CN111548964B - 一种干酪乳杆菌及其在防治肾炎中的应用 - Google Patents
一种干酪乳杆菌及其在防治肾炎中的应用 Download PDFInfo
- Publication number
- CN111548964B CN111548964B CN202010424358.2A CN202010424358A CN111548964B CN 111548964 B CN111548964 B CN 111548964B CN 202010424358 A CN202010424358 A CN 202010424358A CN 111548964 B CN111548964 B CN 111548964B
- Authority
- CN
- China
- Prior art keywords
- lactobacillus casei
- kidney
- application
- lactobacillus
- renal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 244000199866 Lactobacillus casei Species 0.000 title claims abstract description 26
- 235000013958 Lactobacillus casei Nutrition 0.000 title claims abstract description 26
- 229940017800 lactobacillus casei Drugs 0.000 title claims abstract description 26
- 201000008383 nephritis Diseases 0.000 title abstract description 8
- 239000006041 probiotic Substances 0.000 claims abstract description 33
- 235000018291 probiotics Nutrition 0.000 claims abstract description 33
- 230000000529 probiotic effect Effects 0.000 claims abstract description 26
- 241000020630 Lactobacillus casei Lc-10 Species 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000004321 preservation Methods 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 235000021001 fermented dairy product Nutrition 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 238000009098 adjuvant therapy Methods 0.000 claims description 2
- 235000013361 beverage Nutrition 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 17
- 210000003734 kidney Anatomy 0.000 abstract description 16
- 239000003833 bile salt Substances 0.000 abstract description 12
- 206010063897 Renal ischaemia Diseases 0.000 abstract description 11
- 206010016654 Fibrosis Diseases 0.000 abstract description 10
- 230000004761 fibrosis Effects 0.000 abstract description 9
- 230000001681 protective effect Effects 0.000 abstract description 9
- 239000002253 acid Substances 0.000 abstract description 8
- 230000010412 perfusion Effects 0.000 abstract description 8
- 230000001154 acute effect Effects 0.000 abstract description 6
- 208000037976 chronic inflammation Diseases 0.000 abstract description 6
- 230000006020 chronic inflammation Effects 0.000 abstract description 6
- 230000000968 intestinal effect Effects 0.000 abstract description 6
- 230000008439 repair process Effects 0.000 abstract description 6
- 230000006378 damage Effects 0.000 abstract description 5
- 238000002474 experimental method Methods 0.000 abstract description 5
