CN117045686A - 解纤维素拟杆菌在制备药物中的应用 - Google Patents
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Abstract
本发明公开了解纤维素拟杆菌在制备药物中应用,特别是该药物用于防治胰岛素抵抗或因胰岛素抵抗引起的2型糖尿病,该药物可以为生物药品。本发明所述的解纤维拟杆菌可显著降低高脂饮食诱导的体重增加、改善糖耐量、促进胰岛素分泌、改善胰岛素抵抗,并且能明显提高免疫力和改善炎症。本发明提供的解纤维素拟杆菌能够有效缓解胰岛素抵抗症状、防治胰岛素抵抗引起的2型糖尿病,且未发现明显的不良反应,安全性好,具有广阔的前景。
Description
技术领域
本发明属于生物医药领域,具体的说,涉及解纤维素拟杆菌在制备用于防治胰岛素抵抗或因胰岛素抵抗引起的2型糖尿病的药物中的应用。
背景技术
胰岛素是由胰岛β细胞在内源性或外源性物质的刺激下而分泌的一种蛋白质激素,其主要生理功能是调节机体的糖脂代谢,并促进蛋白质合成,胰岛素靶器官或组织在机体中分布较广,如肌肉、脂肪、肝脏乃至肾脏等。当这些胰岛素靶器官或组织对内源性或外源性胰岛素的敏感性和反应性降低时就会发生全身或局部的胰岛素抵抗。胰岛素抵抗在临床上极为常见。胰岛素抵抗不仅是胰岛素抵抗是导致诸多代谢紊乱(如心血管疾病、脂肪肝、多囊卵巢综合征等)的共同土壤,还是一些少见病和罕见病的病理生理学基础。胰岛素抵抗是2型糖尿病发生的主要诱因之一,大部分的2型糖尿病人存在胰岛素抵抗。而且在糖尿病的治疗过程中,如果不能很好地解决胰岛素抵抗问题,还会影响血糖的控制效果。同时目前大量临床证据表明存在胰岛素抵抗或患有2型糖尿病的人群伴有体重增加、慢性炎症与免疫应答紊乱等。因此通过恢复糖耐量受损、降低体重、抗炎、调节免疫等能改善治疗胰岛素抵抗症状,可为因胰岛素抵抗引起的2型糖尿病的防治提供解决方案。
随着对微生物群的了解逐渐深入,很多研究表明,肠道微生物在宿主的代谢和疾病状态中起着重要的作用,其中,肠道菌群的生态失调导致胰岛素抵抗和2型糖尿病,同时肠道菌群调节也成为了改善胰岛素抵抗和治疗2型糖尿病的关键手段。目前在糖尿病的药物治疗方面,除可施予胰岛素外,主要目的是使不足的胰岛素上升、调降进食后的高血糖和改善胰岛素抗阻性等,但同时存在着不良反应及副作用,如服用α-葡萄糖苷酶抑制剂可能出现腹胀或偶尔腹泻、腹痛及呕心;双胍类药物在初服可能有肠胃道的不适,如厌食,恶心、呕吐或腹泻等,少数人可能出现皮疹,且长期使用后均可能会有失活的现象发生;磺脲类药物最常见的副作用是低血糖及体重增加等。随着对肠道菌群研究的深入,肠道菌作为药物对疾病进行干预和治疗受到了广泛的关注。首先,肠道菌可以直接到达胃肠道,例如直接调节肠道菌群,或改变酶活性。其次,可直接与肠道黏液层和上皮细胞相互作用,从而影响肠道屏障功能和黏膜免疫系统。第三,可以在胃肠道外发挥作用,例如对全身免疫系统和其他器官发挥作用,如肝脏和大脑。同时不会产生抗药性,可以更好的保证人体的健康,预防疾病的产生。解纤维素拟杆菌在肥胖人群中丰度降低(Alternation of the gut microbiotain metabolically healthy obesity: An integrated multiomics analysis. Front Cell Infect Microbiol. 2022;12:1012028),并且具有抗炎及调节免疫的作用(Disruption of Genes Encoding Putative Zwitterionic Capsular Polysaccharidesof Diverse Intestinal Bacteroides Reduces the Induction of Host Anti-Inflammatory Factors. Microb Ecol. 2023;85(4):1620-1629.),但目前尚不清楚解纤维素拟杆菌是否具有缓解胰岛素抵抗的生物学功能。
因鉴于此,特提出此发明。
