CN117568231A - 一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 - Google Patents
一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 Download PDFInfo
- Publication number
- CN117568231A CN117568231A CN202311648084.5A CN202311648084A CN117568231A CN 117568231 A CN117568231 A CN 117568231A CN 202311648084 A CN202311648084 A CN 202311648084A CN 117568231 A CN117568231 A CN 117568231A
- Authority
- CN
- China
- Prior art keywords
- liver
- lactobacillus johnsonii
- liver injury
- medicament
- injury
- 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.)
- Pending
Links
- 206010067125 Liver injury Diseases 0.000 title claims abstract description 59
- 231100000753 hepatic injury Toxicity 0.000 title claims abstract description 50
- 241001468157 Lactobacillus johnsonii Species 0.000 title claims abstract description 37
- 239000003814 drug Substances 0.000 claims abstract description 28
- 210000005228 liver tissue Anatomy 0.000 claims abstract description 11
- 210000004969 inflammatory cell Anatomy 0.000 claims abstract description 6
- 230000008595 infiltration Effects 0.000 claims abstract description 5
- 238000001764 infiltration Methods 0.000 claims abstract description 5
- 238000004321 preservation Methods 0.000 claims abstract description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 17
- 208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 231100000234 hepatic damage Toxicity 0.000 claims description 7
- 230000008818 liver damage Effects 0.000 claims description 7
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 5
- 241000186660 Lactobacillus Species 0.000 claims description 3
- 206010019692 hepatic necrosis Diseases 0.000 claims description 3
- 229940039696 lactobacillus Drugs 0.000 claims description 3
- 231100000149 liver necrosis Toxicity 0.000 claims description 3
- 229960005489 paracetamol Drugs 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 7
- 210000004185 liver Anatomy 0.000 abstract description 20
- 241000699670 Mus sp. Species 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 11
- 230000000968 intestinal effect Effects 0.000 abstract description 11
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 10
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 108090000340 Transaminases Proteins 0.000 abstract description 5