- 230000003907 kidney function Effects 0.000 abstract description 5
- 210000005239 tubule Anatomy 0.000 abstract description 5
- 208000027418 Wounds and injury Diseases 0.000 abstract description 4
- 230000006907 apoptotic process Effects 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 4
- 208000014674 injury Diseases 0.000 abstract description 4
- 230000008929 regeneration Effects 0.000 abstract description 4
- 238000011069 regeneration method Methods 0.000 abstract description 4
- 230000007881 chronic fibrosis Effects 0.000 abstract description 3
- 208000028867 ischemia Diseases 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 230000015784 hyperosmotic salinity response Effects 0.000 abstract description 2
- 230000002757 inflammatory effect Effects 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 230000028327 secretion Effects 0.000 abstract description 2
- 230000035899 viability Effects 0.000 abstract description 2
- 210000003292 kidney cell Anatomy 0.000 abstract 1
- 239000001963 growth medium Substances 0.000 description 20
- 241000894006 Bacteria Species 0.000 description 19
- 241000186660 Lactobacillus Species 0.000 description 19
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 18
- 229940039696 lactobacillus Drugs 0.000 description 18
- 235000013336 milk Nutrition 0.000 description 15
- 239000008267 milk Substances 0.000 description 15
- 210000004080 milk Anatomy 0.000 description 15
- 230000001580 bacterial effect Effects 0.000 description 10
- 238000012258 culturing Methods 0.000 description 10
- 210000004051 gastric juice Anatomy 0.000 description 10
- 206010063837 Reperfusion injury Diseases 0.000 description 9
- 235000014655 lactic acid Nutrition 0.000 description 9
- 239000004310 lactic acid Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 229940093761 bile salts Drugs 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 229920001817 Agar Polymers 0.000 description 7
- 239000008272 agar Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000009630 liquid culture Methods 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 235000013618 yogurt Nutrition 0.000 description 4
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 3
- 206010061481 Renal injury Diseases 0.000 description 3
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 3
- 229940099352 cholate Drugs 0.000 description 3
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
