CN113832077A - 鼠李糖乳杆菌及其应用 - Google Patents
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- CN113832077A CN113832077A CN202111290310.8A CN202111290310A CN113832077A CN 113832077 A CN113832077 A CN 113832077A CN 202111290310 A CN202111290310 A CN 202111290310A CN 113832077 A CN113832077 A CN 113832077A
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- lactobacillus rhamnosus
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- lactobacillus
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Abstract
本发明公开了一株鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX‑01,其保藏编号为GDMCC No:60986。本发明的鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX‑01具备益生菌的一般特性,具有良好的耐胃酸性能,以及良好的胃粘膜黏附性。鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX‑01可抑制幽门螺杆菌在胃肠道中的粘附定植,能有效抑制幽门螺杆菌生长,抑制炎症反应,帮助修复胃黏膜组织,维持胃肠道微生态平衡。
Description
技术领域
本发明属于生物技术领域,特别是涉及一株鼠李糖乳杆菌Lactobacillusrhamnosus LRX-01及其应用。
背景技术
幽门螺杆菌(Helicobacter pylori,H.pylori)为革兰氏阴性菌,主要在人的胃及十二指肠中生存,是导致活动性胃炎、消化性溃疡、胃癌、胃黏膜相关淋巴组织淋巴瘤等消化系统疾病的重要病因之一,已被世界卫生组织国际癌症研究机构确认为Ⅰ类致癌因子。近期的研究结果表明,幽门螺杆菌还可能与心血管、皮肤、神经、免疫、血液、肝胆、呼吸、内分泌及代谢紊乱有关的胃外表现存在关联。对H.pylori感染进行有效的干预和控制,从而预防胃癌以及降低其它H.pylori相关性疾病的发生率已经是全球公共卫生需要。
最初根除H.pylori的一线方案为经典铋剂四联,随着标准三联疗法[质子泵抑制剂(proton pump inhibitor,PPI)+阿莫西林+克拉霉素]表现出疗效高、服药少、不良反应发生率低的优势,很快成为根除H.pylori的新的一线治疗方案,但随着克拉霉素耐药率的不断升高,标准三联疗法根除H.pylori的疗效逐渐降低。虽然药物一直在更新换代,但未见临床疗效提高,此外抗生素本身亦会引起各种不良反应,如肠道菌群失调、胃肠功能紊乱等,限制了其广泛应用。如果初次或多次治疗后失败,再进行治疗时能够选择的药物更加稀少。
益生菌是一类对宿主有益的活性微生物,能定植于肠道、生殖系统中,在改善微生态平衡中发挥了重要的作用,近年来人们不断尝试在H.pylori根除治疗中联合应用微生态疗法,并已发现某些益生菌菌株能抑制H.pylori的生长。
鼠李糖乳杆菌(Lactobacillus rhamnosusGG,LGG)为乳杆菌属、鼠李糖杆菌种,是无质粒、厌氧耐酸、不产芽孢的革兰氏阳性菌,大多存在于人和动物肠道内,具有耐酸、耐胆汁盐、耐多种抗生素等生物学特点。有大量的实验表明,鼠李糖乳杆菌能耐受宿主消化道环境,肠道黏着率高,定植于宿主肠道内调节肠道菌群,有降低胆固醇、预防和治疗胃肠道感染和腹泻、排除毒素、预防龋齿和增强免疫力等作用,已成为国际上文献记载最多和应用最广的益生菌之一。
另有文献表明,鼠李糖乳杆菌可能通过下调MAPK,JAK/STAT,NF-kB途径中磷酸化蛋白的表达水平,抑制炎症因子IL-8的表达,从而起到抑制H.pylori感染性胃炎的作用。乳杆菌能够抑制H.pylori在胃中的定植并改善H.pylori感染导致的胃炎,并且通过影响H.pyloricagA毒力蛋白抑制胃上皮细胞分泌IL-8的水平。
