTTAGCTCCGGCACTGAAGGGCGGAAACCCTC CAACACCTAGCACTCATCGTTTACGGCATGGACTACCAGGGTATCTAAT CCTGTTCGCTACCCATGCTTTCGAGCCTCAGCGTCAGTTGCAGACCAGA CAGCCGCCTTCGCCACTGGTGTTCTTCCATATATCTACGCATTCCACCG CTACACATGGAGTTCCACTGTCCTCTTCTGCACTCAAGTCGCCCGGTTT CCGATGCACTTCTTCGGTTAAGCCGAAGGCTTTCACATCAGACCTAAGC AACCGCCTGCGCTCGCTTTACGCCCAATAAATCCGGATAACGCTTGCCA CCTACGTATTACCGCGGCTGCTGGCACGTAGTTAGCCGTGACTTTCTGG TTGGATACCGTCACTGCGTGAACAGTTACTCTCACGCACGTTCTTCTCC AACAACAGAGCTTTACGAGCCGAAACCCTTCTTCACTCACGCGGTGTTG CTCCATCAGGCTTGCGCCCATTGTGGAAGATTCCCTACTGCTGCCTCCC GTAGGAGTATGGACCGTGTCTCAGTTCCATTGTGGCCGATCAGTCTCTC AACTCGGCTATGCATCATCGCCTTGGTAAGCCGTTACCTTACCAACTAG CTAATGCACCGCAGGTCCATCCCAGAGTGATAGCCAAAGCCATCTTTCA AACAAAAGCCATGTGGCTTTTGTTGTTATGCGGTATTAGCATCTGTTTC CAAATGTTATCCCCCGCTCCGGGGCAGGTTACCTACGTGTTACTCACCC GTCCGCCACTCACTGGTGATCCATCGTCAATCAGGTGCAAGCACCATCA ATCAGTTGGGCCAGTGCGTACGACTGCA；SEQ ID NO.3。
The strain E9 single colony is inoculated on MRS solid culture medium, anaerobic growth is good at 37 ℃, and the colony is white, spherical, smooth in surface and neat in edge (figure 1). The strain E9 is preserved in China general microbiological culture Collection center (CGMCC), and has a preservation date of 2021, 01 and 29 days, and a classification name of Lactobacillus reuteri Lactobacillus reuteri and a preservation number of CGMCC No. 21768.
EXAMPLE 2 preparation of Lactobacillus reuteri E9 fermentation supernatant (extracellular secretion), bacterial suspension (thallus)
Lactobacillus reuteri E9 is inoculated into M after activation cultureCulturing 17. 17 h in RS liquid culture medium at 37deg.C, and adjusting concentration of fermentation bacteria to 1×10 7 Centrifuging at 4deg.C and 6000r/min for 10min to obtain culture supernatant and thallus precipitate, filtering the supernatant with 0.22 μm filter membrane to obtain fermentation supernatant (extracellular secretion); after the bacterial cell precipitate is washed twice by PBS, the bacterial cell is resuspended by PBS, and the cell concentration is regulated to be 1 multiplied by 10 7 CFU/mL gave a bacterial suspension (cell).
Example 3 effect of lactobacillus reuteri E9 on sleep, anxiety improvement in zebra fish insomnia model oxazepam and Pentatetrazolium (PTZ) were purchased from Sigma company in the united states.
Healthy wild-type AB-line zebra fish that developed to 6dpf (days post fertilization) were selected and placed in 96-well cell culture plates. The experiments set a blank control group, a model group, a positive control group and a sample (bacterial suspension and fermentation supernatant) intervention group, and each group is provided with 20 compound holes, and each hole is provided with 1 fish. Adding PBS into a blank control group, adding PBS into a model group, adding an oxazepam solution (30 mug/mL) into a positive control group, adding lactobacillus reuteri E9 bacterial suspension into a bacterial suspension group, adding lactobacillus reuteri E9 fermentation supernatant into a fermentation supernatant group, and carrying out 150 mug per hole; after incubation for 24h at 28 ℃, 50 μl of PBS was added to the blank control group, PTZ (60 mM) was added to the model group, positive control group, bacterial suspension group, and fermentation supernatant group, respectively, 20 μl of each well was incubated for 2h at 28 ℃, and then 96 well cell culture plates were placed in a zebra fish behavior analysis system (EthoVision XT 10.4, nodas information technology, inc.) for tracking, the light source was turned off to adapt the zebra fish to the environment for 5min, then behavior trace analysis software was turned on, and behavior traces of the zebra fish in the dark environment for 5min were collected. Counting the movement distance of the zebra fish; meanwhile, dividing the zebra fish into 3 motion states according to the swimming rate of the zebra fish: resting (< 4 mm/s), active (4-20 mm/s), manic (> 20 mm/s), and counting manic time, active time, resting time of zebra fish.