发明内容
本发明目的在于提供解纤维素拟杆菌在制备用于防治胰岛素抵抗的药物中的应用。
为实现上述目的,采用以下技术方案:
本发明提供了一种解纤维素拟杆菌在制备药物中应用,所述药物用于防治胰岛素抵抗或因胰岛素抵抗引起的2型糖尿病。
优选的,如上所述的应用,所述解纤维素拟杆菌为Bacteroidescellulosilyticus DSM14838。
一方面,本发明还提供了一种药物,所述药物用于防治胰岛素抵抗或因胰岛素抵抗引起的2型糖尿病,所述药物包含解纤维素拟杆菌,所述解纤维素拟杆菌是其中的活性成分。
优选的,所述解纤维素拟杆菌是解纤维素拟杆菌(Bacteroides cellulosilyticus),其保藏编号为DSM14838。
可选的,本文所述药物是生物药品。
可选的,本文所述药物中所述解纤维素拟杆菌是唯一的活性成分;可选的,所述药物是药物组合物,其中所述解纤维素拟杆菌是其中的活性成分之一。
如上所述的应用,本文所述药物以解纤维素拟杆菌作为主要活性成分。
优选的,本文所述药物含有1×105-1×1014CFU/mL或1×105-1×1014CFU/g的解纤维素拟杆菌。
可选的,本文所述药物还包括药学上可接受的载体,该药学载体选自乳糖、葡萄糖、蔗糖、山梨糖醇、甘露糖、海藻糖、淀粉、阿拉伯胶、磷酸钙、藻酸盐、明胶、硅酸钙、细结晶纤维素、聚乙烯吡咯烷酮、纤维素、水、糖浆、甲基纤维素、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁及矿物油中的至少一种。
优选的,本文所述2型糖尿病是由所述胰岛素抵抗症状引发的。
优选的,本文所述胰岛素抵抗症状是由高脂饮食引起的。
进一步的,如上所述的应用还包括改善体重增加、糖耐量异常、免疫力降低、炎症等症状的一种或两种以上。进一步的,上述症状是由于高脂饮食引起的。
进一步的,所述改善免疫力降低是指增加个体的血清免疫球蛋白A、免疫球蛋白M和免疫球蛋白G;
进一步的,所述改善炎症是指降低高脂饮食个体的促炎因子浓度和增加其抗炎因子浓度。在一个具体实施方式中,所述改善炎症是指降低高脂饮食个体的C反应蛋白分泌和促进白介素10的合成与分泌。
可选的,本文所述药物是液体制剂或固体制剂。
可选的,本文所述药物为口服药物。可选的,所述药物基于胃肠道给药。
可选的,所述胃肠道给药可以在食管、胃、小肠、结肠、直肠等部位给药。
可选的,本文所述药物为散剂、片剂、颗粒剂、胶囊剂、溶液剂、乳剂、混悬剂等。例如在一个具体实施方式中,所述药物为溶液剂,通过灌胃的方式给药;在一些实施方式中,所述药物为胶囊剂,通过口服给药;在一些实施方式中,所述药物为溶液剂或混悬剂,通过小肠、结肠或直肠给药。
本发明的有益效果为:
本发明所述的解纤维素拟杆菌可显著降低高脂饮食诱导的体重增加,改善糖耐量,促进胰岛素分泌、改善胰岛素抵抗,并且能显著提高免疫力、改善炎症。本发明提供的解纤维素拟杆菌能够有效防治胰岛素抵抗,且未发现明显的不良反应,安全性好,具有广阔的前景。
附图说明
图1是小鼠的体重监测曲线;
图2是干预4周后小鼠的体重;
图3是干预4周后小鼠口服葡萄糖耐量试验(OGTT)结果图;
图4是干预4周后小鼠口服葡萄糖耐量试验的曲线下面积(AUC);
图5是干预4周后小鼠胰岛素耐量试验(ITT)结果图;
图6是干预4周后小鼠胰岛素耐量试验的曲线下面积(AUC);
图7是干预4周后小鼠空腹胰岛素水平;
图8是干预4周后小鼠空腹葡萄糖浓度;
图9是干预4周后小鼠肝脏、肾脏组织HE染色代表性图片;
其中,HFD Model、HFD + BC分别表示高脂饮食、高脂饮食+解纤维素拟杆菌,每组10只小鼠,图1-8中*P < 0.05、**P < 0.01、***P < 0.001表示两组间相比差异具有统计学意义。
具体实施方式
为了更清楚阐述本申请的解纤维素拟杆菌的应用效果和作用,申请人以高脂饲料喂养的胰岛素抵抗小鼠模型为研究对象,在高脂喂养4周后给予解纤维素拟杆菌干预4周,研究小鼠体重、胰岛素抵抗、炎症及机体免疫的变化。结果显示:解纤维素拟杆菌干预后,能够改善高脂饮食所引起的小鼠口服葡萄糖耐量受损及胰岛素抵抗现象,同时在该菌干预后小鼠体重降低。采用本申请的方案,申请人还研究了上述小鼠在解纤维素拟杆菌干预后的炎症因子和免疫球蛋白水平。结果解纤维素拟杆菌干预小鼠较高脂模型组血液中C反应蛋白(CRP)、白介素1β(IL-1β)、白介素6(IL-6)及肿瘤坏死因子α(TNF-α)含量显著降低、白介素10(IL-10)、免疫球蛋白A、免疫球蛋白M及免疫球蛋白G水平显著升高。说明解纤维素拟杆菌能够改善高脂喂养引起的小鼠口服葡萄糖耐量受损和胰岛素抵抗,同时能够改善小鼠肥胖、抗炎并提高免疫力。
上述研究中,解纤维素拟杆菌干预未出现明显的不良反应,具体表现未肝肾功能指标无异常、无肝肾病理损伤。
为验证上述结果的准确性,下面对具体实验过程中的结果和数据进行介绍和分析。为了清楚、明确将实验测试中所使用的药物和试剂予以介绍,表1给出了不同试剂的名称、货号及生产制作方信息。
表1:实施例选用的主要材料及来源
实施例1:灌胃用解纤维素拟杆菌菌液的制备
称取羧甲基纤维素钠(CMC)液体培养基41.5g于1L蒸馏水或去离子水中(可按比例增加或减少配制量),加热煮沸至完全溶解,分装,121℃高压灭菌15分钟,备用。
从冻存于-80℃冰箱中取出由甘油保存的菌种37℃水浴中解冻。在厌氧手套箱内无菌操作下接种解纤维素拟杆菌菌液于CMC培养基打开甘油管,用无菌滴管将菌种转移到新配制的培养基上进行培养,于厌氧培养箱中以37℃培养。
实施例 2:解纤维素拟杆菌降低高脂饮食引起的小鼠体重增加
4-5周龄的30只雄性C57BL/6J小鼠[实验动物许可证号:SCXK(京)2019-0010]购自斯贝福(北京)生物技术有限公司。饲养条件:无特定病原体Specific Pathogen Free(SPF)级洁净度,室温20℃-22℃,湿度60 ± 5%,12小时明暗交替,自由饮食饮水。本实验中所有动物方案经北京郎克动物伦理委员会批准,并在实验动物保护协会规定的指导下进行动物实验操作。
小鼠以基础饲料适应性喂养7天后称重,随机分组,将小鼠分为正常对照组(NCDControl)、高脂模型组(HFD Model)、高脂+解纤维素拟杆菌组(HFD + BC),每组10只小鼠,NCD Control组继续基础饲料喂养,HFD Model组和HFD + BC组均以高脂饲料喂养,4周后HFD + BC组每日灌胃解纤维素拟杆菌菌液(即1×108 CFU/d解纤维素拟杆菌)4周,实验周期共8周,期间每周监测小鼠体重。
结果如图1、图2所示,与NCD Control组相比,前4周HFD Model组和HFD + BC组小鼠因高脂饮食喂养体重增长速度快,HFD + BC组经解纤维素拟杆菌干预后体重增长速度明显低于HFD Model组,干预4周后,HFD + BC组小鼠体重显著低于HFD Model组(P < 0.05),表明解纤维素拟杆菌干预后能够显著降低HFD诱导的体重增加。
实施例3:解纤维素拟杆菌能够改善高脂饮食引起的小鼠糖耐量异常与胰岛素抵抗
第8周时进行口服葡萄糖耐量试验(OGTT)考察解纤维素拟杆菌对小鼠的糖耐量的影响。各组小鼠禁食不禁水12小时,称重、尾部滴血测量空腹血糖值(葡萄糖负荷之前),按照2.0 g/kg的剂量灌胃给予小鼠20%的葡萄糖溶液,于30、60、90和120 min(葡萄糖负荷之后),取小鼠尾尖血经血糖试纸和血糖仪测定血糖值。
结果如图3、图4所示,HFD Model组小鼠OGTT的曲线下面积明显高于NCD Control组(P < 0.001),显示经高脂饮食喂养小鼠口服葡萄糖耐量受损,同时与HFD Model组相比,HFD + BC组OGTT曲线下面积显著降低(P < 0.05),表明解纤维素拟杆菌能够改善HFD诱导的糖耐量异常。
此外,实验第8周时进行胰岛素耐量试验(ITT),各组小鼠禁食不禁水6小时,称重、取尾尖血测量空腹血糖值(胰岛素注射前),腹腔注射胰岛素(0.75 U/kg)。然后于30、60、90和120 min(胰岛素注射后),取小鼠尾尖血经血糖试纸和血糖仪测定血糖值。
