CN116590200A - 约氏乳杆菌及其在制备预防和/或改善急性胰腺炎的产品中的应用 - Google Patents
约氏乳杆菌及其在制备预防和/或改善急性胰腺炎的产品中的应用 Download PDFInfo
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Abstract
本发明公开了约氏乳杆菌及其在制备预防和/或改善急性胰腺炎的产品中的应用,涉及益生菌领域。所述约氏乳杆菌的微生物保藏编号为CGMCCNo.27500。本发明通过由雨蛙肽或L‑精氨酸诱导的两种急性胰腺炎小鼠模型实验,验证了约氏乳杆菌CGMCC No.27500对急性胰腺炎的缓解和改善作用,该菌株能有效缓解急性胰腺炎小鼠胰腺组织损伤程度(水肿,炎症渗出和腺泡细胞损伤)、血清中淀粉酶和脂肪酶浓度,还能够减轻由急性胰腺炎引起的肺泡壁水肿及炎症细胞浸润程度。所述约氏乳杆菌CGMCC No.27500可用于制备预防和改善急性胰腺炎以及由急性胰腺炎引起的肺损伤的产品,具有广泛的应用前景。
Description
技术领域
本发明属于微生物领域,具体涉及一种约氏乳杆菌及其在制备预防和/或改善急性胰腺炎的产品中的应用。
背景技术
急性胰腺炎(Acute Pancreatitis,AP)是由胆道结构性梗阻、高甘油三酯血症及酗酒等多种病因导致胰酶在胰腺内被激活后引起胰腺组织自身消化、水肿、出血甚至坏死的炎症反应。临床以急性上腹痛、恶心、呕吐、发热和血胰酶增高等为特点,目前发病率约为30例/10万左右,其中15%~20%为重症急性胰腺炎(Severe Acute Pancreatitis,SAP),死亡率高达30%以上。然而,目前临床上能有效改善和治疗AP的药物不多。
肠道免疫系统的建立在AP病程中发挥着重要的作用,而肠道菌群是构成肠粘膜免疫系统的生物学屏障,在一定程度上决定了AP的严重程度。约氏乳杆菌(Lactobacillusjohnsonii)分类于乳杆菌属。研究表明,约氏乳杆菌具有良好的益生作用,如能够促进仔猪的生长并降低仔猪腹泻;防治家禽坏死性肠炎、改善肉鸡的生长性能,减少鸡体内病原菌的定植;还可以预防老龄小鼠因蛋白质能量失衡导致的免疫机能障碍,提高小鼠小肠上皮细胞抗原受体的基因表达以及预防肥胖小鼠非酒精性脂肪性肝病。然而,未见有任何现有技术报道约氏乳杆菌在急性胰腺炎中的相关预防及治疗作用。
发明内容
本发明的目的是提供一种约氏乳杆菌的新用途——用于制备预防和/或改善急性胰腺炎的产品,以克服现有改善和缓解急性胰腺炎的药物不足的问题。所述约氏乳杆菌的保藏号为CGMCC No.27500,该菌株对雨蛙肽或L-精氨酸诱导的急性胰腺炎小鼠发挥保护作用,缓解胰腺组织损伤程度,以及肺泡壁水肿及炎症细胞浸润,可作为有效成分应用到防治急性胰腺炎以及由急性胰腺炎引起的肺损伤的药物、保健食品等产品的制备中。
本发明首先提供了一种约氏乳杆菌,所述约氏乳杆菌由本课题组提取分离自无特定病原菌(Specific pathogen free,SPF)级雄性C57/BL6小鼠粪便。所述约氏乳杆菌(英文名:Lactobacillus johnsonii)菌株于2023年5月30日保藏于北京市朝阳区的中国微生物菌种保藏管理委员会普通微生物中心(简称CGMCC),微生物保藏编号为CGMCC No.27500。
本发明另一方面还提供了前面所述的约氏乳杆菌在制备预防和/或改善急性胰腺炎的产品中的应用。