- 208000037806 kidney injury Diseases 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 210000005084 renal tissue Anatomy 0.000 description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 102000016938 Catalase Human genes 0.000 description 2
- 108010053835 Catalase Proteins 0.000 description 2
- 108010078777 Colistin Proteins 0.000 description 2
- 206010023421 Kidney fibrosis Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 229960001127 colistin sulfate Drugs 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000008944 intestinal immunity Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 238000009629 microbiological culture Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- ZESIAEVDVPWEKB-ORCFLVBFSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O ZESIAEVDVPWEKB-ORCFLVBFSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 1
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
- 101710185991 Hepatitis A virus cellular receptor 1 homolog Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 210000004322 M2 macrophage Anatomy 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000018967 Platelet-Derived Growth Factor beta Receptor Human genes 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 101710164680 Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000003690 classically activated macrophage Anatomy 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000009212 extracorporeal shock wave lithotripsy Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
- A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/385—Concentrates of non-alcoholic beverages
- A23L2/39—Dry compositions
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/125—Casei
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
- C12R2001/245—Lactobacillus casei
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Nutrition Science (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本申请公开了一株干酪乳杆菌及其在防治肾炎中的应用。本申请经体外耐酸性试验和胆盐耐受性试验筛选出在肠道环境中生存能力较强的潜在益生菌干酪乳杆菌，并通过动物实验证实了其对急性肾缺血灌注损伤具有保护作用，减少炎症因子的分泌和纤维化程度；减缓肾脏慢性炎症的进程；促进肾小管的再生修复；减少肾缺血灌注慢性纤维化引起的肾脏细胞凋亡，对肾脏功能具有保护作用。
Description
技术领域
本申请涉及生物技术领域，特别涉及一种干酪乳杆菌及其在防治肾炎中的应用。
背景技术
肾炎是一种免疫性疾病是肾免疫介导的炎性反应，是不同的抗原微生物感染人体后，产生不同的抗体，结合成不同的免疫复合物，中国科学院肾病检测研究所认为沉积在肾脏的不同部位造成的病理损伤，形成不同的肾炎类型。肾炎是肾脏疾病中最常见的一种，其症状表现为乏力、腰部疼痛、肉眼血尿、水肿、高血压、肾功能异常及尿量减少等等。同时，在肾脏手术、肾移植和体外震波碎石等过程中，均可发生不同程度的再灌注损伤，它是急性肾衰最常见的原因。肾脏由于其血流高灌注的特性，缺血再灌注损伤发生率较高。
乳酸菌(Lactic acid bacteria，LAB)是一群革兰氏阳性、能发酵糖类产乳酸的细菌总称，其在自然界中广泛存在。其中的乳杆菌与人类生活关系密切，广泛应用于食品发酵，工业乳酸发酵及医疗保健领域中的有益微生物之一。乳杆菌是最重要的益生菌菌属，表现出极强的益生特性，如耐胃肠道消化液和胆盐，在胃肠液中定殖生长等等。同时，益生菌的干预可以增加肠道菌群中有益菌的含量，抗炎细菌的比例，提高机体免疫力。目前尚未发现对减缓肾脏慢性炎症的进程，促进肾脏损伤的修复，对肾脏功能具有保护作用的乳酸菌。