SPSS 19.0 software was used to statistically process the data, and experimental data were all expressed as x+ -SEM data, analyzed by one-way variance. Compared with the blank control group: ### p<0.005; compared with the model group: * P (P)<0.05， **P<0.01，***P<0.005。
The results are shown in FIGS. 2-6; as can be seen from fig. 2 and 3, the red area is the area covered by the path of the zebra fish motion; compared with a blank control group, the motion trail of the zebra fish in the model group is increased, which indicates that the activity degree of the zebra fish in the model group is increased; meanwhile, compared with a blank control group (51.52+/-5.39 cm), the movement distance (95.39 +/-4.60 cm) of the zebra fish in the model group is obviously increased (p < 0.005), which indicates that the current zebra fish insomnia model is successfully established.
Compared with the model group, the motion trail of the zebra fish in the positive control group (oxazepam) is reduced, which shows that the oxazepam can reduce the activity degree of the zebra fish in the PTZ induced zebra fish insomnia model; meanwhile, the movement distance of the zebra fish in the positive control group is 64.32 +/-2.30 cm, and the difference is obvious (P < 0.005) compared with the model group (95.39 +/-4.60 cm). Thus, oxazepam has an anxiety-relieving effect, consistent with clinical results. Compared with the model group, the motion trail of the zebra fish in the fermentation supernatant group and the bacterial suspension group of the lactobacillus reuteri E9 is reduced, which indicates that the activity degree of the zebra fish can be reduced in the PTZ induced zebra fish insomnia model by the fermentation supernatant group and the bacterial suspension group of the lactobacillus reuteri E9; meanwhile, the movement distance of zebra fish in the lactobacillus reuteri E9 fermentation supernatant group is 72.66 +/-3.23 cm and 78.72+/-3.68 cm respectively, and the average difference is obvious (P < 0.05) compared with the model group (95.39 +/-4.60 cm). Therefore, the results show that the fermentation supernatant and the bacterial suspension of the lactobacillus reuteri E9 can obviously reduce the movement distance of the zebra fish in an in-vivo insomnia model, and the effects of relieving anxiety are shown.
As can be seen from fig. 4, 5 and 6, compared with the blank control group (mania time: 15.65±0.85s, active time: 27.32±1.79s, resting time: 257.03 ±2.19 s), the mania time (62.84 ±2.85 s) and active time (72.70 ±4.58 s) of the zebra fish of the model group are both significantly increased (p < 0.005), and the resting time (164.46 ±4.90 s) is significantly decreased (p < 0.005), indicating that the current zebra fish insomnia model is successfully established.
