茯砖茶对葡聚糖硫酸钠诱导UC小鼠炎症及肠道微生物的影响

黄翔翔; 谭婷; 禹利君; 王坤波; 黄建安; 徐诗钰; 刘仲华

doi:10.13305/j.cnki.jts.2021.05.004

茶叶科学 >

2021 , Vol. 41 >Issue 5: 681 - 694

DOI: https://doi.org/10.13305/j.cnki.jts.2021.05.004

研究报告

茯砖茶对葡聚糖硫酸钠诱导UC小鼠炎症及肠道微生物的影响

黄翔翔 ,
谭婷 ,
禹利君 ,
王坤波 ,
黄建安 ,
徐诗钰 ,
刘仲华

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1.湖南农业大学茶学教育部重点实验室,湖南长沙 410128;
2.国家植物功能成分利用工程技术研究中心,湖南长沙 410128;
3.湖南省植物功能成分利用协同创新中心,湖南长沙 410128

黄翔翔,男,博士研究生,主要从事茶叶功能成分及药理研究。

收稿日期: 2021-02-23

修回日期: 2021-04-15

网络出版日期: 2021-10-12

基金资助

国家重点研发计划（2018YFC1604403）、湖南省科技厅黑茶重点研发项目（2017NK2180）、湖南省大学生创新创业训练计划（201910537089）、财政部和农业农村部：国家现代农业产业技术体系

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Effects of Fu Brick Tea on Inflammation and Intestinal Microflora Diversity in Mice with DSS-induced Ulcerative Colitis

HUANG Xiangxiang ,
TAN Ting ,
YU Lijun ,
WANG Kunbo ,
HUANG Jian'an ,
XU Shiyu ,
LIU Zhonghua

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1. Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China;
2. National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China;
3. Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha 410128, China

Received date: 2021-02-23

Revised date: 2021-04-15

Online published: 2021-10-12

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摘要

为研究茯砖茶对葡聚糖硫酸钠（Dextran sulfate sodium,DSS）诱导的溃疡性结肠炎（Ulcerative colitis,UC）小鼠的抗炎作用及肠道微生物多样性的影响,将60只C57BL/6雌性小鼠随机分成正常对照组、10 mg·kg^-1 EGCG对照组、高剂量茯砖茶（300 mg·kg^-1）对照组、DSS模型组、DSS+10 mg·kg^-1 EGCG处理组、DSS+低剂量茯砖茶（100 mg·kg^-1）处理组、DSS+中剂量茯砖茶（150 mg·kg^-1）处理组、DSS+高剂量茯砖茶（300 mg·kg^-1）处理组,对照组n=5,处理组n=9。DSS造模1周后,灌喂处理4周,试验5周后处死小鼠,观察小鼠结肠组织病理学变化,评估小鼠结肠炎疾病指数（Disease activity index,DAI）,检测小鼠血清中IL-6、IL-8、IL-1β、TNF-α、IFN-γ等炎性因子水平及小鼠结肠组织中JAK2、STAT3基因表达水平,利用PCR-DGGE、克隆测序等技术分析小鼠肠道微生物菌群多样性。结果表明,与DSS模型组相比,灌喂EGCG和不同剂量茯砖茶后,小鼠生存质量、结肠组织形态明显改善,显著降低了小鼠血清中IL-6、IL-8、IL-1β、TNF-α、IFN-γ水平（P<0.05）;显著降低JAK2、STAT3基因表达（P<0.05）,抑制了JAK2/STAT3炎性信号通路;肠道微生物多样性增加、丰富度提高,不同处理组优势菌群发生变化。综上所述,茯砖茶可通过抑制JAK2/STAT3炎性信号通路以及调节小鼠肠道微生物多样性来改善DSS诱导的小鼠溃疡性结肠炎。

关键词： 茯砖茶; 溃疡性结肠炎; 炎性指标; 肠道微生物多样性; 变性梯度凝胶电泳

本文引用格式

黄翔翔 , 谭婷 , 禹利君 , 王坤波 , 黄建安 , 徐诗钰 , 刘仲华 . 茯砖茶对葡聚糖硫酸钠诱导UC小鼠炎症及肠道微生物的影响[J]. 茶叶科学, 2021 , 41(5) : 681 -694 . DOI: 10.13305/j.cnki.jts.2021.05.004