发明内容
本申请的目的之一在于提供一株干酪乳杆菌LC-10(Lactobacillus casei LC-10)。
本申请的目的之二在于提供干酪乳杆菌LC-10(Lactobacillus casei LC-10)在预防和辅助治疗肾脏炎症中的应用。
本申请的目的之三在于提供干酪乳杆菌LC-10在制备直投式发酵剂、发酵乳制品和益生菌固体饮料、片剂的功能性保健品中的应用。
本申请的目的是通过如下技术方案实现的：
本申请所述的干酪乳杆菌(Lactobacillus casei LC-10)分离自锡林郭勒大草原自然发酵的酸马奶，具体地，是通过如下方法分离筛选得到的：
1.样品中的乳杆菌分离于自然发酵的酸马奶，分别吸取2mL所述酸马奶于灭菌小试管中并封口，1mL于装有灭菌CaCO3粉的无菌采样瓶中(容积为2mL)，拧紧螺旋帽作为备用样品保藏在4℃冰箱内，尽快将乳酸菌进行分离；
2.将乳杆菌分离时，吸取1mL酸马奶样品接种于10mL灭菌石蕊牛乳培养基中，置于30-37℃恒温箱内增菌培养至酸化凝固，在培养基颜色变为粉红时将其取出，用灭菌接种环划线接种于含有10ppm放线菌酮和10ppm硫酸粘菌素的BL琼脂培养基上；
3.放入
gaspak厌氧培养罐中，置于30-37℃条件下，培养48～72h。待菌落形成后，用接种环或接种针挑取菌落，接种于TPY液体中，置于30-37℃条件下，培养24～48h；
4.待菌株生长良好后，再次划线接种于BL琼脂培养基中培养(培养温度和时间同上)，仔细观察记录菌落形态和革兰氏染色细胞形态特征，并同时进行过氧化氢酶试验；
5.将所述乳杆菌进一步纯化培养，并采用低温真空冷冻保存；将从酸马奶样品中分离的乳杆菌菌株，经分析鉴定后的制成供试菌液，吸取菌悬液10μL接种于5mL pH值为3.5的MRS液体培养基，置于37℃培养24h；同时吸取菌悬液1.0mL与9.0mL pH值为3.0的人工胃液。其中，人工胃液制备法：NaCl0.2％、胃蛋白酶(pepsin，sigma)0.35％，用1mol/L HCl调整pH值为3.0后，过滤除菌备用。混合后，于37℃培养，分别在开始时间0h和3h后取样，使用BCP琼脂培养基测定活菌数并计算菌株存活率；
6.通过以上方法筛选出具有高耐酸性生长和耐胃酸的乳杆菌菌株，并进一步测定其在不同人工胃液和肠液中的存活能力以及通过体外耐胆盐试验和降低胆固醇试验，由此获得干酪乳杆菌。
本申请将该菌株提交专利认可的机构进行保藏，其微生物保藏编号为：CGMCCNo.17343；分类命名为：干酪乳杆菌(Lactobacillus casei)；保藏单位：中国微生物菌种保藏管理委员会普通微生物中心；保藏时间：2019年3月18日，保藏地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所；该菌株的检测结果为存活。
乳杆菌的鉴定：分离纯化的乳杆菌(Lactobacillus casei LC-10)，经生理生化学特性分析和16SrDNA序列分析的方法鉴定，其微生物学特性如表1所示。
表1 Lactobacillus casei LC-10的生物学特性
与现有技术相比，本申请提供的干酪乳杆菌(Lactobacillus casei LC-10)以及与之相关的技术方案具有如下有益效果：
本申请中经体外耐酸性试验和胆盐耐受性试验筛选出在肠道环境中生存能力较强的潜在益生菌干酪乳杆菌(Lactobacillus casei LC-10)，并通过动物实验证实了其对急性肾缺血灌注损伤具有保护作用，减少炎症因子的分泌和纤维化程度；减缓肾脏慢性炎症的进程；促进肾小管的再生修复；减少肾缺血灌注慢性纤维化引起的肾脏细胞凋亡，对肾脏功能具有保护作用。
附图说明
为了更清楚地说明本申请实施例或现有技术中的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本申请乳酸菌的分离、纯化及保存操作流程图；
图2为Lactobacillus casei LC-10改善肾脏缺血再灌注损伤实验设计图；
图3为小鼠肾脏观察结果；
图4为小鼠左肾的肾脏系数柱形图；
图5为小鼠右肾的肾脏系数柱形图；
图6为小鼠尿素氮的柱形图；
图7为小鼠肌酐的柱形图；
图8为PAS染色检测肾脏肾小管细胞损伤结果；
图9为F4/80mRNA表达定量结果；
图10为VEGF-A mRNA表达定量结果；
图11为肾组织免疫荧光染色结果；
图12为肾脏组织细胞增殖再生分子Ki67表达结果；
图13为Masson及天狼新红染色结果；
图14为纤维化标记蛋白α-SMA在急性模型中mRNA表达量柱形图；
图15为纤维化标记物ICAM-1在急性模型中mRNA表达量柱形图；
图16为TGF-β1在慢性模型中mRNA表达量柱形图；
图17为纤维化标记物ICAM-1在慢性模型中mRNA表达量柱形图；
图18为肾脏纤维化蛋白水平结果。
具体实施方式
本申请提供一株干酪乳杆菌LC-10(Lactobacillus casei LC-10)，所述干酪乳杆菌(Lactobacillus casei LC-10)采集分离于中国内蒙古锡林郭勒盟正蓝旗自然发酵的酸马奶中，是一株具有良好的胃肠液和胆盐耐受性的益生菌菌株；该菌株已保藏于中国微生物菌种保藏管理委员会普通微生物中心，保藏号：CGMCC No.17343；分类命名为：干酪乳杆菌(Lactobacillus casei)；保藏时间：2019年3月18日，保藏地址：北京市朝阳区北辰西路1号院3号，中国科学院微生物研究所；该菌株的检测结果为存活。
实施例1样品中乳杆菌的分离与纯化
样品中干酪乳杆菌分离与纯化过程参见图1。
1.样品中的乳杆菌分离于自然发酵的酸马奶，分别吸取2mL所述酸马奶于灭菌小试管中并封口，1mL于装有灭菌CaCO3粉的无菌采样瓶中(容积为2mL)，拧紧螺旋帽作为备用样品保藏在4℃冰箱内，尽快将乳酸菌进行分离；
2.将乳杆菌分离时，吸取1mL酸马奶样品接种于10mL灭菌石蕊牛乳培养基中，置于30-37℃恒温箱内增菌培养至酸化凝固，在培养基颜色变为粉红时将其取出，用灭菌接种环划线接种于含有10ppm放线菌酮和10ppm硫酸粘菌素的BL琼脂培养基上；
3.放入
gaspak厌氧培养罐中，置于30-37℃条件下，培养48～72h。待菌落形成后，用接种环或接种针挑取菌落，接种于TPY液体中，置于30-37℃条件下，培养24～48h；
4.待菌株生长良好后，再次划线接种于BL琼脂培养基中培养(培养温度和时间同上)，仔细观察记录菌落形态和革兰氏染色细胞形态特征，并同时进行过氧化氢酶试验；
5.将所述乳杆菌进一步纯化培养，并采用低温真空冷冻保存；将从酸马奶样品中分离的乳杆菌菌株，经分析鉴定后的制成供试菌液，吸取菌悬液10μL接种于5mL pH值为3.5的MRS液体培养基，置于37℃培养24h；同时吸取菌悬液1.0mL与9.0mL pH值为3.0的人工胃液。其中，人工胃液制备法：NaCl0.2％、胃蛋白酶(pepsin，sigma)0.35％，用1mol/L HCl调整pH值为3.0后，过滤除菌备用。混合后，于37℃培养，分别在开始时间0h和3h后取样，使用BCP琼脂培养基测定活菌数并计算菌株存活率；
6.通过以上方法筛选出具有高耐酸性生长和耐胃酸的乳杆菌菌株，并进一步测定其在不同人工胃液和肠液中的存活能力以及通过体外耐胆盐试验和降低胆固醇试验，由此获得干酪乳杆菌。
实施例2干酪乳杆菌(Lactobacillus casei LC-10)的鉴定
分离纯化的干酪乳杆菌(Lactobacillus casei LC-10)，经生理生化学特性分析和16SrDNA序列分析的方法鉴定，其微生物学特性如表1所示。
表1 Lactobacillus casei LC-10的生物学特性
实施例3干酪乳杆菌(Lactobacillus casei LC-10)的耐酸性及其人工胃肠液中 的耐受性分析。
从酸马奶样品中分离鉴定的50株乳杆菌中，经过pH值为3.5的MRS液体培养基中生长试验及在pH值为3.0的人工胃液中的存活率测定，筛选得到1株耐酸性极强的乳杆菌，即干酪乳杆菌(Lactobacillus casei LC-10)。
Lactobacillus casei LC-10菌株经过pH值为3.5的MRS液体培养基中生长试验及在pH值为3.0的人工胃液中的存活率测定，结果见表2。
表2 Lactobacillus casei LC-10在pH3.5及pH3.0人工胃液中生长情况
注：表中菌数均为两次实验的平均值。
结果显示，本申请的干酪乳杆菌(Lactobacillus casei LC-10)具有较强的耐性和耐酸生长特性、能够耐受人工胃肠消化液，尤其在脱脂乳液中能够耐受pH值为2.0的人工胃液。
实施例4干酪乳杆菌(Lactobacillus caseiLC-10)对胆盐的耐受性分析
将本申请的Lactobacillus casei LC-10接种于含有0.3％胆盐的培养基中，厌氧培养观察分析了胆盐对其生长的影响，结果如表3所示。
表3 Lactobacillus casei LC-10对胆盐的耐受性(n＝3，x±sd)
将本申请的Lactobacillus casei LC-10接种于含不同浓度胆盐的TPY琼脂和液体培养基中，通过对其生长情况的观察，分析了能够耐受胆盐的最高浓度，结果如表4所示：Lactobacillus casei LC-10耐受的最高胆盐浓度达1.8％。
表4 Lactobacillus casei LC-10对不同浓度胆盐的耐受性
注：ΔA620为0h和12h吸光值之差，结果为三次实验的平均值，+表示有菌落生长，-表示无菌落生长，ND为测试。
由于本申请的干酪乳杆菌(Lactobacillus casei LC-10)的这种特性，所述干酪乳杆菌作为益生菌能够抵御消化道环境的不利影响并在肠道内很好的黏附和定植。益生菌的干预可以增加肠道菌群中有益菌的含量，抗炎细菌的比例，提高机体免疫力。肠道免疫力的调节进一步影响毒素的生成，减缓肾脏慢性炎症的进程，促进肾脏损伤的修复，对肾脏功能具有保护作用。随着人们对乳酸菌代谢和遗传特性的深入了解以及对其机理的认识，已经广泛接受了乳酸菌这类保健制品。另外，口服是益生菌进入肠道的主要途径，益生菌只有在经受胃酸和小肠中高浓度胆盐影响的情况下成活率高的菌株，才可发挥作用；同时，产品中稳定的活菌数或者微生态制剂中活菌的数量是其发挥作用的关键，所以，活菌制剂的应用要求单位产品达到一定的活菌数，以符合有效治疗剂量标准。
因此，该菌株适用于功能性发酵乳制品的生产、也可作为功能性食品添加剂或保健制剂应用于调节免疫功能的各个方面。
实验例1 Lactobacillus casei LC-10改善肾脏缺血再灌注损伤
选用雄性小鼠分三组，见表5。
表5 Lactobacillus casei LC-10改善肾脏缺血再灌注损伤实验设计内容
造模采用双侧肾动脉夹闭缺血30min，Sham组仅切开腹腔，游离两侧肾蒂，但不阻断任何动脉，实验设计见图2；将本申请的Lactobacillus casei LC-10制备成2.0×109CFU/g的微生态制剂，用量为2x109 CFU/d/只进行喂食。
缺血再灌注损伤后5d(早期)，肾脏体积稍增大，益生菌组没有模型组增大明显。缺血再灌注损伤后28d(晚期)，肾脏体积缩小，模型组缩小较益生菌组明显，参见图3至图5；益生菌组、模型组肌酐及尿素氮均高于对照组，模型组肌酐及尿素氮明显高于益生菌组，参见图6和图7。说明益生菌LC-10可以缓解缺血灌注带来的急性肾损伤。