优选地,所述预防和/或改善急性胰腺炎包括如下至少一项:
(1)缓解胰腺水肿、腺泡细胞损伤及炎症细胞浸润;
(2)降低血清中淀粉酶和脂肪酶浓度;
(3)减轻肺泡壁水肿及炎症细胞浸润;
(4)抑制促炎因子IL-1β、IL-6和TNF-α的表达水平。
本发明另一方面还提供了所述的约氏乳杆菌在制备预防和/或改善肺损伤的产品中的应用,所述肺损伤由急性胰腺炎引起。
优选地,所述产品包括药物、保健食品、肠内营养制剂、膳食补充剂。
本发明另一方面还提供了一种预防和/或改善急性胰腺炎的药物,所述药物包括前面所述的约氏乳杆菌。
优选地,所述药物还包括药学上可接受的药用载体和/或药用辅料。
优选地,所述药用辅料包含赋形剂和/或附加剂。
优选地,所述药物的剂型包括颗粒剂、胶囊剂、片剂、丸剂或口服液。
本发明另一方面还提供了一种预防和/或改善肺损伤的药物,所述药物包括前面所述的约氏乳杆菌,所述肺损伤由急性胰腺炎引起。
相对于现有技术,本发明的有益效果至少包括:
本发明通过由雨蛙肽或L-精氨酸诱导的两种急性胰腺炎小鼠模型实验,验证了约氏乳杆菌CGMCC No.27500对急性胰腺炎的缓解和改善作用,该菌株能有效缓解急性胰腺炎小鼠胰腺组织损伤程度(水肿,炎症渗出和腺泡细胞损伤)、血清中淀粉酶和脂肪酶浓度,还能够减轻由急性胰腺炎引起的肺泡壁水肿及炎症细胞浸润程度。所述约氏乳杆菌CGMCCNo.27500可用于制备预防和/或改善急性胰腺炎以及由急性胰腺炎引起的肺损伤的药物等产品,具有广泛的应用前景。
附图说明
图1表示本发明约氏乳杆菌对雨蛙肽诱导的急性胰腺炎小鼠急性期胰腺炎症的保护作用;其中:
A为各组小鼠胰腺组织HE染色代表图;
B为各组小鼠胰腺组织损伤程度评分;
C为各组小鼠胰腺组织CD45免疫组化代表图;
D为各组小鼠胰腺组织CD45免疫组化评分;
E为各组小鼠血清淀粉酶含量对比;
F为各组小鼠血清脂肪酶含量对比。
图2表示本发明约氏乳杆菌对雨蛙肽诱导的急性胰腺炎小鼠急性期肺损伤和全身炎症反应的保护作用;其中:
A为各组小鼠肺组织HE染色代表图;
B为各组小鼠肺组织CD45免疫组化代表图;
C为各组小鼠肺组织CD45免疫组化评分;
D为各组小鼠血清中IL-6含量对比;
E为各组小鼠血清中TNF-α含量对比;
F为各组小鼠血清中IL-1β含量对比。
图3表示本发明约氏乳杆菌对L-精氨酸诱导的急性胰腺炎小鼠的保护作用;其中:
A为各组小鼠胰腺组织HE染色代表图;
B为各组小鼠胰腺组织损伤程度评分;
C为各组小鼠血清淀粉酶含量对比;
D为各组小鼠血清脂肪酶含量对比;
E为各组小鼠肺组织HE染色代表图。
其中,数据展示为平均值±标准误差。*P<0.05,**P<0.01,***P<0.001表示采用ANOVA检验方法。
具体实施方式
以下结合附图和实施例对本发明的技术方案做进一步的说明。
如前所述,急性胰腺炎是一种炎症性胰腺疾病,是全世界最常见的消化系统疾病之一,目前临床上缺乏有效的改善和治疗药物。为解决该问题,寻找一种有效预防和/或改善急性胰腺炎的药物,本发明课题组经过大量的筛选菌株,并通过雨蛙肽诱导的急性胰腺炎小鼠模型实验,评价菌株对急性胰腺炎的防治作用,最终筛选到一株对急性胰腺炎有防治作用的菌株,所述菌株为约氏乳杆菌,其微生物保藏编号为CGMCC No.27500,并进一步提供了所述约氏乳杆菌在制备预防和/或改善急性胰腺炎的产品中的应用。优选地,所述预防和/或改善急性胰腺炎包括如下至少一项:
(1)缓解胰腺水肿、腺泡细胞损伤及炎症细胞浸润;
(2)降低血清中淀粉酶和脂肪酶浓度;
(3)减轻肺泡壁水肿及炎症细胞浸润;
(4)抑制促炎因子IL-1β、IL-6和TNF-α的表达水平。
本发明另一个目的是提供所述的约氏乳杆菌在制备预防和/或改善肺损伤的产品中的应用,所述肺损伤由急性胰腺炎引起。
一些实施例中,所述产品包括药物、保健食品、肠内营养制剂、膳食补充剂。
一些实施例中,所述保健食品还包括食品添加剂,所述食品添加剂选自:酸度调节剂、抗结剂、消泡剂、抗氧化剂、漂白剂、膨松剂、着色剂、护色剂、酶制剂、增味剂、营养强化剂、防腐剂、甜味剂、增稠剂、香料。
本发明另一个目的是提供一种预防和/或改善急性胰腺炎的药物,所述药物包括前面所述的约氏乳杆菌。
本发明另一个目的是提供一种预防和/或改善肺损伤的药物,所述药物包括前面所述的约氏乳杆菌,所述肺损伤由急性胰腺炎引起。
一些实施例中,所述药物还包括药学上可接受的药用载体和/或药用辅料。所述药物载体包含微囊、微球、纳米粒、脂质体;所述药用辅料包含赋形剂和/或附加剂,所述药用辅料包含溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、黏合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗黏合剂、整合剂、渗透促进剂、pH值调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂、赋形剂、附加剂、释放阻滞剂中的一种或几种。
一些实施例中,所述药用辅料包含赋形剂和/或附加剂。
一些实施例中,所述药物的剂型包括颗粒剂、胶囊剂、片剂、丸剂或口服液。
本发明通过由雨蛙肽或L-精氨酸诱导的两种急性胰腺炎小鼠模型实验,验证了约氏乳杆菌CGMCC No.27500对急性胰腺炎以及由急性胰腺炎引起的肺损伤的缓解和改善作用。下面将结合附图和具体实验过程详细讲述。
下述实施例中所使用的实验方法或实验条件,如无特殊说明,均按常规方法或厂家说明书进行,下述实验例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
本发明使用的实验动物为SPF级6到8周龄C57BL/6小鼠。由上海交通大学医学院附属第一人民医院实验动物中心向上海公共卫生临床中心订购并统一饲养于实验动物中心SPF级区域。本动物实验已通过医院伦理审批,伦理(IACUC)号为2019AW059。
实施例1约氏乳杆菌对急性胰腺炎急性期胰腺炎症的保护作用
1.实验方法
雨蛙肽诱导的小鼠急性胰腺炎模型的建立:6到8周龄的C57BL/6小鼠,适应1周后,随机分为3组(每组6只小鼠),分别为正常对照组(Control组)、模型组(CAE+LPS组)和治疗组(CAE+LPS+LJ组),模型组和治疗组小鼠腹腔注射雨蛙肽CAE(100μg/kg,间隔1h,连续10针)构建急性胰腺炎模型,最后一次注射雨蛙肽的同时注射5mg/kg的脂多糖LPS,Control组小鼠注射等体积生理盐水;造模前,治疗组小鼠造模前7天每天分别灌胃200μl含有108个约氏乳杆菌(LJ)的菌悬液,模型组和Control组小鼠每天分别灌胃200μl的PBS。
第一次注射雨蛙肽后12h腹腔注射5%水合氯醛麻醉处死小鼠,并进行以下处理:
(1)采集血液,制备血清,检测血清淀粉酶、血清脂肪酶含量。
(2)采集胰腺组织,制备组织切片,并进行H&E染色分析和CD45免疫组化分析。
2.实验结果
(1)约氏乳杆菌改善急性胰腺组织损伤情况
如图1所示,Control组小鼠胰腺组织结构紧密,无明显裂纹,模型组(CAE+LPS组)小鼠胰腺组织结构疏松,有明显的水肿及腺泡细胞空泡、死亡现象,而相较于模型组,治疗组(CAE+LPS+LJ组)小鼠胰腺组织损伤有明显的改善作用,组织损伤评分显著降低(图1中的A、B);此外,相较于模型组,治疗组小鼠胰腺组织的CD45阳性炎症细胞浸润情况也有了明显改善(图1中的C、D)。
(2)约氏乳杆菌降低血清淀粉酶和血清脂肪酶含量
研究表明,急性胰腺炎患者血清中的淀粉酶和脂肪酶含量会增高,因此本发明对各实验组小鼠的血清淀粉酶和血清淀粉酶含量进行测定,以验证本发明约氏乳杆菌(LJ)对急性胰腺炎的改善作用。
如图1中E和F图所示,相较于Control组,模型组小鼠血清淀粉酶和血清淀粉酶含量明显上升,而治疗组小鼠的血清淀粉酶和血清淀粉酶较模型组小鼠则有了明显下调。
以上结果表明,本发明公开的约氏乳杆菌能够改善胰腺组织损伤情况(水肿、炎症细胞浸润和腺泡细胞坏死),且能降低急性胰腺炎发生时血清淀粉酶和血清淀粉酶的含量,对急性胰腺炎急性期胰腺炎症具有明显的保护和改善作用。
实施例2约氏乳杆菌对急性胰腺炎引起的肺损伤和全身炎症反应的保护作用
1.实验方法
动物实验分组、造模处理及给药处理同实施例1。其中,第一次注射雨蛙肽后12h腹腔注射5%水合氯醛麻醉处死小鼠,并进行以下处理:
(1)采集肺组织,制备组织切片,并进行H&E染色分析和CD45免疫组化分析。
(2)采集血液,制备血清,检测血清炎症因子IL-6、TNF-α、IL-1β的含量。
2.实验结果
(1)约氏乳杆菌减轻急性胰腺炎引起的肺损伤
如图2的A-C所示,Control组小鼠肺组织未见异常,肺泡轮廓完整清晰,且未见明显的炎症细胞浸润,模型组(CAE+LPS组)小鼠肺泡壁出现了明显水肿、增厚现象,部分肺泡扩张,同时有大量炎症细胞浸润,而相较于模型组,治疗组(CAE+LPS+LJ组)小鼠肺组织的肺泡壁水肿和炎症细胞浸润情况具有明显改善,组织损伤评分显著降低。
(2)约氏乳杆菌减轻急性胰腺炎引起的全身炎症反应
采用生物素双抗体夹心酶联免疫吸附法(ELISA)测定各实验组小鼠血清中促炎因子IL-6、TNF-α和IL-1β的含量,以验证本发明约氏乳杆菌对急性胰腺炎引起的全身炎症反应的改善作用。
如图2的D-F所示,相较于Control组,模型组小鼠血清中促炎因子IL-6、TNF-α和IL-1β的含量均明显上升,而治疗组小鼠血清中促炎因子IL-6、TNF-α和IL-1β的含量较模型组均有了明显降低。
以上结果表明,本发明公开的约氏乳杆菌能够减轻由急性胰腺炎引起的系统损伤(肺损伤和全身炎症反应)。
实施例3
本发明还构建了另一经典的急性胰腺炎模型以验证本发明公开的约氏乳杆菌LJ对急性胰腺炎的保护作用。
1.实验方法
L-精氨酸(L-Arg)诱导的小鼠急性胰腺炎模型的建立:6到8周龄的C57BL/6小鼠,适应1周后,随机分为3组(每组5只小鼠),分别为正常对照组(Control组)、模型组(L-Arg组)和治疗组(L-Arg+LJ组),模型组和治疗组小鼠腹腔注射L-精氨酸(4.5g/kg,间隔1h,连续2针)构建急性胰腺炎模型,Control组小鼠注射等体积生理盐水;造模前,治疗组小鼠造模前7天每天分别灌胃200μl含有108个约氏乳杆菌LJ的菌悬液,模型组和Control组小鼠每天分别灌胃200μl的PBS。
