CN113143972B - 嗜热链球菌timr0705-6在制备抗高尿酸血症和抗痛风药物中的应用 - Google Patents
嗜热链球菌timr0705-6在制备抗高尿酸血症和抗痛风药物中的应用 Download PDFInfo
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- CN113143972B CN113143972B CN202110545826.6A CN202110545826A CN113143972B CN 113143972 B CN113143972 B CN 113143972B CN 202110545826 A CN202110545826 A CN 202110545826A CN 113143972 B CN113143972 B CN 113143972B
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Abstract
嗜热链球菌(S.thermophilus)TIMR0705‑6在制备抗高尿酸血症和抗痛风药物中的应用,属于功能性食品微生物领域。本发明以嗜热链球菌(S.thermophilus)TIMR0705‑6为研究对象,采用氧嗪酸钾联用腺嘌呤建立高尿酸血症大鼠模型,连续28天灌胃给予嗜热链球菌TIMR0705‑6株,探讨嗜热链球菌TIMR0705‑6株对高尿酸血症模型大鼠的治疗作用。研究结果显示,嗜热链球菌TIMR0705‑6株可以显著降低高尿酸血症模型大鼠的血尿酸水平,降低肾脏URAT1、GLUT9蛋白表达,提高肾脏OAT1蛋白表达,对高尿酸血症或痛风具有预防和治疗作用。
Description
技术领域
本发明属于功能性食品微生物技术领域,具体涉及一种嗜热链球菌TIMR0705-6(Streptococcus thermophilus)在制备抗高尿酸血症和抗痛风药物中的应用。
背景技术
高尿酸血症(HUA)是由于血尿酸(SUA)产生过多或排泄不足而导致的一种嘌呤代谢性疾病,可诱发痛风,并与高血压、脑梗死、肾脏损害等疾病关系密切。人体60%~70%尿酸经肾脏排泄,现代研究已证实,尿酸盐转运体(1URAT1)、葡萄糖转运体9(GLUT9)、三磷酸腺苷结合盒转运蛋白G2(ABCG2)、有机阴离子1(OAT1)、有机阴离子3(OAT3)参与尿酸重吸收和分泌过程。促进尿酸排泄是治疗HUA及预防痛风的主要方法,目前临床上促进尿酸盐排泄的主要药物苯溴马隆等,效果较明显,但存在胃肠道不适、易造成肝功能损害等不良反应。
乳酸菌作为一种安全的食品级微生物,在预防和治疗代谢调控类疾病中发挥重要作用,如改善肠道功能、降血脂、降胆固醇、抗动脉粥样硬化、降血糖等。最新研究发现,乳酸菌具有体外降解嘌呤核苷酸和动物体内降尿酸作用。但关于益生菌降尿酸和抗痛风的作用机制研究应用还不深入。
发明内容
本发明的目的是提供一种嗜热链球菌TIMR0705-6(Streptococcusthermophilus)在制备抗高尿酸血症和抗痛风药物中的应用。
本发明为解决技术问题所采用的技术方案如下:
本发明的嗜热链球菌TIMR0705-6在制备抗高尿酸血症和抗痛风药物中的应用。
作为优选的实施方式,将嗜热链球菌TIMR0705-6制成发酵剂,其浓度为108~1011CFU/g。
作为优选的实施方式,所述嗜热链球菌TIMR0705-6发酵剂的制备方法为:
将嗜热链球菌TIMR0705-6扩大培养到2L,6000r/min离心5min,生理盐水重悬,再次6000r/min离心5min,生理盐水重悬、洗净,再次6000r/min离心5min,收集菌泥,溶于1L冻干保护剂中,冻干得到嗜热链球菌TIMR0705-6发酵剂,菌数为108~1011CFU/g。
作为优选的实施方式,所述冻干保护剂为:将40g葡萄糖、5g抗坏血酸钠、80g低聚果糖、30g海藻糖溶于三级水中,定容至750mL所得。
本发明的一种具有抗高尿酸血症和抗痛风作用的菌剂,该菌剂的活性成分为嗜热链球菌TIMR0705-6。
作为优选的实施方式,将嗜热链球菌TIMR0705-6制成发酵剂,其浓度为108~1011CFU/g。
作为优选的实施方式,所述嗜热链球菌TIMR0705-6发酵剂的制备方法为:
将嗜热链球菌TIMR0705-6扩大培养到2L,6000r/min离心5min,生理盐水重悬,再次6000r/min离心5min,生理盐水重悬、洗净,再次6000r/min离心5min,收集菌泥,溶于1L冻干保护剂中,冻干得到嗜热链球菌TIMR0705-6发酵剂,菌数为108~1011CFU/g。
作为优选的实施方式,所述冻干保护剂为:将40g葡萄糖、5g抗坏血酸钠、80g低聚果糖、30g海藻糖溶于三级水中,定容至750mL所得。
作为优选的实施方式,该菌剂的功能包括(a1)至(a3)中的至少一项:
(a1)显著降低血清中尿酸水平;
(a2)降低肾脏URAT1、GLUT9蛋白表达;
(a3)提高肾脏OAT1蛋白表达。
作为优选的实施方式,该菌剂为采用冷冻干燥法制备而成的粉剂。
本发明的有益效果是:
本发明以嗜热链球菌(S.thermophilus)TIMR0705-6为研究对象,采用氧嗪酸钾联用腺嘌呤建立高尿酸血症大鼠模型,连续28天灌胃给予嗜热链球菌(S.thermophilus)TIMR0705-6株,探讨嗜热链球菌(S.thermophilus)TIMR0705-6株对高尿酸血症模型大鼠的治疗作用。研究结果显示,嗜热链球菌(S.thermophilus)TIMR0705-6株可以显著降低高尿酸血症模型大鼠的血尿酸水平,降低肾脏URAT1、GLUT9蛋白表达,提高肾脏OAT1蛋白表达,对高尿酸血症或痛风具有预防和治疗作用。
以日常摄入嗜热链球菌(S.thermophilus)TIMR0705-6株或其菌剂,具有明显的抗高尿酸血症作用,机制与抑制大鼠肾脏URAT1、GLUT9蛋白表达而减少尿酸的重吸收、上调肾脏OAT1蛋白表达而促进尿酸的分泌有关。因此,本发明可为运用该菌株治疗高尿酸血症和痛风提供依据,为嗜热链球菌(S.thermophilus)TIMR0705-6株可以用于制备抗高尿酸血症或抗痛风功能的食品、药品或保健品等开发提供基础。
附图说明
图1为实施例1中嗜热链球菌TIMR0705-6(S.thermophilus)对高尿酸血症模型大鼠肾组织中GLUT9、OAT1、URAT1蛋白表达的影响。
具体实施方式
本发明提供一种嗜热链球菌TIMR0705-6(S.thermophilus)在制备抗高尿酸血症和抗痛风产品中的应用。其产品可以为食品、保健品或药品。
其中,该嗜热链球菌TIMR0705-6(S.thermophilus)为现有技术,其制备方法和性能参数等信息参见公开号为CN102965318A,公开日为2013.03.13,名称为一株产胞外多糖的嗜热链球菌及其应用的中国专利。
优选的,将嗜热链球菌TIMR0705-6(S.thermophilus)制成发酵剂,其浓度为108~1011CFU/g。
优选的,嗜热链球菌TIMR0705-6(S.thermophilus)发酵剂的制备方法为:
将嗜热链球菌TIMR0705-6(S.thermophilus)扩大培养到2L,6000r/min离心5min,生理盐水重悬,再次6000r/min离心5min,生理盐水重悬、洗净,再次6000r/min离心5min,收集菌泥,溶于1L冻干保护剂中,冻干得到嗜热链球菌TIMR0705-6(S.thermophilus)发酵剂,菌数为108~1011CFU/g。
优选的,所说的冻干保护剂为:将40g葡萄糖、5g抗坏血酸钠、80g低聚果糖、30g海藻糖溶于三级水中,定容至750mL所得。
本发明的一种具有抗高尿酸血症和抗痛风作用的菌剂,该菌剂的活性成分为嗜热链球菌TIMR0705-6(S.thermophilus)。
其中,该菌剂的功能包括(a1)至(a3)中的至少一项:
(a1)显著降低血清中尿酸水平;
(a2)降低肾脏URAT1、GLUT9蛋白表达;
(a3)提高肾脏OAT1蛋白表达。
优选的,该菌剂可以为采用冷冻干燥法制备而成的粉剂。
下面将结合本发明实施例,对本发明实施例中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。
以下实施例中所用到的试验材料,如无特殊说明,均购自常规生化试剂公司。以下实施例中的定量试验,均设置三次重复实验,结果取平均值。
实验材料:
SD大鼠(体重180~220g):购自长春市亿斯实验动物技术有限责任公司。
基础饲料:购自长春市亿斯实验动物技术有限责任公司。
固体LAMVAB培养基:溶液A:MRS基础培养基104.4g/L,半胱氨酸盐酸盐0.5g/L,溴甲酚绿0.05g/L,4M盐酸调pH为5.0;溶液B:琼脂40g/L;溶液C:盐酸万古霉素2mg/mL4℃保存。将A、B溶液121℃,15min灭菌,C溶液0.22μm滤膜过滤。
固体MRS培养基:溶剂为水,含蛋白胨10g/L、牛肉膏10g/L、酵母膏5g/L、KH2PO42g/L、乙酸钠5g/L、柠檬酸钠5g/L、MgSO4·7H2O0.2g/L、MnSO4·4H2O0.05g/L、吐温-801mL/L、琼脂15g/L、葡萄糖20g/L;pH6.6。
液体MRS培养基与固体MRS培养基的区别仅在于不加入琼脂。