PAS染色检测肾脏肾小管细胞损伤(包括扩张、坏死、管型等)，Sham、益生菌组明显低于模型组；Sham、益生菌组肾脏损伤因子KIM-1明显少于模型组；Sham、益生菌组LTL染色近端小管刷状缘面积与模型组比较增多，见图8。进一步表明L.casei LC-10对急性肾缺血灌注损伤的保护作用。
肾脏组织巨噬细胞标记物F4/80在益生菌组较I/R组明显减少；益生菌组血管生成因子VEGF-A较模型组也明显增加，参见图9和图10。表明益生菌干预可以减缓肾脏慢性炎症的进程。益生菌组较模型组相比M2型巨噬细胞增多，M1型巨噬细胞减少，参见图11。表明益生菌通过调节M1和M2巨噬细胞的平衡改善慢性炎症的形成。
模型组早期大部分细胞增殖位于间质内，晚期间质仍可见部分细胞增殖，表明模型组的增殖细胞主要作用可能是诱导炎性或纤维化；益生菌组早期大部分细胞增殖位于肾小管上，晚期肾小管上仍可见增殖细胞，见图12。表明益生菌干预主要可能作用于促进了肾小管的再生修复。
Masson及天狼新红染色显示小鼠肾脏缺血再灌注损伤28d后已出现纤维化，见图13；益生菌组纤维化程度明显低于模型组，纤维化标记物ICAM-1在急性和慢性模型中均显著降低，见图15和图17。进一步表明益生菌对肾缺血灌注损伤具有保护作用。
益生菌组肾脏纤维化标记蛋白α-SMA水平明显低于模型组，见图14。同时β型血小板源性生长因子受体PDGFRβ和凋亡基因Bax表达在慢性模型中均显著降低，见图16和图18，表明益生菌可以减少肾缺血灌注慢性纤维化引起的肾脏细胞凋亡，对肾脏功能具有保护作用。
综上所述，益生菌LC-10改善肾脏缺血再灌注损伤可能的机理是通过调节肠道免疫，减少毒素的生成、巨噬细胞浸润，抑制炎症反应及氧化应激并促进小管修复，减轻纤维化。
本领域技术人员在考虑说明书及实践这里公开的申请后，将容易想到本申请的其它实施方案。本申请旨在涵盖本申请的任何变型、用途或者适应性变化，这些变型、用途或者适应性变化遵循本申请的一般性原理并包括本申请未公开的本技术领域中的公知常识或惯用技术手段。说明书和实施例仅被视为示例性的，本申请的真正范围和精神由下面的权利要求指出。
应当理解的是，本申请并不局限于上面已经描述并在附图中示出的精确结构，并且可以在不脱离其范围进行各种修改和改变。本申请的范围仅由所附的权利要求来限制。
Claims (3)
1.一株干酪乳杆菌(Lactobacillus casei)LC-10，其特征在于，其微生物保藏编号为：CGMCC No.17343。
2.权利要求1所述的干酪乳杆菌LC-10在制备预防和辅助治疗肾脏炎症药物中的应用。
3.权利要求1所述的干酪乳杆菌LC-10在制备直投式发酵剂、发酵乳制品和益生菌固体饮料、片剂型功能性保健品中应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010424358.2A CN111548964B (zh) | 2020-05-19 | 2020-05-19 | 一种干酪乳杆菌及其在防治肾炎中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010424358.2A CN111548964B (zh) | 2020-05-19 | 2020-05-19 | 一种干酪乳杆菌及其在防治肾炎中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111548964A CN111548964A (zh) | 2020-08-18 |
| CN111548964B true CN111548964B (zh) | 2022-08-26 |
Family
ID=72006530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010424358.2A Active CN111548964B (zh) | 2020-05-19 | 2020-05-19 | 一种干酪乳杆菌及其在防治肾炎中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111548964B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114686402B (zh) * | 2022-04-25 | 2023-06-20 | 善恩康生物科技（苏州）有限公司 | 乳酸乳球菌乳酸亚种hfy14及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101338283A (zh) * | 2007-07-06 | 2009-01-07 | 内蒙古农业大学 | 一种干酪乳杆菌及其在固态发酵中的应用 |
| CN102373173A (zh) * | 2011-11-11 | 2012-03-14 | 石家庄君乐宝乳业有限公司 | 干酪乳杆菌n1115、其免疫调节作用及应用 |
| CN109674827A (zh) * | 2019-02-11 | 2019-04-26 | 华中科技大学同济医学院附属同济医院 | 干酪乳杆菌Zhang在改善急性肾损伤，防治肾间质纤维化中的应用 |
-
2020
- 2020-05-19 CN CN202010424358.2A patent/CN111548964B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101338283A (zh) * | 2007-07-06 | 2009-01-07 | 内蒙古农业大学 | 一种干酪乳杆菌及其在固态发酵中的应用 |