第二次注射L-精氨酸结束时记为0天,第3天时腹腔注射5%水合氯醛麻醉处死小鼠,并进行以下处理:
(2)采集血液,制备血清,检测血清淀粉酶、血清脂肪酶含量。
(2)采集胰腺组织和肺组织,分别制备组织切片,并进行H&E染色分析和CD45免疫组化分析。
2.实验结果
如图3所示,在L-精氨酸诱导的小鼠急性胰腺炎模型中,本发明公开的约氏乳杆菌LJ同样能够显著地减轻胰腺水肿、坏死和炎症细胞浸润情况,组织损伤评分显著降低(图3中的A、B);并且显著降低小鼠肺泡壁水肿和炎症细胞浸润(图3中的E);同时,还能够降低能降低急性胰腺炎发生时血清淀粉酶和血清淀粉酶的含量,对急性胰腺炎急性期胰腺炎症具有明显的保护和改善作用(图3中的C、D)。
综上所述,本发明通过由雨蛙肽或L-精氨酸诱导的两种急性胰腺炎小鼠模型实验,验证了约氏乳杆菌CGMCC No.27500对急性胰腺炎以及由急性胰腺炎引起的肺损伤的缓解和改善作用。所述约氏乳杆菌CGMCC No.27500可用于制备预防和/或改善急性胰腺炎以及由急性胰腺炎引起的肺损伤的药物等产品,具有广泛的应用前景。
尽管本发明的内容已经通过上述优选实施例作了详细介绍,但应当认识到上述的描述不应被认为是对本发明的限制。在本领域技术人员阅读了上述内容后,对于本发明的多种修改和替代都将是显而易见的。因此,本发明的保护范围应由所附的权利要求来限定。
Claims (10)
1.一种约氏乳杆菌,其特征在于,所述约氏乳杆菌的微生物保藏编号为CGMCCNo.27500。
2.权利要求1所述的约氏乳杆菌在制备预防和/或改善急性胰腺炎的产品中的应用。
3.如权利要求2所述的应用,其特征在于,所述预防和/或改善急性胰腺炎包括如下至少一项:
(1)缓解胰腺水肿、腺泡细胞损伤及炎症细胞浸润;
(2)降低血清中淀粉酶和脂肪酶浓度;
(3)减轻肺泡壁水肿及炎症细胞浸润;
(4)抑制促炎因子IL-1β、IL-6和TNF-α的表达水平。
4.权利要求1所述的约氏乳杆菌在制备预防和/或改善肺损伤的产品中的应用,其特征在于,所述肺损伤由急性胰腺炎引起。
5.如权利要求2-4中任一项所述的应用,其特征在于,所述产品包括药物、保健食品、肠内营养制剂、膳食补充剂。
6.一种预防和/或改善急性胰腺炎的药物,其特征在于,所述药物包括权利要求1所述的约氏乳杆菌。
7.如权利要求6所述的预防和/或改善急性胰腺炎的药物,其特征在于,所述药物还包括药学上可接受的药用载体和/或药用辅料。
8.如权利要求7所述的预防和/或改善急性胰腺炎的药物,其特征在于,所述药用辅料包含赋形剂和/或附加剂。
9.如权利要求6所述的预防和/或改善急性胰腺炎的药物,其特征在于,所述药物的剂型包括颗粒剂、胶囊剂、片剂、丸剂或口服液。
10.一种预防和/或改善肺损伤的药物,其特征在于,所述药物包括权利要求1所述的约氏乳杆菌,所述肺损伤由急性胰腺炎引起。
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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 |
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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 |
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