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 210000002966 serum Anatomy 0.000 abstract description 5
- 102000014898 transaminase activity proteins Human genes 0.000 abstract description 5
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 abstract description 4
- 108010082126 Alanine transaminase Proteins 0.000 abstract description 4
- 230000003908 liver function Effects 0.000 abstract description 4
- 230000002829 reductive effect Effects 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 239000002158 endotoxin Substances 0.000 abstract description 3
- 244000005700 microbiome Species 0.000 abstract description 3
- 230000003078 antioxidant effect Effects 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 239000003963 antioxidant agent Substances 0.000 abstract 1
- 239000006041 probiotic Substances 0.000 description 8
- 235000018291 probiotics Nutrition 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- 206010019851 Hepatotoxicity Diseases 0.000 description 6
- 231100000304 hepatotoxicity Toxicity 0.000 description 6
- 230000007686 hepatotoxicity Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 2
- 206010072268 Drug-induced liver injury Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 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 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 230000007175 bidirectional communication Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000005118 dietary health Nutrition 0.000 description 1
- 235000021196 dietary intervention Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical compound ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明公开一株约氏乳杆菌BW002及其在防治和/或修复肝损伤中的应用,属于微生物技术领域。本发明约氏乳杆菌(Lactobacillus johnsonii)BW002(保藏于中国典型培养物保藏中心,保藏编号为CCTCC NO:M 20231782)作为缓解肝损伤的辅助药物,能够改善肝损伤小鼠肝功能、抗氧化指标、降低血清内毒素水平及调节肠道菌群分布,肝损伤小鼠血液的谷丙转氨酶(ALT)、谷草转氨酶(AST)都明显升高,提示肝损伤,而使用了约氏乳杆菌BW002后,ALT和AST都降低,逆转了肝损伤生化指标,减轻了药物对肝脏的毒性作用,还降低了小鼠肝组织中的肝脏坏死面积和炎症细胞浸润程度,降低了小鼠肝损伤的程度、炎症的严重性。说明了约氏乳杆菌BW002可以有效地缓解肝损伤相关的病症。
Description
技术领域
本发明属于微生物技术领域,具体涉及一株约氏乳杆菌BW002及其在防治和/或修复肝损伤中的应用。
背景技术