但是鼠李糖乳杆菌LGG,其耐受胃酸能力和胃内定植能力较差,较难定植在胃组织发挥抑制H.pylori的作用。因此,筛选出有良好胃黏膜黏附性、耐受胃酸的鼠李糖乳杆菌非常重要。
发明内容
基于此,本发明的目的是提供一种鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01,所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01具备益生菌的一般特性,良好的胃粘膜黏附性,能够抑制幽门螺杆菌生长。
实现上述发明目的的具体技术方案如下:
一种鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01,保藏于广东省微生物菌种保藏中心,保藏编号为GDMCC No:60986。
本发明还提供了上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物。
本发明还提供一种上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01、或上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物在制备预防和/或治疗幽门螺杆菌感染的药物中的应用。
本发明还提供一种上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01、或上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物在制备预防和/或治疗幽门螺杆菌感染引起的胃肠道疾病的药物中的应用。
在其中一些实施例中,所述胃肠道疾病为胃溃疡、胃炎或胃癌。
本发明还提供一种预防和/或治疗幽门螺杆菌感染的产品,其活性成分包括上述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01,或上述鼠李糖乳杆菌(Lactobacillusrhamnosus)LRX-01的培养物或代谢产物。
在其中一些实施例中,所述产品为保健品、食品、药品、菌剂或饲料添加剂。
在其中一些实施例中,所述食品为乳制品、蔬菜制品、饮料制品或其他发酵类制品。
在其中一些实施例中,所述保健品为液体状保健品、颗粒状保健品、粉末状保健品、胶囊状保健品或片状保健品。
在其中一些实施例中,所述产品为药品,所述药品还包括药学上可接受的辅剂,所述辅剂为稳定剂、湿润剂、乳化剂、粘合剂、等渗剂中的一种或几种。
在其中一些实施例中,所述药品的剂型为片剂、颗粒剂、散剂、胶囊剂、溶液剂、悬浮剂、或冻干制剂。
与现有技术相比,本发明具有以下有益效果:
本发明的鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01是从健康新生儿粪便中分离出的乳杆菌属的另一种亚型,从细菌来源保证其安全性及有效性,其具备益生菌的一般特性,具有良好的耐胃酸性,以及良好的胃粘膜黏附性,可抑制幽门螺杆菌在胃肠道中的粘附定植,能有效抑制幽门螺杆菌生长,抑制炎症反应,帮助修复胃黏膜组织,维持胃肠道微生态平衡。
附图说明
图1是实施例1中分离得到的鼠李糖乳杆菌LRX-01革兰氏染色结果。
图2是实施例1中分离得到的鼠李糖乳杆菌LRX-01的16SrDNA系统进化发育树。
图3是实施例1中分离得到的鼠李糖乳杆菌LRX-01糖酵解生化试验结果。
图4是实施例3中鼠李糖乳杆菌LRX-01黏附胃上皮细胞结果。
图5是实施例4中气相色谱—质谱检测鼠李糖乳杆菌LRX-01的短链脂肪酸结果。
图6是实施例5中牛津杯法测试鼠李糖乳杆菌LRX-01抑制幽门螺杆菌的实验结果。其中左图为:ATCC53103上清液、菌体、菌液所形成的抑菌圈;右图为:鼠李糖乳杆菌LRX-01上清液、菌体、菌液所形成的抑菌圈。
图7是实施例6中鼠李糖乳杆菌LRX-01干预H.pylori感染小鼠后胃组织快速尿素酶实验结果。
图8是实施例6中鼠李糖乳杆菌LRX-01干预H.pylori感染小鼠后胃组织病理切片图。
具体实施方式
本发明下列实施例中未注明具体条件的实验方法,通常按照常规条件,或按照制造厂商所建议的条件。实施例中所用到的各种常用化学试剂,均为市售产品。
除非另有定义,本发明所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本发明的说明书中所使用的术语只是为了描述具体的实施例的目的,不用于限制本发明。
本发明所述的鼠李糖乳杆菌LRX-01,分类命名为Lactobacillus rhamnosus,已于2020年3月26日保藏于广东省微生物菌种保藏中心,保藏编号为GDMCC No:60986,保藏单位地址:广州市先烈中路100号大院59号楼5楼广东省微生物研究所。
本发明的鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01益生菌是从健康新生儿粪便中分离出的乳杆菌属的另一种亚型,鼠李糖乳杆菌(Lactobacillus rhamnosus)是益生菌的一种,目前已被纳入卫生部下发的《可用于食品的菌种名单》,可见,本发明的有效成分为鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的产品不会使得幽门螺杆菌产生耐药性,同时,在治疗过程中不会导致患者产生不良反应。
下述实施例中涉及的幽门螺杆菌为来源于NTCC国家典型培养物保藏中心的幽门螺杆菌SS1;下述实施例中涉及的鼠李糖乳杆菌标准株ATCC 53103(即鼠李糖乳杆菌LGG),来源于美国模式培养物集存库(ATCC),保藏编号为ATCC 53103。
下述实施例中涉及的培养基如下:
MRS固体培养基(g/L):蛋白胨10g/L、牛肉膏10g/L、葡萄糖20g/L、乙酸钠5g/L、酵母提取物5g/L、柠檬酸氢二铵2g/L、K2HPO42g/L、MgSO4·7H2O0.58g/L、MnSO40.05g/L、吐温801mL/L、琼脂15g/L~17g/L,pH6.12~6.2。
MRS肉汤培养基(g/L):蛋白胨10g/L、牛肉膏10g/L、葡萄糖20g/L、乙酸钠5g/L、酵母提取物5g/L、柠檬酸氢二铵2g/L、K2HPO42g/L、MgSO4·7H2O0.58g/L、MnSO40.05g/L、吐温801mL/L,pH6.12~6.2。
以下结合具体实施例和附图对本发明进行进一步说明。
实施例1鼠李糖乳杆菌LRX-01的分离鉴定
1、鼠李糖乳杆菌LRX-01的分离
包括以下步骤:
(1)、收集纯母乳喂养的健康新生儿新鲜粪便,按固液比为1:1000(g/ml)的比例加入PBS稀释;
(2)、取5μl稀释后的样本涂布于MRS固体培养基,37℃恒温厌氧培养48h;
(3)、根据菌落的颜色、大小、边缘形状等,用接种环挑取菌落,划线纯化;
(4)、挑取单菌落,接种至MRS液体培养基,增菌培养,即得。
2、菌株的形态学特征
菌落特征:菌落生长良好,为乳白色,圆型,凸起,边缘整齐。
菌体特征:短小的杆状,不运动,无芽孢,兼性厌氧,革兰氏染色阳性(如图1所示)。
3、菌株的分子生物学鉴定
用细菌基因组DNA试剂盒(TIANamp Bacteria DNA Kit)提取细菌总DNA,提取方法步骤根据试剂盒说明书进行。使用乳酸菌16SrDNA的通用引物(引物由上海生工生物有限公司合成)对提取的DNA进行PCR扩增。
16SrDNA的通用引物对核苷酸序列为:
正向引物27f:5'-AGAGTTTGATCCTGGCTCAG-3'(SEQ ID NO:1)反向引物1492r:5'-GGTTACCTTGTTACGACTT-3'(SEQ ID NO:2)
PCR扩增反应体系共20μl,DNA模板2μl,TaKaRa Premix TaqTM 10μl,正向引物、反向引物各1μl,dd H2O 6μl。阴性对照(control)反应体系中,模板以ddH2O代替,其余成分一样。
PCR扩增反应条件:94℃5min;94℃60s,60℃60s,72℃90s,30个循环;72℃10min;4℃保存。
PCR电泳后进行切胶,回收目的条带凝胶并由上海生工生物有限公司测序。在美国NCBI数据库,应用BLAST软件工具对菌株16SrDNA基因序列进行比对,并用MEGAX构建系统发育树。
结果如图2所示,从图2可以看出,本实施例中分离得到的菌株的测序结果,与鼠李糖乳杆菌的16SrDNA序列同源性达到99%,鉴定本实施例中分离得到的菌株属于鼠李糖乳杆菌Lactobacillus rhamnosus,命名为LRX-01。核苷酸序列如SEQ ID No:3所示。
GCGGGGCGGGTGCTATACATGCAGTCGAACGAGTTCTGATTATTGAAAGGTGCTTGCATCTTGATTTAATTTTGAACGAGTGGCGGACGGGTGAGTAACACGTGGGTAACCTGCCCTTAAGTGGGGGATAACATTTGGAAACAGATGCTAATACCGCATAAATCCAAGAACCGCATGGTTCTTGGCTGAAAGATGGCGTAAGCTATCGCTTTTGGATGGACCCGCGGCGTATTAGCTAGTTGGTGAGGTAACGGCTCACCAAGGCAATGATACGTAGCCGAACTGAGAGGTTGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATCTTCCACAATGGACGCAAGTCTGATGGAGCAACGCCGCGTGAGTGAAGAAGGCTTTCGGGTCGTAAAACTCTGTTGTTGGAGAAGAATGGTCGGCAGAGTAACTGTTGTCGGCGTGACGGTATCCAACCAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGATTTATTGGGCGTAAAGCGAGCGCAGGCGGTTTTTTAAGTCTGATGTGAAAGCCCTCGGCTTAACCGAGGAAGTGCATCGGAAACTGGRAAACTTGAGTGCAGAAGAGGACAGTGGAACTCCATGTGTAGCGGTGAAATGCGTAGATATATGGAAGAACACCAGTGGCGAAGGCGGCTGTCTGGTCTGTAACTGACGCTGAGGCTCGAAAGCATGGGTAGCGAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGAATGCTAGGTGTTGGAGGGTTTCCGCCCTTCAGTGCCGCAGCTAACGCATTAAGCATTCCGCCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCTTTTGATCACCTGAGAGATCAGGTTTCCCCTTCGGGGGCAAAATGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATGACTAGTTGCCAGCATTTAGTTGGGCACTCTAGTAAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGATGGTACAACGAGTTGCGAGACCGCGAGGTCAAGCTAATCTCTTAAAGCCATTCTCAGTTCGGACTGTAGGCTGCAACTCGCCTACACGAAGTCGGAATCGCTAGTAATCGCGGATCAGCACGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTTTGTAACACCCGAAGCCGGTGGCGTAACCCTTTTAGGGAGCGAGCCGTCTAAGGTGAACAAAA(SEQ ID NO:3)
4、糖发酵实验进行菌株鉴定
利用糖发酵实验对菌株进行鉴定,根据新型微生物微量生化系列鉴定管说明书进行操作,检测本实施例分离所得的菌株LRX-01的生化代谢物。结果如表1和图3所示。从表1和图3可知,该菌种的生理生化特征与鼠李糖乳杆菌标准株ATCC53103的生理生化性质基本一致。
表1本实施例分离得到的菌株的生化鉴定结果
生化管分类 | ATCC53103 | LRX-01 |
甘露醇 | + | + |
水杨苷 | + | + |
山梨醇 | + | + |
棉子糖 | - | - |
麦芽糖 | - | - |
蔗糖 | - | - |
纤维二糖 | + | + |
菊糖 | + | + |
七叶苷 | - | - |
乳糖 | - | - |
注:“+”为反应阳性,“-”为反应阴性。
综上,根据形态学特征、分子生物学鉴定和糖发酵实验结果,将本发明实施例1中分离筛选到的菌株鉴定为鼠李糖乳杆菌,该菌株于2020年03月26日保藏于广东省微生物菌种保藏中心,分类命名为:Lactobacillus rhamnosus LRX-01,保藏编号为GDMCC No:60986。
实施例2本发明的鼠李糖乳杆菌LRX-01对人工胃液的耐受作用试验
分别配制pH值为2.0,3.0,4.0的人工胃液。分别取鼠李糖乳杆菌标准株ATCC53103和本发明的鼠李糖乳杆菌LRX-01,用无菌PBS稀释为109CFU/ml的菌悬液。吸取菌悬液10μl于990μl不同pH值的人工胃液中,37℃厌氧培养1h~3h,使用稀释滴板法测定初始与培养后的活菌数。结果如表2所示。
表2 ATCC53103与LRX-01耐受人工胃液性能比较
菌株 | pH2 | pH3 | pH4 |
ATCC53103 | 1.30%±0.14% | 94.80%±4.09% | 96.48%±2.73% |
LRX-01 | 2.09%±0.07% | 97.35%±2.51% | 97.37%±4.05% |
从表2可知,与鼠李糖乳杆菌标准株ATCC53103相比,本发明的鼠李糖乳杆菌LRX-01表现出更好的耐人工胃液能力。
实施例3本发明的鼠李糖乳杆菌LRX-01黏附胃上皮细胞能力试验
包括以下步骤:
(1)、细胞复苏与传代:从液氮灌中取出胃上皮细胞GES-1,快速置于37℃水浴箱中晃动直至完全融化,无菌操作吸取细胞悬液到15ml无菌离心管中,缓慢加入适量GES-1完全细胞培养基,1000rpm离心5min,弃上清后加入5ml完全培养基,置于37℃,5%CO2培养箱中培养;待细胞汇合率达80%-90%后,用无菌PBS漂洗残留血清和培养基,加入1ml0.25%含EDTA的胰蛋白酶消化细胞,数分钟后显微镜下见细胞变圆脱落,立即加入完全培养液10ml终止消化,用滴管轻轻吹打细胞成单个细胞,转接至3个新的T25细胞培养瓶中。
(2)、细胞计数以及准备黏附实验用细胞:将培养于细胞培养瓶的细胞按上述步骤消化并稀释,取适量细胞悬液滴加到血球计数仪中,显微镜下观察计数四大格细胞总数,调整细胞浓度,按每孔接种细胞数约1×104/ml的浓度接种于24孔板,十字法轻柔晃动,使细胞均匀铺于24孔板中,置于37℃,5%CO2环境中培养。
(3)、取出培养于24孔板的GES-1,用无菌PBS漂洗,去除残留血清和双抗,然后加入DMEM基础培养基(不含双抗和胎牛血清),进行分组,包括对照组(GES-1+H.pylori共孵育3h)、ATCC53103组(GES-1+H.pylori+ATCC53103共孵育3h)、LRX-01组(GES-1+H.pylori+LRX-01共孵育3h)。然后吸除处理液,用PBS轻柔清洗3次,加入150μl 0.5%Triton-X100,置于37℃下裂解细胞8min,补加850μl无菌蒸馏水,用加样枪头反复吹打,然后吸出置于无菌EP管中,10倍梯度稀释并涂BHI平板,37℃培养过夜;计算菌落数,实验重复3次;计算细菌相对黏附率,相对黏附率=(实验组的菌落数×稀释倍数/对照组的菌落数)×100%。
结果如图4所示,从图4可以看出,与鼠李糖乳杆菌标准株ATCC53103相比,本发明的鼠李糖乳杆菌LRX-01表现出更好的胃上皮细胞黏附能力,黏附率明显高于鼠李糖乳杆菌标准株ATCC53103。
实施例4本发明的鼠李糖乳杆菌LRX-01产短链脂肪酸的能力测试
分别配制如下待测溶液:
(1)、取调至OD600=1的鼠李糖乳杆菌LRX-01菌液100μl加到8mlMRS肉汤培养基中培养24h,取菌悬液1mL于1.5mL离心管,10000rpm/min离心2min,取上清100μl,加入5μl内标(IS),5μl去离子水,150μl甲醇,40μl2.5%H2SO4,0.05g无水硫酸钠,涡旋1.5min,离心(14000rpm,室温,5min);取上清于装有衬管的进样小瓶,待测。
(2)、取调至OD600=1的鼠李糖乳杆菌标准株ATCC53103菌液100μl加到8ml MRS肉汤培养基中培养24h,取菌悬液1mL于1.5mL离心管,10000rpm/min离心2min,取上清100μl,加入5μl内标(IS),5μl去离子水,150μl甲醇,40μl2.5%H2SO4,0.05g无水硫酸钠,涡旋1.5min,离心(14000rpm,室温,5min);取上清于装有衬管的进样小瓶,待测。
(3)、配制随行空白样本:取100μl生理盐水,加入5μl内标(IS),5μl去离子水,150μl甲醇,40μl2.5%H2SO4,0.05g无水硫酸钠,涡旋1.5min,离心(14000rpm,室温,5min),取上清于装有衬管的进样小瓶,待测。
(4)、配制质控样本:取100μl生理盐水,加入5μl内标(IS),5μl STD-4,150μl甲醇,40μl2.5%H2SO4,0.05g无水硫酸钠,涡旋1.5min,离心(14000rpm,室温,5min),取上清于装有衬管的进样小瓶,待测。
气相色谱-质谱(GC-MS)测定上述(1)-(4)各处理中的短链脂肪酸含量。
结果如图5所示,从图5可以看出,与鼠李糖乳杆菌标准株ATCC53103相比,本发明的鼠李糖乳杆菌LRX-01表现出更好的产短链脂肪酸能力,短链脂肪酸总量更高,尤其丙酸、丁酸、庚酸产量较高。
实施例5本发明的鼠李糖乳杆菌LRX-01对幽门螺杆菌生长的抑制作用
包括以下步骤:
1、吸取幽门螺杆菌悬液(OD600=1)200μl至血平板中,用无菌涂布棒涂布均匀,并用镊子将3个无菌牛津杯放置到平板中;如此设置两个血平板;
2、吸取鼠李糖乳杆菌标准株ATCC53103悬液(OD600=1)100μl至上述1个血平板的1个牛津杯中(注意液体不要溢出至牛津杯外);吸取鼠李糖乳杆菌标准株ATCC53103悬液(OD600=1)100μl,8000rpm离心5min后弃去上清,用100μl的PBS重悬离心后的菌体后,加至上述血平板的第2个牛津杯中(注意液体不要溢出至牛津杯外);吸取鼠李糖乳杆菌标准株ATCC53103悬液(OD600=1)120μl,8000rpm离心5min,将上清液100μl加至上述血平板的第3个牛津杯中(注意液体不要溢出至牛津杯外);将血平板放于37℃,微需氧环境中培养48h。
3、吸取本发明的鼠李糖乳杆菌LRX-01悬液(OD600=1)100μl至上述另1个血平板的1个牛津杯中(注意液体不要溢出至牛津杯外);吸取鼠李糖乳杆菌LRX-01悬液(OD600=1)100μl,8000rpm离心5min后弃去上清,用100μl的PBS重悬离心后的菌体后,加至上述血平板的第2个牛津杯中(注意液体不要溢出至牛津杯外);吸取鼠李糖乳杆菌LRX-01悬液(OD600=1)120μl,8000rpm离心5min,将上清液100μl加至上述血平板的第3个牛津杯中(注意液体不要溢出至牛津杯外);将血平板放于37℃,微需氧环境中培养48h。
4、培养结束后,分别测定两个血平板中鼠李糖乳杆菌标准株ATCC53103和鼠李糖乳杆菌LRX-01的菌液、菌体和上清液对幽门螺杆菌的抑菌圈大小。
结果如表3和图6所示。
表3 ATCC53103与LRX-01抑制幽门螺杆菌牛津杯实验
菌株 | 上清液(mm) | 菌液(mm) | 菌体(mm) |
ATCC53103 | 9±1.0 | 11±1.0 | 7±0.5 |
LRX-01 | 22±2.0 | 25±2.0 | 15±1.0 |
从表3和图6可以看出,鼠李糖乳杆菌LRX-01上清、菌液和菌体在平板中形成的抑菌圈直径,比鼠李糖乳杆菌标准株ATCC53103上清、菌液和菌体在平板中形成的抑菌圈直径都要大,说明LRX-01相较于ATCC53103,对幽门螺杆菌具有更强的抑制作用,其中LRX-01的菌液形成的抑菌圈直径达到了25±2.0mm,上清液形成的抑菌圈直径达到了22±2.0mm。
实施例6本发明的鼠李糖乳杆菌LRX-01对幽门螺杆菌感染性胃炎的缓解作用
包括以下步骤:
(1)、4周龄C57BL/6小鼠24只,正常饲养一周后随机分成4组:Control组(n=6),H.pylori感染组(n=6),H.pylori感染+鼠李糖乳杆菌标准株ATCC53103处理组(n=6),H.pylori感染+鼠李糖乳杆菌LRX-01处理组(n=6)。
(2)、第1至3天,各组小鼠禁食12h后进行0.2ml三联抗生素(氨苄青霉素2.75mg+阿奇霉素2.75mg+庆大霉素0.3mg)灌胃,间隔2小时再次0.2ml三联混合抗生素灌胃,4小时后Control组和H.pylori感染组灌胃空白MRS肉汤0.2ml,H.pylori感染+鼠李糖乳杆菌标准株ATCC53103组和H.pylori感染+鼠李糖乳杆菌LRX-01组分别灌胃OD600=1的ATCC53103和LRX-01菌液0.2ml,解除禁水禁食。
(3)、第4天,各组小鼠禁食12h后予0.08ml50%乙醇灌胃,间隔2小时Control组和H.pylori感染组灌胃空白MRS肉汤0.2ml,H.pylori感染+鼠李糖乳杆菌标准株ATCC53103组和H.pylori感染+鼠李糖乳杆菌LRX-01组分别灌胃OD600=1的ATCC53103和LRX-01菌液0.2ml;6小时后Control组灌胃空白肉汤培养基0.2ml,其他组均灌胃OD600=1新鲜H.pylori混悬液0.2ml,解除禁水禁食。
(4)、第5天-32天,各组小鼠禁食12h后Control组和H.pylori感染组灌胃空白MRS肉汤0.2ml,H.pylori感染+鼠李糖乳杆菌标准株ATCC53103组和H.pylori感染+鼠李糖乳杆菌LRX-01组分别灌胃OD600=1的ATCC53103和LRX-01菌液0.2ml;6小时后Control组灌胃空白肉汤培养基0.2ml,其他组均灌胃OD600=1新鲜H.pylori混悬液0.2ml,解除禁水禁食。
(5)、第32-59天,各组小鼠禁食12h后Control组和H.pylori感染组灌胃空白MRS肉汤0.2ml,H.pylori感染+鼠李糖乳杆菌标准株ATCC53103组和H.pylori感染+鼠李糖乳杆菌LRX-01组分别灌胃OD600=1的ATCC53103和LRX-01菌液0.2ml,解除禁水禁食。
(6)、第62天解剖各种小鼠,检测各项指标。
各组小鼠胃黏膜组织快速尿素酶检测结果如图7所示,从图7可以看出:H.pylori感染组呈现尿素酶阳性,而Control组、H.pylori感染+鼠李糖乳杆菌标准株ATCC53103组、H.pylori感染+鼠李糖乳杆菌LRX-01组呈现尿素酶阴性,且与LRX-01组相比,ATCC53103组尿素酶溶液更红。说明LRX-01在H.pylori感染小鼠体内能够显著抑制H.pylori,且效果较标准株ATCC53103要好。
HE染色结果如图8所示,图8显示:H.pylori感染组出现囊性变、萎缩,炎症浸润等胃组织病理损伤,H.pylori感染+鼠李糖乳杆菌ATCC53103组出现炎症细胞浸。与H.pylori感染+鼠李糖乳杆菌ATCC53103组相比,H.pylori感染+鼠李糖乳杆菌LRX-01组炎症细胞浸润症状可显著缓解。说明LRX-01能够抑制H.pylori感染,从而减轻幽门螺杆菌性胃炎损伤。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
序列表
<110> 南方医科大学 广州万孚健康科技有限公司
<120> 鼠李糖乳杆菌及其应用
<130> 1
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 1
agagtttgat cctggctcag 20
<210> 2
<211> 19
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 2
ggttaccttg ttacgactt 19
<210> 3
<211> 1471
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 3
gcggggcggg tgctatacat gcagtcgaac gagttctgat tattgaaagg tgcttgcatc 60
ttgatttaat tttgaacgag tggcggacgg gtgagtaaca cgtgggtaac ctgcccttaa 120
gtgggggata acatttggaa acagatgcta ataccgcata aatccaagaa ccgcatggtt 180
cttggctgaa agatggcgta agctatcgct tttggatgga cccgcggcgt attagctagt 240
tggtgaggta acggctcacc aaggcaatga tacgtagccg aactgagagg ttgatcggcc 300
acattgggac tgagacacgg cccaaactcc tacgggaggc agcagtaggg aatcttccac 360
aatggacgca agtctgatgg agcaacgccg cgtgagtgaa gaaggctttc gggtcgtaaa 420
actctgttgt tggagaagaa tggtcggcag agtaactgtt gtcggcgtga cggtatccaa 480
ccagaaagcc acggctaact acgtgccagc agccgcggta atacgtaggt ggcaagcgtt 540
atccggattt attgggcgta aagcgagcgc aggcggtttt ttaagtctga tgtgaaagcc 600
ctcggcttaa ccgaggaagt gcatcggaaa ctggraaact tgagtgcaga agaggacagt 660
ggaactccat gtgtagcggt gaaatgcgta gatatatgga agaacaccag tggcgaaggc 720
ggctgtctgg tctgtaactg acgctgaggc tcgaaagcat gggtagcgaa caggattaga 780
taccctggta gtccatgccg taaacgatga atgctaggtg ttggagggtt tccgcccttc 840
agtgccgcag ctaacgcatt aagcattccg cctggggagt acgaccgcaa ggttgaaact 900
caaaggaatt gacgggggcc cgcacaagcg gtggagcatg tggtttaatt cgaagcaacg 960
cgaagaacct taccaggtct tgacatcttt tgatcacctg agagatcagg tttccccttc 1020
gggggcaaaa tgacaggtgg tgcatggttg tcgtcagctc gtgtcgtgag atgttgggtt 1080
aagtcccgca acgagcgcaa cccttatgac tagttgccag catttagttg ggcactctag 1140
taagactgcc ggtgacaaac cggaggaagg tggggatgac gtcaaatcat catgcccctt 1200
atgacctggg ctacacacgt gctacaatgg atggtacaac gagttgcgag accgcgaggt 1260
caagctaatc tcttaaagcc attctcagtt cggactgtag gctgcaactc gcctacacga 1320
agtcggaatc gctagtaatc gcggatcagc acgccgcggt gaatacgttc ccgggccttg 1380
tacacaccgc ccgtcacacc atgagagttt gtaacacccg aagccggtgg cgtaaccctt 1440
ttagggagcg agccgtctaa ggtgaacaaa a 1471
Claims (10)
1.一种鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01,其保藏编号为GDMCC No:60986。
2.权利要求1所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物。
3.权利要求1所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01、或权利要求2所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物在制备预防和/或治疗幽门螺杆菌感染的药物中的应用。
4.权利要求1所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01、或权利要求2所述鼠李糖乳杆菌(Lactobacillus rhamnosus)LRX-01的培养物或代谢产物在制备预防和/或治疗幽门螺杆菌感染引起的胃肠道疾病的药物中的应用。
5.根据权利要求4所述的应用,其特征在于,所述胃肠道疾病为胃溃疡、胃炎或胃癌。
6.一种预防和/或治疗幽门螺杆菌感染的产品,其特征在于,包括活性成分和辅料,所述活性成分包括权利要求1所述鼠李糖乳杆菌(Lactobacillusrhamnosus)LRX-01,或权利要求2所述鼠李糖乳杆菌(Lactobacillusrhamnosus)LRX-01的培养物或代谢产物。
7.根据权利要求6所述的产品,其特征在于,所述产品为保健品、食品、药品、菌剂或饲料添加剂。
8.根据权利要求7所述的产品,其特征在于,所述食品为乳制品、蔬菜制品、饮料制品或其他发酵类制品。
9.根据权利要求7所述的产品,其特征在于,所述保健品为液体状保健品、颗粒状保健品、粉末状保健品、胶囊状保健品或片状保健品。
10.根据权利要求7所述的产品,其特征在于,所述药品为片剂、颗粒剂、散剂、胶囊剂、溶液剂、悬浮剂、或冻干制剂。
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