| CN102373173A (zh) * | 2011-11-11 | 2012-03-14 | 石家庄君乐宝乳业有限公司 | 干酪乳杆菌n1115、其免疫调节作用及应用 |
| CN109674827A (zh) * | 2019-02-11 | 2019-04-26 | 华中科技大学同济医学院附属同济医院 | 干酪乳杆菌Zhang在改善急性肾损伤，防治肾间质纤维化中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| Lactobacillus casei Zhang Prevents Jejunal Epithelial Damage to Early-Weaned Piglets Induced by Escherichia coli K88 via Regulation of Intestinal Mucosal Integrity, Tight Junction Proteins and Immune Factor Expression;Yuying Wang等;《J Microbiol Biotechnol》;20190628;第29卷(第6期);863-876 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111548964A (zh) | 2020-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111484957B (zh) | 动物双歧杆菌乳亚种i797、其分离纯化方法及应用 | |
| CN110106119B (zh) | 一株分离自母乳的鼠李糖乳杆菌m9及其应用 | |
| CN108486000B (zh) | 一种双歧杆菌单菌发酵乳制备方法及其应用 | |
| CN110577912B (zh) | 一种格氏乳杆菌及其在制备发酵乳中的应用 | |
| CN112143680B (zh) | 具有抗氧化功效副干酪乳杆菌zjuids05及其应用 | |
| CN111575207B (zh) | 一株分离自酸牦牛奶的副干酪乳杆菌及其应用 | |
| CN107164263A (zh) | 一种可调节肠道功能、预防结肠炎的发酵乳杆菌hy01及其用途 | |
| CN104531549B (zh) | 一种可调节肠道运动、预防便秘的发酵乳杆菌Lactobacillus fermentum strain Zhao及其用途 | |
| CN101139557A (zh) | 一种干酪乳杆菌及其在改善血脂代谢和免疫调节中的应用 | |
| CN112625979B (zh) | 一种对抗幽门螺杆菌的干酪乳杆菌及其应用 | |
| CN114085792B (zh) | 一种用于防治结肠癌的副干酪乳杆菌及其应用 | |
| CN104430847A (zh) | 发酵乳杆菌Lactobacillus fermentum Lee工作发酵剂制品及其预防便秘保健用途 | |
| CN107227275A (zh) | 一种发酵乳杆菌hy01及其用途 | |
| CN113755409B (zh) | 一种缓解胰岛素抵抗的长双歧杆菌及其应用 | |
| CN104381440A (zh) | 发酵乳杆菌Lactobacillus fermentum Lee工作发酵剂制品及其预防便秘保健用途 | |
| CN116024130A (zh) | 一株降血尿酸发酵乳杆菌a21215及其应用 | |
| CN114437989B (zh) | 一种具有降血糖作用的发酵乳杆菌lf028及其应用 | |
| CN111548964B (zh) | 一种干酪乳杆菌及其在防治肾炎中的应用 | |
| CN117106672B (zh) | 一种改善衰老相关的认知障碍的短双歧杆菌及其应用 | |
| CN108018248B (zh) | 一种具有调节抗生素引起的菌群结构紊乱的干酪乳杆菌 | |
| Pato et al. | Hypocholesterolemic effect of indigenous dadih lactic acid bacteria by deconjugation of bile salts | |
| CN116396890B (zh) | 用于防治结肠癌的植物乳杆菌zjuids15及其应用 | |
| CN115895966B (zh) | 一株辅助缓解痛风的两歧双歧杆菌bl002及其应用 | |
| CN109362882B (zh) | 发酵乳杆菌cqpc07及其在制备食品或改善溃疡性结肠炎的药品中的应用 | |
| CN116445360A (zh) | 一株具有缓解慢性酒精性肝损伤功效的鼠李糖乳酪杆菌及其应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Xiaojun Inventor after: Zhang Lingyu Inventor after: Ma Jie Inventor after: Zhang Jianjun Inventor after: Qimugesudu Inventor after: Yang Huijuan Inventor before: Liu Xiaojun Inventor before: Ma Jie Inventor before: Zhang Lingyu Inventor before: Zhang Jianjun Inventor before: Qimugesudu Inventor before: Yang Huijuan |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |