CN115369047A - 一种马克斯克鲁维酵母菌株及其应用 - Google Patents
一种马克斯克鲁维酵母菌株及其应用 Download PDFInfo
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- CN115369047A CN115369047A CN202211158058.XA CN202211158058A CN115369047A CN 115369047 A CN115369047 A CN 115369047A CN 202211158058 A CN202211158058 A CN 202211158058A CN 115369047 A CN115369047 A CN 115369047A
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- kluyveromyces marxianus
- fermented milk
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Abstract
本发明公开了一种马克斯克鲁维酵母菌株及其应用,该菌株为马克斯克鲁维酵母菌株ProfMIC‑214,保藏编号为CCTCC NO:M 20221046,该马克斯克鲁维酵母菌株采用如下分离方法制得:于传统雪莲菌发酵牛奶中采样,吸取雪莲菌发酵牛奶置于装有无菌生理盐水的试管中,充分振荡使其混匀;将混合后雪莲菌发酵牛奶进行梯度稀释,吸取稀释后的样液采用涂布法均匀涂布于麦芽汁琼脂培养基上备用;将准备好的培养基置于30℃恒温培养箱中培养24~48h,挑取白色菌落反复接种筛选,直至得到均匀的单个菌落。该马克斯克鲁维酵母菌株具有促进细胞增殖、抗衰老的功能,可用于制备食品、药品、化妆品等。
Description
技术领域
本发明涉及微生物技术领域,特别涉及一种马克斯克鲁维酵母菌株及其应用。
背景技术
皮肤是机体的第一道防线,发挥着抵御外界各种侵害、维持内环境稳态及保障机体生理功能的重要作用。皮肤老化分为内外两种:一种是由于年龄的增长,体内细胞新陈代谢衰退,导致皮肤自然老化;另一种是由于外界环境因素导致的皮肤老化。其中光老化是皮肤外在老化最主要的形式,而导致皮肤光老化的主要原因就是紫外线辐射。皮肤在老化的过程中,由于紫外线导致的光老化占到80%,而自然老化仅占到20%。光老化导致ROS异常表达、MMPs、COX-2等生成并导致炎症发生,同时细胞增殖降低,细胞凋亡增加,细胞外基质成分(胶原蛋白、弹性蛋白、糖胺聚糖等)随着皮肤衰老而显着减少。此外,多种因素如线粒体损伤、炎症反应等产生的活性氧增加,同时,与年龄相关的细胞修复能力下降,使得氧化应激增加,老化受损细胞无法及时清除,从而导致了皮肤衰老。
在衰老机制的研究中发现,细胞自噬能够延缓器官功能退化,可以通过清除UV辐照细胞内受损的蛋白质和脂质,修复DNA,帮助细胞恢复代谢稳态,为光老化受损的皮肤提供保护作用。另外,减少细胞凋亡,降低细胞炎症,增加细胞外基质的合成以及减少其降解,提升细胞的抗氧化能力等都已被证实能够减缓皮肤细胞衰老。如果能够同时针对不同皮肤老化途径起到抑制作用并且提升皮肤细胞状态就能最大程度抵御衰老进程,寻求多层次多维度的抗衰老物质是目前的研究热点。
皮肤具有自我更新能力,皮肤微生物分解磷脂、固醇类、角质蛋白也可使皮肤细胞吸收并促进细胞生长、延缓衰老和减少皱纹产生。因此,提供一种利用微生态技术开发的益生菌相关产品,具有重要的现实意义。
发明内容
有鉴于此,本发明提供了一种马克斯克鲁维酵母菌株及其应用。
本发明提供了一种马克斯克鲁维酵母菌株,所述菌株为马克斯克鲁维酵母菌株ProfMIC-214(Kluyveromyces marxianus ProfMIC-214),保藏编号为CCTCC NO:M20221046,所述马克斯克鲁维酵母菌株采用如下分离方法制得:
于传统雪莲菌发酵牛奶中采样,吸取雪莲菌发酵牛奶置于装有无菌生理盐水的试管中,充分振荡使其混匀;
将混合后雪莲菌发酵牛奶进行梯度稀释,吸取稀释后的样液采用涂布法均匀涂布于麦芽汁琼脂培养基上备用;
将准备好的培养基置于25~35℃恒温培养箱中培养24~48h,挑取白色菌落反复接种筛选,直至得到均匀的单个菌落。
进一步的,上述马克斯克鲁维酵母菌株,其中,雪莲菌发酵牛奶与无菌生理盐水混合时的体积比为1:9。
本发明还公开了一种马克斯克鲁维酵母菌株在制备改善皮肤细胞状况的产品中的应用,所述产品为食品、药品或化妆品。
进一步的,上述应用,其中,所述改善皮肤状况包括促进细胞增殖和抗衰老中的至少一种。
进一步的,上述应用,其中,所述促进细胞增殖包括促进人成纤维细胞增殖。
进一步的,上述应用,其中,所述抗衰老为上调细胞外基质相关基因的表达,所述细胞外基质相关基因包括FN、LN、MKX和COL13A1中的至少一种。
进一步的,上述应用,其中,所述抗衰老为下调降解细胞外基质相关基因的表达,所述降解细胞外基质相关基因包括MMP家族中的至少一种。
进一步的,上述应用,其中,所述抗衰老为下调细胞凋亡相关基因的表达,所述细胞凋亡相关基因为BAX基因。
进一步的,上述应用,其中,所述抗衰老为上调细胞抗氧化相关基因PTEN、SIRT-1和/或SIRT-3的表达。
进一步的,上述应用,其中,所述抗衰老为上调免疫调节因子相关基因MOR的表达。
本发明还公开了一种改善皮肤状况的产品,其原料包括权利要求1或2所述的马克斯克鲁维酵母菌株。
进一步的,上述产品,其包括上述的马克斯克鲁维酵母菌株的灭活菌或灭活上清液。
本发明公开的马克斯克鲁维酵母菌株ProfMIC-214,其保藏编号为CCTCC NO:M20221046。实验表明,该马克斯克鲁维酵母菌株ProfMIC-214具有促进细胞增殖、抗衰老的功能,可用于制备食品、药品、化妆品等。
生物保藏说明
马克斯克鲁维酵母(Kluyveromyces marxianus)ProfMIC-214,于2022年7月6日保藏在中国典型培养物保藏中心,地址为:中国,武汉,武汉大学,保藏编号为CCTCC NO:M20221046。
具体实施方式
本发明提供了马克斯克鲁维酵母菌株及其应用。本领域技术人员可以借鉴本文内容,适当改进工艺参数实现。特别需要指出的是,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述,相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合,来实现和应用本发明技术。
本发明的马克斯克鲁维酵母菌株ProfMIC-214,来源于传统雪莲菌发酵牛奶,经18S rDNA鉴定为马克斯克鲁维酵母(Kluyveromyces marxianus)。菌株ProfMIC-214显微镜下呈椭圆形,大小约4-8μm,出芽生殖,单个、两个或多个系成串黏连;在麦芽汁琼脂平板上生长,可形成圆形、乳白色、边缘整齐菌落;在麦芽汁液体培养基中呈均匀浑浊生长,久置菌体呈白色沉淀,最适生长温度30℃。
马克斯克鲁维酵母菌株(Kluyveromyces marxianus)ProfMIC-214,保藏单位:中国典型培养物保藏中心,地址:湖北省武汉市武昌区八一路299号武汉大学校内,保藏日期:2022年7月6日,保藏编号为CCTCC NO:M 20221046。
进一步,本发明提供的马克斯克鲁维酵母菌株ProfMIC-214在本发明所述的应用或产品中,存在形式是活的或死的或经间歇灭菌的,或为裂解物和/或提取物的形式,或为细菌产物的形式或为上清液形式或衍生物形式,所述衍生物形式优选地选自:代谢产物、代谢生物产物、外泌体、益生素、细胞壁及其成分、胞外多糖,和含有免疫原性成分的化合物,优选地选自:上清液、灭活菌体。
体外细胞实验表明,本发明的马克斯克鲁维酵母菌株ProfMIC-214具有促进人成纤维细胞HFF增殖的作用,增殖率108.89%~124.72%。
体外细胞实验表明,本发明的马克斯克鲁维酵母菌株ProfMIC-214具有上调HFF细胞外基质相关的层粘连蛋白LN、纤维连接蛋白基因FN、莫霍克蛋白基因MKX和XIII型胶原α1链基因COL13A1,免疫调节因子相关的β-内啡肽受体基因MOR,抗氧化相关的10号染色体缺失的磷酸酶及张力蛋白同源物基因PTEN以及Sirtuins蛋白家族基因SIRT-1和SIRT-3表达的作用,基因相对表达倍数1.03~1.98倍;具有下调降解细胞外基质相关的基质金属蛋白酶家族基因MMP和细胞凋亡相关的BCL2-Associated X蛋白基因BAX,基因相对表达倍数0.75~0.82。
本发明采用的试材皆为普通市售品,均可市售购买得到,下面结合实施例,进一步阐述本发明:
实施例1ProfMIC-214的分离