结果如图5、图6所示,与NCD Control组相比,HFD Model组小鼠ITT的曲线下面积显著增加(P < 0.001),显示经高脂饮食喂养小鼠出现胰岛素抵抗现象,同时HFD + BC组OGTT曲线下面积显著低于HFD Model组(P < 0.05),表明解纤维素拟杆菌能够改善高脂饮食引起的小鼠胰岛素抵抗。
实验8周后,各组小鼠禁食不禁水12小时,眼眶静脉丛取血,收集的血液在室温下静置30-60 min,4ºC、4000 rpm离心10 min,收集上清并分装至聚丙烯EP管,−80ºC保存,用于后续观察指标的检测。分别采用ELISA技术和葡萄糖试剂盒对小鼠血清胰岛素和葡萄糖浓度进行检测,结果如图7、图8所示,HFD + BC组血清胰岛素和葡萄糖浓度显著低于HFDModel组(P < 0.001),表明解纤维素拟杆菌能够改善高脂饮食引起的小鼠血糖异常与胰岛素抵抗。
实施例 4:解纤维素拟杆菌能够改善高脂饮食引起的小鼠体内炎症
根据ELISA试剂盒步骤检测小鼠血清炎症标志物CRP(C-反应蛋白)、促炎因子白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α),抗炎因子白介素10(IL-10)的浓度,以此考察解纤维素拟杆菌对高脂饮食引起的小鼠炎症的影响。结果如表2所示,与NCDControl组相比,HFD Model组小鼠CRP、IL-1β、IL-6和TNF-α水平显著升高(P < 0.05),IL-10含量显著降低,表明经高脂喂养引起小鼠体内炎症;同时HFD + BC组小鼠CRP、IL-1β、IL-6和TNF-α水平显著低于HFD Model组(P < 0.05),IL-10含量显著增高,表明解纤维素拟杆菌能够降低促炎因子、增加抗炎因子水平,改善高脂饮食引起的小鼠体内炎症。
表2 干预4周后小鼠血清中相关炎症指标浓度
实施例5:解纤维素拟杆菌能够增强高脂饮食喂养小鼠的免疫
利用ELISA技术对小鼠血液内免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)含量进行检测,以此考察解纤维素拟杆菌对高脂小鼠免疫的影响。结果如表3所示,与NCD Control组相比,HFD Model组小鼠IgA、IgM与IgG水平显著降低(P < 0.05),表明小鼠进食高脂饲料后机体免疫力下降,;同时HFD + BC组小鼠IgA、IgM与IgG水平显著低于HFDModel组(P < 0.05),表明解纤维素拟杆菌能够增强高脂小鼠的免疫。
表3 干预4周后小鼠血清中免疫球蛋白A、免疫球蛋白M、免疫球蛋白G含量
实施例6:解纤维素拟杆菌干预未见小鼠出现不良反应
采用生化检测试剂盒及病理组织切片对解纤维素拟杆菌干预后的小鼠是否存在肝肾损伤进行评估。结果如表4所示,肝功能代表性指标丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)及肾功能代表性指标肌酐(SCr)、尿素氮(BUN)在解纤维素拟杆菌给药组小鼠未见异常;同时对肝肾组织进行了HE染色,如图9所示,病理结果未见解纤维素拟杆菌干预后引起组织病理损伤,初步表明解纤维素拟杆菌安全性良好。
表4 干预4周后小鼠肝肾功能相关指标浓度
表2-4中,结果是以平均值 ± SD值表示,*P < 0.05、**P < 0.01、***P < 0.001表示HFD Model与NCD Control组相比差异具有统计学意义,#P < 0.05、##P < 0.01、###P< 0.001表示HFD + BC与HFD Model组相比差异具有统计学意义。
本发明中的具体实施例仅是对本发明的解释,其并不对本发明限制,本领域技术人员在阅读完本说明书后可以根据需要对本实施例做出没有创造性贡献的修改,但只要在本发明的权利要求范围内都受到专利法的保护。
Claims (10)
1.一种解纤维素拟杆菌在制备药物中的应用,其特征在于,所述药物用于预防或治疗胰岛素抵抗或2型糖尿病,所述解纤维素拟杆菌是解纤维素拟杆菌(Bacteroides cellulosilyticus),其保藏编号为DSM14838。
2.根据权利要求1所述应用,其特征在于,所述药物中解纤维素拟杆菌是唯一活性成分。
3.根据权利要求1所述应用,其特征在于,所述药物是组合物,所述解纤维素拟杆菌是其中的一种活性成分。
4.根据权利要求1所述应用,其特征在于,所述药物含有1×105-1×1014CFU/mL或1×105-1×1014CFU/g的解纤维素拟杆菌。
5.根据权利要求1所述应用,其特征在于,所述药物还包括药学载体,所述药学载体是乳糖、葡萄糖、蔗糖、山梨糖醇、甘露糖、海藻糖、淀粉、阿拉伯胶、磷酸钙、藻酸盐、明胶、硅酸钙、细结晶纤维素、聚乙烯吡咯烷酮、纤维素、水、糖浆、甲基纤维素、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁及矿物油中的至少一种。
6.根据权利要求1所述应用,其特征在于,所述2型糖尿病是由所述胰岛素抵抗引起的。
7.根据权利要求1所述应用,其特征在于,所述应用还包括改善体重增加、糖耐量异常、免疫力降低、炎症症状的一种或两种以上。
8.根据权利要求1所述应用,其特征在于,所述药物的剂型是液体制剂或固体制剂。
9.根据权利要求1所述应用,其特征在于,所述药物的剂型为口服药。
10.根据权利要求1所述应用,其特征在于,所述药物采用胃肠道给药方式。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150216913A1 (en) * | 2012-05-25 | 2015-08-06 | Consejo Superior De Investigaciones Científicas | Bacteroides CECT 7771 and the Use Thereof in the Prevention and Treatment of Excess Weight, Obesity and Metabolic and Immunological Alterations |
WO2016172658A2 (en) * | 2015-04-23 | 2016-10-27 | Kaleido Biosciences, Inc. | Microbiome regulators and related uses thereof |
US20170333492A1 (en) * | 2014-12-08 | 2017-11-23 | The Asan Foundation | Pharmaceutical composition for preventing or treating metabolic diseases, comprising bacteroides acidifaciens as active ingredient |
CN109419816A (zh) * | 2017-08-29 | 2019-03-05 | 深圳华大生命科学研究院 | 解纤维素拟杆菌在预防和/或治疗心脏疾病方面的应用 |
CN113521109A (zh) * | 2021-06-28 | 2021-10-22 | 广州知易生物科技有限公司 | 解纤维素拟杆菌在预防和/或治疗炎症性肠病中的应用 |
CN115227724A (zh) * | 2022-09-21 | 2022-10-25 | 首都医科大学附属北京友谊医院 | 缓慢葡萄球菌在制备组合物中的应用 |
CN116531410A (zh) * | 2023-07-06 | 2023-08-04 | 首都医科大学附属北京友谊医院 | 白色葡萄球菌在制备组合物中的应用 |
-
2023
- 2023-10-08 CN CN202311289355.2A patent/CN117045686B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150216913A1 (en) * | 2012-05-25 | 2015-08-06 | Consejo Superior De Investigaciones Científicas | Bacteroides CECT 7771 and the Use Thereof in the Prevention and Treatment of Excess Weight, Obesity and Metabolic and Immunological Alterations |
US20170333492A1 (en) * | 2014-12-08 | 2017-11-23 | The Asan Foundation | Pharmaceutical composition for preventing or treating metabolic diseases, comprising bacteroides acidifaciens as active ingredient |
WO2016172658A2 (en) * | 2015-04-23 | 2016-10-27 | Kaleido Biosciences, Inc. | Microbiome regulators and related uses thereof |
CN109419816A (zh) * | 2017-08-29 | 2019-03-05 | 深圳华大生命科学研究院 | 解纤维素拟杆菌在预防和/或治疗心脏疾病方面的应用 |
CN113521109A (zh) * | 2021-06-28 | 2021-10-22 | 广州知易生物科技有限公司 | 解纤维素拟杆菌在预防和/或治疗炎症性肠病中的应用 |
CN115227724A (zh) * | 2022-09-21 | 2022-10-25 | 首都医科大学附属北京友谊医院 | 缓慢葡萄球菌在制备组合物中的应用 |
CN116531410A (zh) * | 2023-07-06 | 2023-08-04 | 首都医科大学附属北京友谊医院 | 白色葡萄球菌在制备组合物中的应用 |
Non-Patent Citations (5)
Title |
---|
C.PRESTON NEFF等: "Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties", CELL HOST MICROBE., vol. 20, no. 4, pages 535 - 547, XP055964799, DOI: 10.1016/j.chom.2016.09.002 * |
CÉLINE ROBERT等: "Bacteroides cellulosilyticus sp. nov., a cellulolytic bacterium from the human gut microbial community Free", INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, vol. 57, no. 7, pages 1516 - 1520, XP055730157, DOI: 10.1099/ijs.0.64998-0 * |
GE SONG等: "The metabolic effect of fructose on normal rats in a mild dose with glucose and saccharose as control", FOOD NUTR RES., no. 65, pages 5589 * |
汪叶青: "桑叶多糖SY01-23对人肠道菌群的活性筛选及其主要糖残基半乳糖醛酸对胰岛β细胞的毒性探究", 硕士, no. 2020, pages 057 - 181 * |
简磊等: "2型糖尿病小鼠模型构建的研究进展", 生命科学研究, vol. 23, no. 3, pages 239 * |
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