别嘌呤醇片(100mg/粒),购自广州彼迪药业有限公司,批号:20200602;氧嗪酸钾,山东济南诚汇双达化工有限公司(进口分装)批号:20022301,配制方法:每次准确称取15g以蒸馏水配成15%的混悬乳液;腺嘌呤,广州市齐云生物技术有限公司,批号:20200710;采用南京建成尿酸检测试剂盒检测血清中的尿酸含量;GAPDH、URAT1、GLUT9、OAT1一抗,羊抗兔IgG二抗均购自美国Abcam公司。
实施例1嗜热链球菌(S.thermophilus)TIMR0705-6对氧嗪酸钾联用腺嘌呤致大鼠高尿酸血症的影响
本实施例采用动物体内模型,并通过蛋白杂交技术,探讨嗜热链球菌降尿酸、抗痛风的作用机制,为寻找预防和缓解痛风的新策略奠定基础。
1、动物模型的建立及分组
40只雄性SD大鼠,随机分成4组,每组10只,分组处理如下:模型组、别嘌醇组和TIMR0705-6组连续28天按腺嘌呤100mg/kg+氧氰酸钾1.5g/kg灌胃建立高尿酸血症大鼠模型;对照组灌胃等剂量灭菌生理盐水。造模药物给药后4h,TIMR0705-6组灌胃浓度为1.0×109CFU/mL的嗜热链球菌TIMR0705-6菌液2mL,对照组和模型组灌胃等剂量灭菌生理盐水。试验结束后,取各组大鼠心脏取血,3000r/min离心15min,收集血清。
2、血清尿酸检测
于给药14d给药后1h眼眶静脉丛采血;给药28d末次给药后1h,腹腔注射戊巴比妥钠(45mg/kg)麻醉,大鼠腹主动脉取血,分离血清检测尿酸(UA)水平。
表1嗜热链球菌TIMR0705-6对高尿酸血症模型大鼠血尿酸的影响
注:同对照组相比,##p<0.01;同模型组相比,**p<0.01,*p<0.05。
结果如表1所示,嗜热链球菌TIMR0705-6具有明显降低高尿酸血症模型大鼠血尿酸含量的作用。造模后与正常对照组比较,模型组大鼠血清UA水平显著升高(P<0.05);与模型组比较,TIMR0705-6组大鼠血清UA水平在给药14d至28d逐渐降低。
3、嗜热链球菌TIMR0705-6对高尿酸血症模型大鼠肾组织URAT1、GLUT9、OAT1蛋白表达水平的影响
取20mg大鼠肾组织,加入200μL裂解液混合匀浆,4℃、12000×g离心15min,取上清,采用BCA法进行蛋白定量。取20μg蛋白样品,经12%SDS-PAGE分离,浓缩胶电泳电压为80V,分离胶电泳电压为120V,电泳结束后采用湿转法将蛋白转移至0.22μmPVDF膜上,加入5%脱脂奶粉于4℃封闭过夜,分别加入GLUT9、OAT1、URAT1抗体(1:1000),室温孵育1h,PBST洗涤3次,5min/次。加入经辣根过氧化物酶标记的山羊抗兔IgG,室温孵育1h,PBST洗涤3次,5min/次。加入化学发光试剂,暗室曝光,用TANONGIS软件读取条带灰度值。
结果如图1所示,与正常对照组比较,模型组大鼠肾组织URAT1、GLUT9蛋白表达显著升高,OAT1蛋白表达显著降低(P<0.05)。与模型组比较,嗜热链球菌TIMR0705-6组大鼠肾组织URAT1、GLUT9蛋白表达显著降低,OAT1蛋白表达显著升高(P<0.05)。
综上所述,以日常摄入嗜热链球菌(S.thermophilus)TIMR0705-6株或其菌剂代替抗痛风药物,可明显降低氧嗪酸钾联用腺嘌呤致高尿酸血症模型大鼠的血清尿酸,降低肾脏URAT1、GLUT9蛋白表达,提高肾脏OAT1蛋白表达,因此,嗜热链球菌(S.thermophilus)TIMR0705-6株对高尿酸血症和痛风具有良好的预防和治疗作用。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (4)
1.嗜热链球菌TIMR0705-6在制备抗高尿酸血症和抗痛风药物中的应用,其特征在于,所述药物的活性成分为嗜热链球菌TIMR0705-6的菌剂。
2.根据权利要求1所述的应用,其特征在于,将嗜热链球菌TIMR0705-6制成发酵剂,其浓度为108~1011CFU/g。
3.根据权利要求2所述的应用,其特征在于,所述嗜热链球菌TIMR0705-6发酵剂的制备方法为:
将嗜热链球菌TIMR0705-6扩大培养到2L,6000r/min离心5min,生理盐水重悬,再次6000r/min离心5min,生理盐水重悬、洗净,再次6000r/min离心5min,收集菌泥,溶于1L冻干保护剂中,冻干得到嗜热链球菌TIMR0705-6发酵剂,菌数为108~1011CFU/g。
4.根据权利要求3所述的应用,其特征在于,所述冻干保护剂为:将40g葡萄糖、5g抗坏血酸钠、80g低聚果糖、30g海藻糖溶于三级水中,定容至750mL所得。
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