于传统雪莲菌发酵牛奶中采样。吸取1mL雪莲菌发酵牛奶置于装有9mL无菌生理盐水的试管中,充分振荡使其混匀。将混合后雪莲菌发酵牛奶进行梯度稀释,吸取1mL样液采用涂布法均匀涂布于麦芽汁琼脂培养基上,将制备好的平板置于30℃恒温培养箱中培养24~48h,挑取白色菌落反复接种筛选,直至得到均匀的单个菌落,得到马克斯克鲁维酵母菌株ProfMIC-214。
镜检:菌株ProfMIC-214显微镜下呈椭圆形,大小约4-8μm,出芽生殖,单个、两个或多个系成串黏连;在麦芽汁琼脂平板上生长,可形成圆形、乳白色、边缘整齐菌落;在麦芽汁液体培养基中呈均匀浑浊生长,久置菌体呈白色沉淀。
实施例2ProfMIC-214的核酸鉴定
1、18S rDNA基因序列分析:
挑取单菌落置麦芽汁液体培养基中,30℃培养过夜后,12000转离心1min收集菌体,按照DNA提取试剂盒步骤进行操作。引物采用酵母菌通用引物NS1,NS8,PCR扩增体系为50μL体系,95℃预变性5min;94℃1min,52℃1min,72℃1.5min,36个循环;72℃延伸10min。
2、结果
PCR产物测序结果与GenBank中已发表的标准序列进行同源性比较(BLASTN)后得出ProfMIC-214菌株为马克斯克鲁维酵母(Kluyveromyces marxianus)。
实施例3ProfMIC-214促进人成纤维细胞HFF的增殖
1、ProfMIC-214上清液的制备:
挑取马克斯克鲁维酵母菌株ProfMIC-214单菌落于马铃薯葡萄糖液体培养基,置于摇床30℃、160r/min培养12-16h,酶标仪检测并以PBS稀释调整OD600=0.2,121℃,30min高压灭活,12000转离心2min,经0.22μm滤膜过滤为上清液。
2、HFF细胞制备及ProfMIC-214添加
接种以DMEM培养的HFF细胞,以100ul/孔(每孔含3×104细胞)转接至96孔板,过夜培养至细胞贴壁。配制200μM H2O2,每孔加入100μl,5%二氧化碳培养箱37℃培养1h。弃掉原培养基,PBS清洗两次,加入100μl新培养基,各孔分别添加ProfMIC-214上清液5%(V/V)(对照组分别以等体积PBS替代上清液),培养24h。向每孔加入10μl的CCK-8溶液,培养4h,检测450nm处吸亮度A。计算公式为:细胞增殖率=实验组A/对照组A*100%。计算结果如表1所示。
表1 ProfMIC-214促进HFF细胞增殖
结果显示添加ProfMIC-214具有促进HFF细胞增殖的作用。
实施例4ProfMIC-214调节氧化损伤HFF细胞外基质/细胞凋亡/抗氧化/免疫调节因子相关基因表达实验
1、ProfMIC-214上清液及灭活菌体制备:
挑取马克斯克鲁维酵母菌株ProfMIC-214单菌落于马铃薯葡萄糖液体培养基,置于摇床30℃、160r/min培养12-16h,酶标仪检测并以PBS稀释调整OD600=0.2,121℃,30min高压灭活,12000转离心2min,经0.22μm滤膜过滤为上清液。离心沉淀以适量PBS重悬,稀释调整OD600=0.2,为灭活菌体。
2、HFF细胞制备及H2O2诱导氧化损伤
将DMEM培养的HFF细胞消化后以0.5ml/孔(内含2×105细胞)接种至24孔板,5%二氧化碳培养箱37℃培养过夜。每孔加入终浓度为200μM的H2O2进行刺激,37℃静置1h。
3、ProfMIC-214添加
将上清液5%(V/V)、灭活菌体10%(V/V)分别加入刺激过的HFF细胞(对照组分别以等体积PBS替代上清液/灭活菌体)。每组3平行,37℃培养过夜。
4、qPCR法检测细胞外基质/细胞凋亡/抗氧化/免疫调节因子相关基因相对表达倍数
将上述细胞弃去培养基后,加入裂解液,提取细胞总RNA,检测RNA浓度及纯度后反转录为cDNA,以GAPDH为内参基因,采用实时qPCR检测细胞外基质相关基因FN、LN、MKX和COL13A1,抗氧化相关基因PTEN、SIRT-1和SIRT-3,免疫调节因子相关基因MOR;以及降解细胞外基质相关基因MMP家族,细胞凋亡相关基因BAX的表达。以对照组基因相对表达倍数F=1,利用2-ΔΔCT法计算各样品F值。
上清液上调细胞外基质相关基因FN、MKX和COL13A1,抗氧化相关基因PTEN,免疫调节因子相关基因MOR;下调降解细胞外基质相关基因MMP10,细胞凋亡相关基因BAX,结果如表2所示。
表2 ProfMIC-214上清液调节细胞外基质/细胞凋亡/抗氧化/免疫调节因子相关基因的表达
