三物黄芩汤对炎症性肠病大鼠肠道菌群多样性影响初探
摘要
大鼠肠道菌群结构的影响。方法 将 20 只 SD 大鼠随机分为 4 组，分别为空白对照组、IBD 模型组、三物黄芩汤低倍组、三
物黄芩汤高倍组。每组 5 只，适应性喂养 7 天之后空白对照组继续饮用纯净水，其余 3 组连续 7 天自由饮用 3% DSS 水溶
液诱导 IBD 模型。之后三物黄芩汤低倍、高倍组停止饮用 3% DSS 水溶液，改为饮用纯净水，并以灌胃的方式分别连续给
0.5 倍浓度和 2 倍浓度中药汤剂 7 天，而 IBD 模型组仅改为饮用纯净水，不做其余处理。期间定时称量大鼠的体重，监测
并记录大鼠的精神状态、进食情况、饮水量和粪便情况等进行 DAI 评分。实验第 21 天时收集各组大鼠新鲜粪便，按步骤
进行 16S rDNA 测序分析。结果 与空白对照组相比，IBD 模型大鼠的体重增长速度和 DAI 指数出现了不同程度的下降，结
肠 HE 病理中大鼠结肠可见炎症细胞浸润、黏膜层破损、杯状细胞数量减少等情况。在使用 0.5 倍浓度的三物黄芩汤干预
后，其在体重和症状上的恢复速度和 IBD 模型组相近，未见明显差异。然而在 2 倍浓度的三物黄芩汤干预过后，大鼠体重
增长速度和 DAI 指数出现了一定程度的恢复，结肠 HE 病理中结肠组织病变也出现了不同程度的减轻。这表明三物黄芩汤
对 IBD 有较好的缓解甚至治疗作用，且呈现一定程度的剂量依赖性。16S rDNA 测序分析结果提示，大鼠肠道菌群在经过
三物黄芩汤干预后肠道菌群整体丰度未见明显差异，但是肠道菌群物种组成结构具有较大差异。其中 Lachnoclostridium 属
在 IBD 模型组中丰度明显升高，而布劳特氏菌属在三物黄芩汤治疗组丰度明显升高，该两者是区分组间差异的关键菌属，
并很可能是三物黄芩汤发挥治疗 IBD 作用的核心菌群。结论 三物黄芩汤能够较好地缓解 IBD 模型大鼠的病情进展，其作
用机制可能与其重塑 IBD 模型大鼠肠道菌群构成，直接或间接缓解肠道炎症相关。
关键词
全文:
PDF参考
[1]Gilliland A, Chan JJ, De Wolfe TJ, Yang H, Vallance BA.
Pathobionts in Inflammatory Bowel Disease: Origins, Underlying
Mechanisms, and Implications for Clinical Care. Gastroenterology.
2024;166(1):44-58.
[2]Banerjee R, Pal P, Mak JWY, Ng SC. Challenges in the
diagnosis and management of inflammatory bowel disease in
resource-limited settings in Asia. Lancet Gastroenterol Hepatol.
2020;5(12):1076-1088.
[3]Sebastian S, Siegmund B, Teferra F, et al. Promoting
equity in inflammatory bowel disease: a global approach to care.
Lancet Gastroenterol Hepatol. 2024;9(3):192-194.
[4]Bernstein CN, Eliakim A, Fedail S, et al. World
Gastroenterology Organisation Global Guidelines Inflammatory
Bowel Disease: Update August 2015. J Clin Gastroenterol.
2016;50(10):803-818.
[5] 吴 开 春 , 梁 洁 , 冉 志 华 , 等 . 炎 症 性 肠 病 诊 断 与
治 疗 的 共 识 意 见 (2018 年· 北 京 )[J]. 中 国 实 用 内 科 杂
志 ,2018,38(09):796-813.
[6]M’Koma AE. Inflammatory Bowel Disease: Clinical
Diagnosis and Surgical Treatment-Overview. Medicina (Kaunas).
2022;58(5):567.
[7]Yeshi K, Ruscher R, Hunter L, Daly NL, Loukas A,
Wangchuk P. Revisiting Inflammatory Bowel Disease: Pathology,
Treatments, Challenges and Emerging Therapeutics Including
Drug Leads from Natural Products. J Clin Med. 2020;9(5):1273.
[8]Ho GT, Cartwright JA, Thompson EJ, Bain CC, Rossi AG.
Resolution of Inflammation and Gut Repair in IBD: Translational
Steps Towards Complete Mucosal Healing. Inflamm Bowel Dis.
2020;26(8):1131-1143.
[9]Shouval DS, Rufo PA. The Role of Environmental Factors
in the Pathogenesis of Inflammatory Bowel Diseases: A Review.
JAMA Pediatr. 2017;171(10):999-1005.
[10]Morar PS, Hodgkinson JD, Thalayasingam S, et al.
Determining Predictors for Intra-abdominal Septic Complications
Following Ileocolonic Resection for Crohn’s Disease-
Considerations in Pre-operative and Peri-operative Optimisation
Techniques to Improve Outcome. J Crohns Colitis. 2015;9(6):483-
491.
[11]Kostic AD, Xavier RJ, Gevers D. The microbiome in
inflammatory bowel disease: current status and the future ahead.
Gastroenterology. 2014;146(6):1489-1499.
[12]Perna A, Hay E, Contieri M, De Luca A, Guerra G,
Lucariello A. Adherent-invasive Escherichia coli (AIEC): Cause
or consequence of inflammation, dysbiosis, and rupture of cellular
joints in patients with IBD?. J Cell Physiol. 2020;235(6):5041-
5049.
[13]Caenepeel C, Sadat Seyed Tabib N, Vieira-Silva S,
Vermeire S. Review article: how the intestinal microbiota may
reflect disease activity and influence therapeutic outcome
in inflammatory bowel disease. Aliment Pharmacol Ther.
2020;52(9):1453-1468.
[14]Shah SC, Itzkowitz SH. Colorectal Cancer in Inflammatory
Bowel Disease: Mechanisms and Management. Gastroenterology.
2022;162(3):715-730.
[15] 徐 慧 超 , 武 荣 林 , 蒋 子 文 , 等 . 基 于 中 医 气 学
理论探讨自噬在炎症性肠病中的作用 [J]. 中华中医药杂
志 ,2024,39(07):3363-3367.
[16] 荀兰兰 , 沈洪 . 古方加减治疗溃疡性结肠炎研究概
况 [J]. 山东中医药大学学报 ,2012,36(02):164-166.
[17] 张兆洲 , 王炎 , 李琦 . 三物黄芩汤研究概述及其应
用展望 [J]. 辽宁中医杂志 ,2019,46(07):1551-1554.
[18]Zhu L, Xu LZ, Zhao S, Shen ZF, Shen H, Zhan LB.
Protective effect of baicalin on the regulation of Treg/Th17
balance, gut microbiota and short-chain fatty acids in rats with
ulcerative colitis. Appl Microbiol Biotechnol. 2020;104(12):5449-
5460.
[19] 杨光勇 , 喻良锦 , 涂小华 , 等 . 黄连对溃疡性结肠炎
小鼠肠道内嗜黏蛋白益生菌 A.muciniphila 菌及肠粘膜屏障
的影响 [J]. 中国民族民间医药 ,2022,31(05):27-32.
[20]Mukherjee PK, Chandra J, Retuerto M, et al. Oral
mycobiome analysis of HIV-infected patients: identification
of Pichia as an antagonist of opportunistic fungi. PLoS Pathog.
2014;10(3):e1003996.
[21] Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson
AJ, Holmes SP. DADA2: High-resolution sample inference from
Illumina amplicon data. Nat Methods. 2016;13(7):581-583.
[22]Bolyen, Evan et al. Reproducible, interactive, scalable
and extensible microbiome data science using QIIME 2. Nature
biotechnology vol. 37,8 (2019): 852-857.
[23]Chao A, Bunge J. Estimating the number of species in a
stochastic abundance model. Biometrics. 2002;58(3):531-539.
[24]Hill TC, Walsh KA, Harris JA, Moffett BF. Using
ecological diversity measures with bacterial communities. FEMS
Microbiol Ecol. 2003;43(1):1-11.
[25]Grossberg LB, Papamichael K, Cheifetz AS. Review
article: emerging drug therapies in inflammatory bowel disease.
Aliment Pharmacol Ther. 2022;55(7):789-804.
[26] 苏晓兰 , 国嵩 , 张涛 , 等 . 炎症性肠病诊治现状及中
医药治疗特色与优势 [J]. 北京中医药 ,2020,39(03):211-215.
[27]Yan Y, Li L, Wu K, et al. A Combination of Baicalin and
Berberine Hydrochloride Ameliorates Dextran Sulfate Sodium-
Induced Colitis by Modulating Colon Gut Microbiota. J Med Food.
2022;25(8):853-862.
[28] 刘利 , 叶映泉 , 桂仲旋 , 等 . 亮菌多糖对 AOM/DSS
炎症相关性结肠癌小鼠模型及其肠道菌群的影响 [J]. 现代肿
瘤医学 ,2024,32(12):2161-2170.
[29] 朱琳 , 王敦方 , 冯雪 , 等 . 黄芩汤对炎症相关性结直
肠癌小鼠炎症及短链脂肪酸相关肠道菌群的影响 [J]. 中国实
验方剂学杂志 ,1-15.
[30]Zhang W, Zou G, Li B, et al. Fecal Microbiota
Transplantation (FMT) Alleviates Experimental Colitis in
Mice by Gut Microbiota Regulation. J Microbiol Biotechnol.
2020;30(8):1132-1141.
[31] Dandachi I, Anani H, Hadjadj L, et al. Genome analysis
of Lachnoclostridium phocaeense isolated from a patient after
kidney transplantation in Marseille. New Microbes New Infect.
2021;41:100863.
[32]Liang JQ, Li T, Nakatsu G, et al. A novel faecal
Lachnoclostridium marker for the non-invasive diagnosis of
colorectal adenoma and cancer. Gut. 2020;69(7):1248-1257.
[33]Chen W, Liu F, Ling Z, Tong X, Xiang C. Human
intestinal lumen and mucosa-associated microbiota in patients
with colorectal cancer. PLoS One. 2012;7(6):e39743.
[34]Liu X, Mao B, Gu J, et al. Blautia-a new functional genus
with potential probiotic properties?. Gut Microbes. 2021;13(1):1-
21.
[35]Rashidi A, Peled JU, Ebadi M, et al. Protective Effect
of Intestinal Blautia Against Neutropenic Fever in Allogeneic
Transplant Recipients. Clin Infect Dis. 2022;75(11):1912-1920.
[36]de Mooij CEM, van Groningen LFJ, Molendijk EBD,
Wardill HR, van der Velden WJFM, Blijlevens NMA. Blautia
Abundance and Mucosal Barrier Injury: A Complex Play of Cause
and Effect. Clin Infect Dis. 2023;76(6):1152-1153.
[37]Holmberg SM, Feeney RH, Prasoodanan P K V, et al.
The gut commensal Blautia maintains colonic mucus function
under low-fiber consumption through secretion of short-chain
fatty acids. Nat Commun. 2024;15(1):3502.
[38]Wang J, Zhang C, Guo C, Li X. Chitosan Ameliorates
DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal
Barrier Function and Improving Microflora. Int J Mol Sci.
2019;20(22):5751.
[39]Jenq RR, Taur Y, Devlin SM, et al. Intestinal Blautia Is
Associated with Reduced Death from Graft-versus-Host Disease.
Biol Blood Marrow Transplant. 2015;21(8):1373-1383.
(5 摘要 Views, 12 PDF Downloads)
Refbacks
- 当前没有refback。