肝脏是体内重要的实质性器官,负担人体的重要生理功能。目前,各种原因导致的肝损伤已成为威胁人类健康的常见疾病之一。常见的肝损伤原因包括:化学性肝损伤、免疫性肝损伤、酒精性肝损伤、药物性肝损伤等等。各种肝损伤的发病原因和机制各有不同,但都是对肝脏组织和肝细胞造成了难以逆转的损害,严重的时候肝功能极度受损,会危及生命。化学性肝损伤常见的有一些化学毒物,例如CCl4、D-氨基半乳糖、亚硝胺等引起。这些化学毒物可以蓄积在肝组织中,促进肝脏部位产生大量炎症因子,导致炎症反应持续进行,增加肝脏星形胶质细胞的激活,产生肝纤维化与肝细胞坏死。免疫性肝损伤常见于自身免疫性肝炎以及病毒性肝炎免疫性肝损害的病人体内。免疫性肝损伤的主要参与细胞是CD4 T细胞与自然杀伤T细胞。这些免疫细胞在病人体内大量活化,释放大量致炎细胞因子,进一步激活体内的其它炎症细胞,如单核细胞、Kupffer细胞等等,最终在肝脏部位造成过度激活的炎症反应,损伤肝实质细胞。酒精性肝损伤是由于过量长期过量饮酒导致。乙醇进入体内,主要的代谢途径是在肝脏内将乙醇转变为乙醛,再使乙醛转化为乙酸,进行代谢。乙醛可诱导肝脏发生氧化应激,损害线粒体和微管,可以诱导肝细胞发生凋亡或坏死。药物性肝损伤常见于对乙酰氨基酚、利福平、异烟肼等临床常用药,在病人体内引发的肝脏转氨酶升高,肝组织炎症坏死等。主要是由于这些药物在肝细胞中激活了线粒体氧化应激,导致钙稳态失衡,增加了促炎信号而抑制了抗炎信号,最终导致肝细胞坏死。
虽然上述肝损伤的产生原因各不相同,但它们都有一些一致的病理现象,包括AST、ALT转氨酶升高,肝组织产生大量炎症因子,肝细胞变性、凋亡或坏死等等。这些病理现象在各种肝损伤中都很常见,因此,临床上治疗肝损伤也大都使用的是降低转氨酶、降低炎症的相关药物。但由于这些抗肝损伤的药物也绝大部分是经由肝脏代谢的,这对于已经发生肝损伤的病人来说,无疑加重了他们的肝脏负担,让本就损伤的肝脏不堪重负,并且目前临床上使用的抗肝损伤药物的使用时间都比较长,有可能保护性作用还未发挥就会带来新的副作用,加剧肝脏损伤,因此需要寻找新的治疗方式和手段,来改善肝损伤。
益生菌是指在其摄入一定数量后,能够促进动物或人体原生微生物菌群生长而对宿主产生有益影响的活性微生物。所述益生菌主要包括乳杆菌、双歧杆菌和肠球菌等;它们一般具备特殊的生理活性和保健功能,例如调节宿主的肠道菌群,治疗由抗生素引起的腹泻,降低血脂胆固醇水平,抑制大肠杆菌、幽门螺杆菌等有害菌的感染等。此外,益生菌能够有效清除自由基,提高机体的抗氧化活性;能够调节肠道菌群,降低内毒素含量;同时,益生菌还能够调节机体的免疫系统。益生菌的这些功能为人们提示,其对于缓解药源性肝损伤能够发挥一定的作用。
肠道及肠道菌群与肝脏之间的双向交流关系决定了肠道菌群与药物肝毒性之间的密切联系,肠道菌群组成、肠道屏障功能、肠道代谢酶及肠道代谢物等对药物肝毒性都有一定的影响。此外,肠道菌群及相关代谢物还可通过作用于肝脏中的核受体,影响Ⅱ相解毒酶等的表达,从而对药物肝毒性产生影响。充分理解肠道菌群与药物肝毒性之间的相关性,揭示肠道菌群影响药物肝毒性的机制,有助于将肠道菌群作为靶点降低药物肝毒性的研究与应用。而目前有关益生菌保肝护肝方面的报道相对较少,因此,探索利用益生菌作为食疗性的保健食品来缓解肝损伤具有重要的研究意义,随着人们对肝损伤的日益重视以及益生菌的不断推广应用,利用益生菌及其产品对肝损伤进行膳食干预将具有极为广阔的市场前景。
发明内容
本发明的目的是提供一种约氏乳杆菌BW002(保藏编号为CCTCC NO:M 20231782)及其在防治和/或修复肝损伤中的应用,降低了肝组织中的肝脏坏死面积和炎症细胞浸润程度,有效地缓解了肝损伤相关的病症。
为实现上述目的,本发明提供了如下方案:
本发明提供了一种约氏乳杆菌(Lactobacillus johnsonii)BW002,所述约氏乳杆菌BW002保藏于中国典型培养物保藏中心,保藏编号为CCTCC NO:M 20231782。保藏日期:2023年9月25日,地址,武汉大学
本发明还提供了一种所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用。
进一步的,所述的约氏乳杆菌BW002用于改善APAP导致的ALT和AST升高。
进一步的,所述的约氏乳杆菌BW002用于改善APAP导致的肝组织中的炎症细胞浸润和肝脏坏死。
进一步的,所述的约氏乳杆菌BW002用于改善APAP导致的炎症因子的升高。
进一步的,所述肝损伤为APAP诱导肝损伤。
进一步的,所述药物的剂型选自粉剂、片剂、颗粒剂、胶囊剂、溶液剂、乳剂、混悬剂中的至少一种。
进一步的,所述药物的给药方式为口服。
本发明公开了以下技术效果:
本发明提供的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,约氏乳杆菌BW002作为缓解肝损伤的辅助药物,能够改善肝损伤小鼠肝功能、抗氧化指标、降低血清内毒素水平及调节肠道菌群分布,肝损伤小鼠血液的ALT、AST都明显升高,提示肝损伤,而使用了约氏乳杆菌BW002后,ALT和AST都降低,逆转了肝损伤生化指标,减轻了药物对肝脏的毒性作用,还降低了小鼠肝组织中的肝脏坏死面积和炎症细胞浸润程度以及小鼠肝组织中的炎症因子,降低了小鼠肝损伤的程度、炎症的严重性。说明了约氏乳杆菌BW002可以有效地缓解肝损伤相关的病症。
附图说明
为了更清楚地说明本发明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发明的一些实施例,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为经约氏乳杆菌BW002处理后的小鼠组织形态分析图;其中,左图为APAP诱导后的小鼠肝脏组织,右图为经约氏乳杆菌BW002处理后的小鼠肝脏组织;
图2为经约氏乳杆菌BW002处理后的HE染色分析图;其中,左图为经约氏乳杆菌BW002处理与不经约氏乳杆菌BW002处理后的染色对比图,右图为肝脏坏死面积对比柱状图;
图3为经约氏乳杆菌BW002处理后的谷丙转氨酶(ALT)和谷草转氨酶(AST)含量图;其中,左图为ALT含量图,右图为AST含量图;