灭活菌体上调抑制细胞外基质相关基因LN、FN、MKX和COL13A1,抗氧化相关基因PTEN、SIRT-1和SIRT-3,免疫调节因子相关基因MOR;下调降解细胞外基质相关基因MMP3。结果如表3所示。
表3 ProfMIC-214灭活菌体调节细胞外基质/抗氧化/免疫调节因子相关基因的表达
结果显示加入ProfMIC-214具有促进HFF细胞外基质合成、减少细胞凋亡、增加抗氧化、增加细胞免疫调节因子、减少细胞外基质降解的抗衰老作用。
实施例5 ProfMIC-214上清液冲剂制备实例
ProfMIC-214上清液冲剂的制备,组方如表4所示。
表4
原料 | 质量比例(%) |
ProfMIC-214发酵粉 | 50 |
鱼胶原蛋白 | 30 |
柑橘果汁粉 | 18.8 |
维生素C | 0.8 |
二氧化硅 | 0.4 |
制备工艺:取实施例4制备的ProfMIC-214上清液,喷雾干燥后制成ProfMIC-214发酵粉,加入鱼胶原蛋白、维生素C、柑橘果汁粉、二氧化硅,搅拌分散均匀即完成冲剂。所得ProfMIC-214冲剂以水冲泡后味道酸甜,适口性佳,携带方便,可做为皮肤保养的口服饮品。
实施例6ProfMIC-214灭活菌体精华水制备实例
ProfMIC-214灭活菌体精华水的制备,组方如表5所示。
表5
原料 | 质量比例(%) |
ProfMIC-214灭活菌体液 | 70 |
甘油 | 19.5 |
1,3-丁二醇 | 10 |
苯氧乙醇 | 0.4 |
香兰素 | 0.1 |
制备工艺:取实施例4制备的ProfMIC-214灭活菌体液,加热至50℃,加入甘油、1,3-丁二醇、苯氧乙醇、香兰素,搅拌分散均匀直至清澈,冷却至35℃即完成。所得ProfMIC-214灭活菌体精华水气味清新,使用前摇晃以重悬菌体,涂抹肤感润滑不粘腻感。
在本说明书的描述中,参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不一定指的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
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本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。
Claims (11)
1.一种马克斯克鲁维酵母菌株,其特征在于,所述菌株为马克斯克鲁维酵母菌株ProfMIC-214,保藏编号为CCTCC NO:M 20221046,所述马克斯克鲁维酵母菌株采用如下分离方法制得:
于传统雪莲菌发酵牛奶中采样,吸取雪莲菌发酵牛奶置于装有无菌生理盐水的试管中,充分振荡使其混匀;
将混合后雪莲菌发酵牛奶进行梯度稀释,吸取稀释后的样液采用涂布法均匀涂布于麦芽汁琼脂培养基上备用;
将准备好的培养基置于30℃恒温培养箱中培养24~48h,挑取白色菌落反复接种筛选,直至得到均匀的单个菌落。
2.权利要求1所述的马克斯克鲁维酵母菌株在制备改善皮肤细胞状况的产品中的应用,所述产品为食品、药品或化妆品。
3.根据权利要求2所述的应用,其特征在于,所述改善皮肤状况包括促进细胞增殖和抗衰老中的至少一种。
4.根据权利要求3所述的应用,其特征在于,所述促进细胞增殖包括促进人成纤维细胞增殖。
5.根据权利要求3所述的应用,其特征在于,所述抗衰老为上调细胞外基质相关基因的表达,所述细胞外基质相关基因包括FN、LN、MKX和COL13A1中的至少一种。
6.根据权利要求3所述的应用,其特征在于,所述抗衰老为下调降解细胞外基质相关基因的表达,所述降解细胞外基质相关基因包括MMP家族中的至少一种。
7.根据权利要求3所述的应用,其特征在于,所述抗衰老为下调细胞凋亡相关基因的表达,所述细胞凋亡相关基因为BAX基因。
8.根据权利要求3所述的应用,其特征在于,所述抗衰老为上调细胞抗氧化相关基因PTEN、SIRT-1和/或SIRT-3的表达。
9.根据权利要求3所述的应用,其特征在于,所述抗衰老为上调免疫调节因子相关基因MOR的表达。
10.一种改善皮肤状况的产品,其特征在于,其原料包括权利要求1所述的马克斯克鲁维酵母菌株。
11.根据权利要求10所述的产品,其特征在于,包括权利要求1所述的马克斯克鲁维酵母菌株的灭活菌或灭活上清液。
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