Abstract

In this study, we investigated the effects of Fu brick tea on the anti-inflammation and intestinal microflora of ulcerative colitis (UC) mice induced by Dextran sulfate sodium (DSS). Sixty C57BL/6 female mice were randomly divided into the normal control group, 10 mg·kg-1 EGCG control group, high dose brick tea (300 mg·kg-1, HBT) control group, DSS model group, DSS＋10 mg·kg-1 EGCG group, DSS＋low dose brick tea (100 mg·kg-1, LBT) group, DSS＋middle dose brick tea (150 mg·kg-1, MBT) group and DSS＋HBT group, with the control groups n=5 and the treatment groups n=9. After 1 week of DSS modeling, the mice were gavaged for 4 weeks. The mice were executed after 5 weeks of the treatments. The histopathological changes of mice colon were observed, and the disease activity index (DAI) of mice colitis was assessed. The levels of IL-6, IL-8, IL-1β, TNF-α and IFN-γ inflammatory factors in mice serum and the expression levels of JAK2 and STAT3 genes in mice colon tissues were measured. The intestinal microflora of mice was analyzed by PCR-DGGE and clone sequencing techniques. The results show that compared with the DSS model group, the quality of survival and colonic tissue morphology of mice were significantly improved after feeding EGCG and different concentrations of brick tea, and the levels of inflammatory factors IL-6, IL-8, IL-1β, TNF-α and IFN-γ in mice serum were significantly reduced (P<0.05). Moreover, the expressions of JAK2 and STAT3 genes were significantly reduced (P<0.05) JAK2/STAT3 inflammatory signaling pathway was inhibited; and intestinal microflora diversity and richness were increased significantly. The dominant bacterial flora in different treatment groups were changed as well. In conclusion, Fu brick tea can ameliorate DSS-induced UC injury by inhibiting JAK2/STAT3 inflammatory signaling pathway and modulating intestinal microflora diversity.

Key words： Fu brick tea; ulcerative colitis; inflammation factors; intestinal microflora diversity; PCR-DGGE

参考文献

[1] Bernstein C N.Epidemiologic clues to inflammatory bowel disease[J]. Current Gastroenterology Reports, 2010, 12(6): 495-501.
[2] Rogler G.Chronic ulcerative colitis and colorectal cancer[J]. Cancer Letters, 2013, 345(2): 235-241.
[3] Polytarchou C, Hommes D W, Palumbo T, et al.MicroRNA214 is associated with progression of ulcerative colitis, and inhibition reduces development of colitis and colitis-associated cancer in mice[J]. Gastroenterology, 2015, 149(4): 981-992.
[4] Akanda M R, Nam H H, Tian W, et al.Regulation of JAK2/STAT3 and NF-κB signal transduction pathways; Veronica polita alleviates dextran sulfate sodium-induced murine colitis[J]. Biomedicine & Pharmacotherapy, 2018, 100: 296-303.
[5] Fava F, Danese S.Intestinal microbiota in inflammatory bowel disease: friend of foe?[J]. World Journal of Gastroenterology, 2011, 17(5): 557-566
[6] Liang J, Sha S M, Wu K C.Role of the intestinal microbiota and fecal transplantation in inflammatory bowel diseases[J]. Journal of Digestive Diseases, 2015, 15(12): 641-646.
[7] Berry D, Reinisch W.Intestinal microbiota: a source of novel biomarkers in inflammatory bowel diseases?[J]. Best Practice and Research Clinical Gastroenterology, 2013, 27(1): 47-58.
[8] Peloquin J M, Nguyen D D.The microbiota and inflammatory bowel disease: insights from animal models[J]. Anaerobe, 2013, 24(12): 102-106.
[9] Han D S.Current status and prospects of intestinal microbiome studies[J]. Intestinal Research, 2014, 12(3): 178-183.
[10] Schippa S, Conte M.Dysbiotic events in gut microbiota: impact on human health[J]. Nutrients, 2014, 6(12): 5786-5805.
[11] Sood A, Ahuja V, Kedia S, et al.Diet and inflammatory bowel disease: the Asian working group guidelines[J]. Indian Journal of Gastroenterology, 2019, 38(3): 220-246.
[12] De C M M, Pascoal L B, Steigleder K M, et al. Role of diet and nutrition in inflammatory bowel disease[J]. Journal of Experimental Medicine, 2021, 11(1): 1-16.
[13] Brzozowski T, Szmyd J, Surmiak M, et al.Probiotics in the mechanism of protection against gut inflammation and therapy of gastrointestinal disorders[J]. Current Pharmaceutical Design, 2014, 20(7): 1149-1155.
[14] Wang Y L, Xu A Q, Liu P, et al.Effects of Fuzhuan brick-tea water extract on mice infected with E. coli O157:H7[J]. Nutrients, 2015, 7(7): 5309-5326.
[15] Chen G, Wang M, Xie M, et al.Evaluation of chemical property, cytotoxicity and antioxidant activity in vitro and in vivo of polysaccharides from Fuzhuan brick teas[J]. International Journal of Biological Macromolecules, 2018, 116: 120-127.
[16] 刘婷, 李颂, 张赓, 等. 冠突散囊菌和茯砖茶的健康功效[J]. 食品研究与开发, 2016, 37(5): 208-212.
Liu T, Li S, Zhang G, et al.Health efficacy of Eurotium cristatum and Fuzhuan brick tea[J]. Food Research and Development, 2016, 37(5): 208-212.
[17] Yanai H, Salomon N, Lahat A.Complementary therapies in inflammatory bowel diseases[J]. Current Gastroenterology Reports, 2016, 18(12): 62. doi: 10.1007/s11894-016-0537-6.
[18] 胡安恺, 姚立筠, 赵悦伶, 等. 茯砖茶提取物对葡聚糖硫酸钠诱导小鼠炎症性肠病的保护作用研究[J]. 茶叶科学, 2019, 39(6): 641-651.
Hu A K, Yao L Y, Zhao Y L, et al.Protective effects of fu brick tea extracts on inflammatory bowel disease induced by dextran sulfate sodium in mice[J]. Journal of Tea Science, 2019, 39(6): 641-651.
[19] Oz H S, Chen T S, Mcclain C J, et al.Antioxidants as novel therapy in a murine model of colitis[J]. Journal of Nutritional Biochemistry, 2005, 16(5): 297-304.
[20] Oz H S, Chen T S, Flomenhoft D, et al.Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models[J]. Gastroenterology, 2013, 144(5): 813. doi: 10.1016/S0016-5085(13)63013-9.
[21] 周方, 欧阳建, 黄建安, 等. 茶多酚对肠道微生物的调节作用研究进展[J]. 茶叶科学, 2019, 39(6): 619-630.
Zhou F, Ouyang J, Huang J A, et al.Advances in research on the regulation of tea polyphenols and effects on intestinal flora[J]. Journal of Tea Science, 2019, 39(6): 619-630.
[22] Yang X, Yang Y, Wang Y, et al.Excretory/secretory products from trichinella spiralis adult worms ameliorate DSS-induced colitis in mice[J]. Plos One, 2014, 9(5): e96454. doi: 10.1371/journal.pone.0096454.
[23] Yu C G, Huang Q.Recent progress on the role of gut microbiota in the pathogenesis of inflammatory bowel disease[J]. Journal of Digestive Diseases, 2013, 14(10): 513-517.
[24] Gentschew L, Ferguson L R.Role of nutrition and microbiota in susceptibility to inflammatory bowel diseases[J]. Molecular Nutrition & Food Research, 2012, 56(4): 524-535.
[25] Fan F Y, Sang L X, Jiang M.Catechins and their therapeutic benefits to inflammatory bowel disease[J]. Molecules, 2017, 22(3): 484. doi: 10.3390/molecules22030484.
[26] Gong Z P, Ouyang J, Wu X L, et al.Dark tea extracts: chemical constituents and modulatory effect on gastrointestinal function[J]. Biomedicine and Pharmacotherapy, 2020, 130: 110514. doi: 10.1016/j.biopha.2020.110514.
[27] 陆英, 钟晓红, 操君喜, 等. 茯砖茶中黄酮类化合物的分离与鉴定[J]. 现代食品科技, 2017, 33(3): 285-294.
Lu Y, Zhong X H, Cao J X, et al.Isolation and identification of the flavones from Fuzhuan tea[J]. Modern Food Science and Technology, 2017, 33(3): 285-294.
[28] Zou X W, Li Y, Zhang X N, et al.A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum[J]. Molecules, 2014, 19(11): 17839-17847.
[29] Zhao H, Zhang H, Wu H, et al.Protective role of 1,25(OH)₂ vitamin D₃ in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice[J]. BMC Gastroenterol, 2012, 12: 57. doi: 10.1186/1471-230X-12-57.
[30] Murano M, Maemura K, Hirata I, et al.Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis[J]. Clinical and Experimental Immunology, 2000, 120(1): 51-58.
[31] Elinav E, Nowarski R, Thaiss C A, et al.Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms[J]. Nature Reviews Cancer, 2013, 13(11): 759-771.
[32] Danese S, Argollo M, Le B C, et al.JAK selectivity for inflammatory bowel disease treatment: does it clinically matter?[J]. Gut, 2019, 68(10): 1893-1899.
[33] Wang J, Zhu G, Sun C, et al.TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway[J]. Microbial Cell Factories, 2020, 19(1): 158. doi: 10.1186/s12934-020-01417-x.
[34] Chen H, Xia Y, Zhu S, et al.Lactobacillus plantarum LP-Onlly alters the gut flora and attenuates colitis by inducing microbiome alteration in interleukin-10 knockout mice[J]. Molecular Medicine Reports, 2017, 16(5): 5979-5985.
[35] Konarska K, Cieszkowski J, Warzecha Z, et al.Treatment with obestatin—a ghrelin gene-encoded peptide—reduces the severity of experimental colitis evoked by trinitrobenzene sulfonic acid[J]. International Journal of Molecular Sciences, 2018, 19(6): 1643. doi: 10.3390/ijms19061643.
[36] Liu J, Cai J, Fan P, et al.The abilities of salidroside on ameliorating inflammation, skewing the imbalanced nucleotide oligomerization domain-like receptor family pyrin domain containing 3/autophagy, and maintaining intestinal barrier are profitable in colitis[J]. Front Pharmacol, 2019, 10: 1385. doi: 10.3389/fphar.2019.01385.
[37] 赵春苗, 徐春厚. 变性梯度凝胶电泳技术及其在动物肠道菌群研究中的应用[J]. 中国畜牧兽医, 2012, 39(7): 62-65.
Zhao C M, Xu C H.Review on denaturing gradient gel electrophoresis and its application in animal intestinal bacterial community[J]. China Animal Husbandry and Veterinary Medicine, 2012, 39(7): 62-65.
[38] Gu S H, Chen D D, Zhang J N, et al.Bacterial community mapping of the mouse gastrointestinal tract[J]. Plos One, 2013, 8(10): e74957. doi: 10.1371/journal.pone.0074957.
[39] Stiles B G, Pradhan K, Fleming J M, et al.Clostridium and bacillus binary enterotoxins: bad for the bowels, and eukaryotic being[J]. Toxins, 2014, 6(9): 2626-2656.
[40] Moschen A R, Gerner R R, Wang J, et al.Lipocalin 2 protects from inflammation and tumorigenesis associated with gut microbiota alterations[J]. Cell Host Microbe, 2016, 19(4): 455-469.
[41] Stenman L K, Burcelin R, Lahtinen S.Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans-towards treatment with probiotics[J]. Beneficial Microbes, 2016, 7(1): 11-22.
[42] Jangi S, Gandhi R, Cox L M, et al.Alterations of the human gut microbiome in multiple sclerosis[J]. Nature Communications, 2016, 7: 12015. doi: 10.1038/ncomms12015.
[43] Chen B, Ni X, Sun R, et al.Commensal bacteria-dependent CD8αβ+ T cells in the intestinal epithelium produce antimicrobial peptides[J]. Frontiers in Immunology, 2018, 9: 1065. doi: 10.3389/fimmu.2018.01065.

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