图4为经约氏乳杆菌BW002处理后的IL-6和TNF-α含量图;其中,左图为IL-6含量图,右图为TNF-α含量图。
具体实施方式
现详细说明本发明的多种示例性实施方式,该详细说明不应认为是对本发明的限制,而应理解为是对本发明的某些方面、特性和实施方案的更详细的描述。
下面将结合具体实施例对本发明的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例1
(1) 准备WT小鼠
从北京维通利华司购买12只8周龄的野生型C57/BL6小鼠,饲养于SPF屏障系统内,适应一周后将小鼠随机分成2组,分别为生理盐水-APAP对照组(阴性对照组)、约氏乳杆菌BW002-APAP处理组(阳性对照组),约氏乳杆菌BW002保藏于中国典型培养物保藏中心,保藏编号为CCTCC NO:M 20231782。
(2) 约氏乳杆菌BW002肠道定植
将约氏乳杆菌BW002接种于液态MRS培养基中,于37℃条件下厌氧、静置培养20-22h,然后8000rpm离心5min收集菌体,用生理盐水洗涤两次后,再将细菌重悬于生理盐水中,终浓度约10×109 CFU/mL。按照每只小鼠200μL菌的剂量灌胃处理WT小鼠,隔天重复处理,持续1周,同时生理盐水-APAP对照组仅进行生理盐水灌胃处理。1周的灌胃处理结束后,小鼠即可进行诱导肝损伤实验。
(3) 建立小鼠APAP诱导肝损伤模型
小鼠在禁食过夜(16小时)后,可以自由饮水。接着,小鼠通过灌胃方式给予300mg/kg的对乙酰氨基酚,溶解在含有50%聚乙二醇的磷酸盐缓冲盐水(HBSS)中。整个实验过程中,对小鼠进行观察。诱导后的24小时,进行相关检测。
药物诱导24h后,颈椎脱臼法处死小鼠,取出小鼠肝脏部分,进行福尔马林固定,并后续进行组织形态分析和HE染色,所得结果如图1所示,可见对照组肝脏组织出现明显坏死区域,图2 HE染色分析可见,肝脏坏死面积和炎症细胞浸润程度在BW002组明显降低,说明BW002明显缓解了肝脏损伤。
采集APAP诱导后24小时的血清进行生化分析,血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)使用生化仪器进行测定,IL-6,TNF-α使用Elisa试剂盒进行测定。
谷丙转氨酶(ALT)和谷草转氨酶(AST)常用于评估肝功能和肝损伤的生化指标,通常用于诊断和监测肝脏健康状况,根据图3所示,BW002明显降低了小鼠血清中的ALT和AST,减轻了药物对肝脏的毒性作用
IL-6和TNF-α是经典的炎症因子,它们在肝损伤模型中的升高可能反映了炎症和免疫反应的激活,根据图4结果所示,BW002明显降低了小鼠肝组织中的炎症因子,降低了小鼠肝损伤的程度、炎症的严重性。
当然,上述说明也并不仅限于上述举例,本发明未经描述的技术特征可以通过或采用现有技术实现,在此不再赘述:以上实施例及附图仅用于说明本发明的技术方案并非是对本发明的限制,参照优选的实施方式对本发明进行了详细说明,本领域的普通技术人员应当理解,本技术领域的普通技术人员在本发明的实质范围内所做出的变化、改型、添加或替换都不脱离本发明的宗首,也应属于本发明的权利要求保护范围。
Claims (8)
1.一种约氏乳杆菌(Lactobacillus johnsonii)BW002,其特征在于,所述约氏乳杆菌BW002保藏于中国典型培养物保藏中心,保藏编号为CCTCC NO:M 20231782。
2.如权利要求1所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用。
3.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述的约氏乳杆菌BW002用于改善对乙酰氨基酚(APAP)导致的ALT和AST升高。
4.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述的约氏乳杆菌BW002用于改善APAP导致的肝组织中的炎症细胞浸润和肝脏坏死。
5.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述的约氏乳杆菌BW002用于改善APAP导致的炎症因子的升高。
6.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述肝损伤为APAP诱导肝损伤。
7.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述药物的剂型选自粉剂、片剂、颗粒剂、胶囊剂、溶液剂、乳剂、混悬剂中的至少一种。
8.根据权利要求2所述的约氏乳杆菌BW002在制备防治和/或修复肝损伤的药物中的应用,其特征在于,所述药物的给药方式为口服。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311648084.5A CN117568231A (zh) | 2023-12-05 | 2023-12-05 | 一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311648084.5A CN117568231A (zh) | 2023-12-05 | 2023-12-05 | 一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117568231A true CN117568231A (zh) | 2024-02-20 |