Compared with the model group (mania time: 62.84 +/-2.85 s, activity time: 72.70 +/-4.58 s and resting time: 164.46 +/-4.90 s), the mania time (25.64+/-0.73 s) and the activity time (36.08+/-3.19 s) of the zebra fish in the positive control group are obviously reduced (p < 0.005), and the resting time (238.28 +/-3.44 s) is obviously increased (p < 0.005), so that the oxazepam has the effects of relieving anxiety and hypnotizing and is consistent with clinical results. Compared with the model group (mania time: 62.84 + -2.85 s, activity time: 72.70 + -4.58 s, resting time: 164.46 + -4.90 s), the fermentation supernatant group of lactobacillus reuteri E9, the fungus suspension group of zebra fish had a significantly reduced mania time (fermentation supernatant: 31.99+ -2.48 s, fungus suspension: 42.64 + -2.36 s), activity time (fermentation supernatant: 36.50+ -3.67 s, fungus suspension: 50.66+ -3.78 s) and resting time (fermentation supernatant: 231.51 + -4.09 s, fungus suspension: 206.70 + -4.03 s) respectively (p < 0.005). Therefore, the results show that the bacterial suspension and fermentation supernatant of the lactobacillus reuteri E9 can remarkably reduce mania time and active time of zebra fish and remarkably increase resting time in an in-vivo insomnia model, and have the effects of relieving anxiety and improving sleep.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Sequence listing
<110> Guangdong south core medical science and technology Co., ltd., guangdong Yuan lan Xin Biotechnology Co., ltd
Application of lactobacillus reuteri E9 in preparation of anxiety-relieving and sleep-improving medicines
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ggttaccttg ttacgactt 19
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ggctccctcc ataaaggtta ggccaccgac tttgggcgtt acaaactccc atggtgtgac 60
gggcggtgtg tacaaggccc gggaacgtat tcaccgcggc atgctgatcc gcgattacta 120
gcgattccga cttcgtgtag gcgagttgca gcctacagtc cgaactgaga acggctttaa 180
gagattagct tactctcgcg agcttgcgac tcgttgtacc gtccattgta gcacgtgtgt 240
agcccaggtc ataaggggca tgatgatctg acgtcgtccc caccttcctc cggtttgtca 300
ccggcagtct cactagagtg cccaacttaa tgctggcaac tagtaacaag ggttgcgctc 360
gttgcgggac ttaacccaac atctcacgac acgagctgac gacgaccatg caccacctgt 420
cattgcgtcc ccgaagggaa cgccttatct ctaaggttag cgcaagatgt caagacctgg 480
taaggttctt cgcgtagctt cgaattaaac cacatgctcc accgcttgtg cgggcccccg 540
tcaattcctt tgagtttcaa ccttgcggtc gtactcccca ggcggagtgc ttaatgcgtt 600
agctccggca ctgaagggcg gaaaccctcc aacacctagc actcatcgtt tacggcatgg 660
actaccaggg tatctaatcc tgttcgctac ccatgctttc gagcctcagc gtcagttgca 720
gaccagacag ccgccttcgc cactggtgtt cttccatata tctacgcatt ccaccgctac 780
acatggagtt ccactgtcct cttctgcact caagtcgccc ggtttccgat gcacttcttc 840
ggttaagccg aaggctttca catcagacct aagcaaccgc ctgcgctcgc tttacgccca 900
ataaatccgg ataacgcttg ccacctacgt attaccgcgg ctgctggcac gtagttagcc 960
gtgactttct ggttggatac cgtcactgcg tgaacagtta ctctcacgca cgttcttctc 1020
caacaacaga gctttacgag ccgaaaccct tcttcactca cgcggtgttg ctccatcagg 1080
cttgcgccca ttgtggaaga ttccctactg ctgcctcccg taggagtatg gaccgtgtct 1140
cagttccatt gtggccgatc agtctctcaa ctcggctatg catcatcgcc ttggtaagcc 1200
gttaccttac caactagcta atgcaccgca ggtccatccc agagtgatag ccaaagccat 1260
ctttcaaaca aaagccatgt ggcttttgtt gttatgcggt attagcatct gtttccaaat 1320
gttatccccc gctccggggc aggttaccta cgtgttactc acccgtccgc cactcactgg 1380
tgatccatcg tcaatcaggt gcaagcacca tcaatcagtt gggccagtgc gtacgactgc 1440
a 1441
Claims (4)
1. Lactobacillus reuteri @Lactobacillus reuteri) The application of E9 in preparing the medicine for relieving anxiety and improving sleep is characterized in that the preservation number of the lactobacillus reuteri E9 is CGMCC No. 21768.
2. Use of lactobacillus reuteri E9 according to claim 1 for the preparation of a medicament for alleviating anxiety and improving sleep, wherein lactobacillus reuteri E9 is a bacterial suspension or fermentation supernatant.
3. Use of lactobacillus reuteri E9 according to claim 1 for the preparation of fermented dairy products and other food products.
4. Use of lactobacillus reuteri E9 according to claim 3 for the preparation of fermented dairy products and other food products, wherein lactobacillus reuteri E9 is a bacterial suspension or a fermentation supernatant.
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| Title |
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| "Ergothioneine, a metabolite of the gut bacterium Lactobacillus reuteri, protects against stress-induced sleep disturbances";Yoshiki Matsuda 等;《Translational Psychiatry》;第10卷(第170期);第1-11页 * |
| "乳酸菌对精神性疾病作用的研究进展";骆鹏飞 等;《食品工业科技》;第38卷(第16期);第347-351页 * |
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