为研究果胶对牙龈卟啉单胞菌(Porphyromonas gingivalis, Pg)加剧的结肠炎的干预效果,将小鼠随机分为3组:模型组、Pg处理组、果胶治疗组。在1~7 d,各组小鼠给予2%葡聚糖硫酸钠(dextran sodium sulphate,DSS),建立DSS诱导的结肠炎小鼠模型。在1~14 d,Pg处理组和果胶治疗组小鼠灌胃1×108 CFU Pg。此外,连续14 d给予果胶组小鼠200 mg/kg果胶。检测各组小鼠的体重变化、脾脏指数、结肠长度、脾脏免疫T细胞情况、结肠病理组织、血清细胞因子水平及肠道菌群。研究结果显示,Pg能加剧小鼠结肠炎症状,包括体重减轻、结肠长度缩短、肠道组织受损严重加剧,进一步实验发现小鼠脾脏免疫Th17细胞增加、血清细胞因子水平增加,肠道菌群紊乱。果胶处理后,缓解了小鼠的结肠炎症状,减轻了体重下降、结肠缩短和肠道组织的损伤,并降低了血清中细胞因子水平,缓解了肠道菌群紊乱。
Abstract
To investigate the intervention effect of pectin on exacerbated colitis induced by Porphyromonas gingivalis (Pg), mice were randomly assigned into three groups, including model group, Pg treatment group, and pectin treatment group.From days 1 to 7, all groups of mice were administered 2% DSS to establish a DSS-induced colitis mouse model.From days 1 to 14, mice in the Pg group and pectin group were orally gavaged with 1×108 CFU Pg.Additionally, mice in the pectin group received continuous pectin treatment at a dose of 200 mg/kg for 14 days.The body weight, spleen index, colon length, splenic immune T-cell status, colonic histopathology, serum cytokine levels, and intestinal microbiota of each group of mice were examined.Results showed that Pg exacerbated colitis symptoms in mice, including body weight loss, colon shortening and exacerbated colonic tissue damage.Further experiments revealed increased splenic immune Th17 cells, elevated serum cytokine levels, and disrupted gut microbiota.Treatment with pectin alleviated colitis symptoms in mice, attenuating weight loss, colon shortening, and intestinal tissue damage, while also reducing serum cytokine levels and ameliorating disruption of gut microbiota.
关键词
果胶 /
牙龈卟啉单胞菌 /
结肠炎 /
Th17 /
肠道菌群
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Key words
pectin /
Porphyromonas gingivalis /
colitis /
Th17 /
gut microbiota
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参考文献
[1] ZHAO X D, LIU J B, ZHANG C, et al.Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase[J].International Journal of Oral Science, 2021, 13(1):31.
[2] LAMONT R J, FITZSIMONDS Z R, WANG H Z, et al.Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma[J].Periodontology 2000, 2022, 89(1):154-165.
[3] TAN Q, MA X, YANG B, et al.Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils[J].Gut Microbes, 2022, 14(1):2073785.
[4] KITAMOTO S, NAGAO-KITAMOTO H, JIAO Y Z, et al.The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis[J].Cell, 2020, 182(2):447-462.
[5] KAUR S, BANSAL Y, KUMAR R, et al.A panoramic review of IL-6:Structure, pathophysiological roles and inhibitors[J].Bioorganic & Medicinal Chemistry, 2020, 28(5):115327.
[6] CHANG D H, XING Q, SU Y, et al.The conserved non-coding sequences CNS6 and CNS9 control cytokine-induced rorc transcription during T helper 17 cell differentiation[J].Immunity, 2020, 53(3):614-626.
[7] DE VOS W M, TILG H, VAN HUL M, et al.Gut microbiome and health:Mechanistic insights[J].Gut, 2022, 71(5):1020-1032.
[8] LIU D, TANG W, HUANG X-J, et al.Structural characteristic of pectin-glucuronoxylan complex from Dolichos lablab L.hull[J].Carbohydrate Polymers, 2022, 298:120023.
[9] PEDROSA L F, RAZ A, FABI J P.The complex biological effects of pectin:Galectin-3 targeting as potential human health improvement?[J].Biomolecules, 2022, 12(2):289.
[10] FAN L L, ZUO S, TAN H Z, et al.Preventive effects of pectin with various degrees of esterification on ulcerative colitis in mice[J].Food & Function, 2020, 11(4):2886-2897.
[11] 田春雨. 乳酸杆菌对DSS诱导的小鼠溃疡性结肠炎的抑制作用[D].哈尔滨:哈尔滨工业大学, 2018.
TIAN C Y.Lactobacilli inhibit DSS-induced ulcerative colitis in mice[D].Harbin:Harbin Institute of Technology, 2018.
[12] 陈非玥, 洪龙胜, 李婉雁, 等.白术多糖对小鼠胸腺与脾脏指数、组织结构及p38/MAPK信号通路的影响[J].动物医学进展, 2021, 42(12):43-49.
CHEN F Y, HONG L S, LI W Y, et al, Effect of polysaccharide of Atractylodes macrocephala koidz on thymus and spleen indexes and tissue structure and p38/MAPK signaling pathway in mice[J] Progress in Veterinary Medicine, 2021, 42(12):43-49.
[13] 陈巍, 韩峥, 邹艳丽, 等.溃疡性结肠炎小鼠血清miR-23a-3p和miR-27a-3p的表达水平及其作用的研究[J].上海交通大学学报(医学版), 2020, 40(8):1069-1074.
CHEN W, HAN Z, ZOU Y L, et al.Expressions and effects of serum miR-23a-3p and miR-27a-3p in mice with ulcerative colitis[J] Journal of Shanghai Jiaotong University(Medical Science), 2020, 40(8):1069-1074.
[14] ERBEN U, LODDENKEMPER C, DOERFEL K, et al.A guide to histomorphological evaluation of intestinal inflammation in mouse models[J].International Journal of Clinical and Experimental Pathology, 2014, 7(8):4557-4576.
[15] 张桢, 高擎燏, 崔雷鸿, 等.植物乳杆菌+菊粉合生元缓解DSS诱导小鼠溃疡性结肠炎的研究[J].中国畜牧杂志, 2021, 57(8):224-229.
ZHANG Z, GAO Q Y, CUI L H, et al.Study on Lactobacillus Plantarum-inulin synbiotics to relieve DSS-induced ulcerative colitis in mice[J].Chinese Journal of Animal Science, 2021, 57(8):224-229.
[16] 余天. 天然抗氧化物对小麦麸质蛋白诱导C57BL/6小鼠肠道炎症的干预作用及其工业化生产设计[D].南昌:南昌大学, 2021.
YU T.Intervention effect of natural antioxidants on intestinal inflammation induced by wheat gluten proteins in C57BL/6 mice and its process design in industrial scale[D].Nanchang:Nanchang University, 2021.
[17] LI P, LI M, WU T, et al.Systematic evaluation of antimicrobial food preservatives on glucose metabolism and gut microbiota in healthy mice[J].NPJ Science of Food, 2022, 6(1):42.
[18] BRITTO S L, KRISHNA M, KELLERMAYER R.Weight loss is a sufficient and economical single outcome measure of murine dextran sulfate sodium colitis[J].FASEB BioAdvances, 2019, 1(8):493-497.
[19] ZHANG B W, ZHAO C Y, ZHANG X J, et al.An elemental diet enriched in amino acids alters the gut microbial community and prevents colonic mucus degradation in mice with colitis[J].mSystems, 2022, 7(6):e0088322.
[20] 袁余懿, 刘与进, 范恒.Th17 细胞及其相关细胞因子在 IBD 中研究新进展[J].世界华人消化杂志, 2021, 7(24):1402-1409.
YUAN Y Y, LIU Y J, FAN H.New progress in research of Th17 cells and related cytokines in inflammatory bowel disease[J].World Chinese Journal of Digestology, 2021, 7(24):1402-1409
[21] CHENG H, WANG L B, YANG B L, et al.Cutting edge:Inhibition of glycogen synthase kinase 3 activity induces the generation and enhanced suppressive function of human IL-10+ FOXP3+-induced regulatory T cells[J].Journal of Immunology, 2020, 205(6):1497-1502.
[22] BYNDLOSS M X, OLSAN E E, RIVERA-CHÁVEZ F, et al.Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion[J].Science, 2017, 357(6351):570-575.
[23] CAI X S, DENG L, MA X G, et al.Altered diversity and composition of gut microbiota in Wilson's disease[J].Scientific reports, 2020, 10(1):21825.
[24] KATO T, YAMAZAKI K, NAKAJIMA M, et al.Oral administration of porphyromonas gingivalis alters the gut microbiome and serum metabolome[J].mSphere, 2018, 3(5):e00460-e00418.
[25] CANI P D, DEPOMMIER C, DERRIEN M, et al.Akkermansia muciniphila:Paradigm for next-generation beneficial microorganisms[J].Nature Reviews Gastroenterology & Hepatology, 2022, 19(10):625-637.
[26] VINASCO K, MITCHELL H M, KAAKOUSH N O, et al.Microbial carcinogenesis:Lactic acid bacteria in gastric cancer[J].Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, 2019, 1872(2):188309.
[27] 刘又嘉, 贺璐, 郭艳芳, 等.肠道梭菌的研究进展[J].世界华人消化杂志, 2017, 25(22):2007-2014.
LIU Y J, HE L, GUO Y F, et al.Research progress of intestinal Clostridium[J].World Chinese Journal of Digestology, 2017;25(22):2007-2014
[28] MALFERTHEINER P, CAMARGO M C, EL-OMAR E, et al.Helicobacter pylori infection[J].Nature Reviews Disease Primers, 2023, 9:19.
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脚注
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基金
国家自然科学基金项目(31970088);科技部国家重点技术研究发展计划项目(2020YFA0509600)
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