Family
ID=89888070
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311648084.5A Pending CN117568231A (zh) | 2023-12-05 | 2023-12-05 | 一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN117568231A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115737690A (zh) * | 2022-11-11 | 2023-03-07 | 重庆医科大学 | 约氏乳杆菌在制备用于缓解急性呼吸窘迫综合征的药物中的应用 |
-
2023
- 2023-12-05 CN CN202311648084.5A patent/CN117568231A/zh active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115737690A (zh) * | 2022-11-11 | 2023-03-07 | 重庆医科大学 | 约氏乳杆菌在制备用于缓解急性呼吸窘迫综合征的药物中的应用 |
CN115737690B (zh) * | 2022-11-11 | 2024-04-19 | 重庆医科大学 | 约氏乳杆菌在制备用于缓解急性呼吸窘迫综合征的药物中的应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6673843B2 (en) | Curcumin and curcuminoid inhibition of angiogenesis | |
CN117568231A (zh) | 一株约氏乳杆菌bw002及其在防治和/或修复肝损伤中的应用 | |
CN109419814B (zh) | 戈氏副拟杆菌用于抑制脂肪肝疾病的用途 | |
CN111166734A (zh) | 萘醌类物质治疗病原性生物引起的肺炎的用途 | |
CN115089619A (zh) | 植物乳杆菌zdy2013在具有缓解非酒精性脂肪肝功能的制剂中的应用 | |
WO2007009392A1 (fr) | Utilisation d'acide chlorogenique dans la fabrication de medicaments pour le traitement et/ou la prevention de trouble hepatique | |
WO2021164523A1 (zh) | 阿克曼氏菌组合物 | |
CN115607577B (zh) | 一种具有缓解口腔炎症功效的益生菌剂及其制备方法和应用 | |
AU2018446089B2 (en) | Pharmaceutical use of anemoside B4 against acute gouty arthritis | |
TWI725317B (zh) | 新穿心蓮內酯之組成物用於血糖調降之應用 | |
CN116854775A (zh) | 一种神经保护多肽及其应用 | |
WO2022089591A1 (zh) | 氨基葡萄糖在制备治疗非酒精性脂肪性药物中的应用 | |
CN117442649A (zh) | 一株能够防治和/或修复肝损伤及相关疾病的植物乳植杆菌pm001 | |
CN113648311B (zh) | 7-(2,2-二甲基-3-丁烯酰胺基)-八氢苯喹啉乙酸酯在制备降脂药物中的应用 | |
CN114621896A (zh) | 一株具有降糖降脂功能的植物乳杆菌84-3及其应用 | |
CA3104916C (en) | Pharmaceutical composition for preventing diabetes and use thereof | |
CN109875990A (zh) | 一种含对香豆酸的药用组合物及其应用 | |
KR20190068068A (ko) | 비만 억제 활성을 갖는 페디오코커스 에시디락티시 ao22 균주 및 이를 포함하는 비만 개선 또는 치료용 조성물 | |
CN116650577B (zh) | 一种锦灯笼提取物在抗鸡传染性支气管炎病毒中的应用 | |
CN110693876B (zh) | 穿心莲内酯在制备预防或/和治疗肌肉损伤的药物中的应用 | |
CN116421599A (zh) | 吲哚-3-甲醛在制备电离辐射致肠损伤防护药物中的应用 | |
KR20230083871A (ko) | 레몬 껍질 발효물을 포함하는 항비만 조성물 | |
CN115105527A (zh) | 药物组合物及其用途 | |
Wang et al. | Raspberry ketone improves diabetic nephropathy in mice by inhibiting streptozotocin-induced oxidative stress and inflammation | |
CN117618481A (zh) | 傣百解提取物及其制剂在解酒护肝等相关疾病中的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication |