痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 <sup>Δ</sup>

彭龙; 马佳乐; 尹艺璇; 步曦; 赵双梅

doi:10.6039/j.issn.1001-0408.2024.13.11

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痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 ^Δ

药学研究 | 更新时间：2024-07-10

- 痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 ^Δ
- Mechanism of Tongxie yaofang reducing colon hypermotility in IBS-D rats by regulating gut microbiota-ENS-MM crosstalk
- 中国药房 2024年35卷第13期页码：1605-1611
- 作者机构：
  
  天津中医药大学第二附属医院消化科，天津　300250
- 作者简介：
  
  主治医师。研究方向：中医药防治慢性脾胃病。 E-mail：772699670@qq.com
  主任医师。研究方向：中医药防治功能性胃肠病。 E-mail：aiwangzi312@163.com
- 基金信息：
  
  天津市教委科研计划项目(2021KJ152)
- DOI：10.6039/j.issn.1001-0408.2024.13.11
  中图分类号： R965
- 纸质出版日期：2024-07-15，
  
  收稿日期：2023-12-04，
  
  修回日期：2024-04-24，
- 稿件说明：
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彭龙,马佳乐,尹艺璇等.痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 ^Δ[J].中国药房,2024,35(13):1605-1611.

PENG Long,MA Jiale,YIN Yixuan,et al.Mechanism of Tongxie yaofang reducing colon hypermotility in IBS-D rats by regulating gut microbiota-ENS-MM crosstalk[J].ZHONGGUO YAOFANG,2024,35(13):1605-1611.
彭龙,马佳乐,尹艺璇等.痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 ^Δ[J].中国药房,2024,35(13):1605-1611. DOI： 10.6039/j.issn.1001-0408.2024.13.11.

PENG Long,MA Jiale,YIN Yixuan,et al.Mechanism of Tongxie yaofang reducing colon hypermotility in IBS-D rats by regulating gut microbiota-ENS-MM crosstalk[J].ZHONGGUO YAOFANG,2024,35(13):1605-1611. DOI： 10.6039/j.issn.1001-0408.2024.13.11.

摘要

目的

探讨痛泻要方通过调控肠道菌群-肠神经系统（ENS）-肌层巨噬细胞（MM）串扰减轻腹泻型肠易激综合征（IBS-D）大鼠结肠运动亢进的作用机制。

方法

将40只新生雄性SD大鼠随机分为对照组、模型组、中药组[痛泻要方2.68 g/（kg·d），以生药量计]、阳性对照组[双歧杆菌乳杆菌三联活菌片0.27 g/（kg·d）]，每组10只。除对照组外，其余3组大鼠均采用母子分离+慢性束缚+番泻叶致泻法复制肝郁脾虚证型IBS-D模型。造模后，各药物组大鼠灌胃相应药液，每天1次，持续2周。于造模结束时和给药后观察各组大鼠的粪便性质（稀便出现率、稀便率）、结肠运动功能（小球排出时间）、内脏敏感性[不同压力下的腹部回缩反射（AWR）评分]；于给药后检测各组大鼠血清脂多糖（LPS）浓度，结肠组织中骨形态生成蛋白2（BMP2）、集落刺激因子1（CSF1）、Toll样受体4（TLR4）蛋白的表达和分布情况，以及肠道菌群的多样性、物种组成及差异。

结果

造模结束时，除对照组外的其余3组大鼠均100%出现稀便，稀便率和各压力下的AWR评分均较对照组显著升高，小球排出时间均较对照组显著缩短（

＜0.01或

＜0.05）。中药组和阳性对照组大鼠的稀便出现率分别为20%、80%；中药组大鼠稀便率、各压力下的AWR评分、血清LPS浓度和结肠组织肌层中CSF1、TLR4蛋白的表达均较模型组显著降低；小球排出时间，结肠组织肌层中BMP2蛋白的平均光密度，Chao 1、Shannon、Faith’s PD、Simpson均较模型组显著延长或升高（

＜0.01或

＜0.05）；厚壁菌门/拟杆菌门相对丰度比值由低到高依次为中药组、对照组、阳性对照组、模型组，中药组大鼠的肠道菌群物种组成更贴近于对照组，其优势菌属包括普雷沃氏菌属、布劳特氏菌属等。

结论

痛泻要方能通过调节肠道菌群来调控肠道菌群-ENS-MM串扰关键蛋白BMP2、CSF1的表达，从而发挥减轻IBS-D大鼠结肠运动亢进的作用。

Abstract

OBJECTIVE

To study the effects of Tongxie yaofang reducing colon hypermotility in irritable bowel syndrome with diarrhea （IBS-D） rats by regulating gut microbiota-enteric nervous system （ENS）-muscularis macrophages （MM） crosstalk.

METHODS

Forty newborn male SD rats were randomly divided into control group， model group， TCM group [Tongxie yaofang 2.68 g/（kg·d）， calculated by raw material]， and positive control group [Live combined bifidobacterium and lactobacillus tablets 0.27 g/（kg·d）]， with 10 rats in each group. Except for the control group， the IBS-D model of liver stagnation and spleen deficiency syndrome was induced in the other 3 groups with the method of mother-child separation+chronic restraint+Folium Sennae-induced diarrhea. After modeling， the administration groups were given relevant drug liquid intragastrically， once a day， for consecutive 2 weeks. At the end of modeling and after administration， the fecal properties （the incidence and the rate of loose stools）， colonic motility （colon emptying time）， and visceral sensitivity [abdominal withdrawal reflex （AWR） scores under different pressures] of rats were observed in each group. The concentration of lipopolysaccharide （LPS） in serum was detected after medication， and the expressions and distribution of bone morphogenetic protein 2 （BMP2）， colony stimulating factor 1 （CSF1） and Toll-like receptor 4 （TLR4） in colon tissue were detected； the diversity， species composition and differences of gut microbiota were also determined.

RESULTS

At the end of modeling， compared with the control group， all rats of the other three groups suffered from loose stools （100%）， the rate of loose stools and AWR scores at different pressures increased significantly， and colon emptying time was shortened significantly （

＜0.01 or

＜0.05）. The incidences of loose stools were 20% in TCM group and 80% in the positive contr

ol group； the rate of loose stools and AWR scores at different pressures， serum concentration of LPS and protein expressions of CSF1 and TLR4 in muscle layer of colon tissue in TCM group significantly decreased， compared with the model group； colon emptying time， the average optical density of BMP2 protein in muscle layer of colon tissue， and the indexes of Chao 1， Shannon and Faith’s PD and Simpson index of rats in TCM group were all prolonged or increased significantly， compared with the model group （

＜0.01 or

＜0.05）. The relative abundance ratio of Firmicutes/Bacteroidetes， from low to high， was in the order of TCM group， control group， positive control group and model group； the species composition of gut microbiota in TCM group was closer to control group， with dominant bacterial genera including

Prevotella

and

Blautia

CONCLUSIONS

Tongxie yaofang can regulate the expressions of BMP2 and CSF1， the key proteins of gut microbiota-ENS-MM crosstalk， by changing the gut microbiota， thus alleviating the abnormal hyperfunction of colon motility in IBS-D rats.

关键词

痛泻要方腹泻型肠易激综合征肝郁脾虚证型肠道菌群-ENS-MM串扰骨形态发生蛋白2集落刺激因子1

Keywords

irritable bowel syndrome with diarrhealiver stagnation and spleen deficiency syndromegut microbiota-ENS-MM crosstalkbone morphogenetic protein 2colony stimulating factor 1

references

SPERBER A D，DUMITRASCU D，FUKUDO S，et al. The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies：a Rome foundation working team literature review[J]. Gut，2017，66（6）：1075-1082.

熊理守，陈旻湖，陈惠新，等. 社区人群中肠易激综合征的症状学特征[J]. 胃肠病学，2004，9（5）：277-279.

XIONG L S，CHEN M H，CHEN H X，et al. Symptomatologic characteristics of irritable bowel syndrome in community population[J]. Chin J Gastroenterol，2004，9（5）：277-279.

中华医学会消化病学分会胃肠功能性疾病协作组，中华医学会消化病学分会胃肠动力学组. 2020年中国肠易激综合征专家共识意见[J]. 中华消化杂志，2020，40（12）：803-818.

Collaborative Group of Gastrointestinal Functional Di- seases，Chinese Society of Gastroenterology， Gastrointestinal Dynamics Group，Chinese Society of Gastroentero- logy. Chinese expert consensus of irritable bowel syndrome in 2020[J]. Chin J Dig，2020，6（12）：803-818.

MULLER P A，KOSCSÓ B，RAJANI G M，et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility[J]. Cell，2014，158（5）：1210.

张声生，魏玮，杨俭勤. 肠易激综合征中医诊疗专家共识意见：2017[J]. 中医杂志，2017，58（18）：1614-1620.

ZHANG S S，WEI W，YANG J Q. Consensus opinion of Chinese medicine diagnosis and treatment experts on irritable bowel syndrome：2017[J]. J Tradit Chin Med，2017，58（18）：1614-1620.

李夏，王凤云，吴皓萌，等. 基于脑-肠互动功能探讨痛泻要方治疗腹泻性肠易激综合征机制的研究进展[J]. 中国实验方剂学杂志，2020，26（20）：229-234.

LI X，WANG F Y，WU H M，et al. Research progress on mechanism of Tongxie yaofang in treating diarrhea-predominate irritable bowel syndrome based on brain-gut interaction function[J]. Chin J Exp Tradit Med Formulae，2020，26（20）：229-234.

张北华，王微，王凤云，等. 痛泻要方干预腹泻型肠易激综合征肝郁脾虚证模型大鼠的效应评价[J]. 中华中医药杂志，2018，33（10）：4341-4346.

ZHANG B H，WANG W，WANG F Y，et al. Effects of Tongxie yaofang in treating IBS-D rats with syndrome of stagnation of liver qi and spleen deficiency[J]. China J Tradit Chin Med Pharm，2018，33（10）：4341-4346.

赵迎盼，唐旭东，卞兆祥，等. IBS-D肝郁脾虚型病证症结合大鼠模型的建立与评价的初步研究[J]. 中国中西医结合杂志，2013，33（11）：1507-1514.

ZHAO Y P，TANG X D，BIAN Z X，et al. Preliminary study of establishing and assessing IBS-D model rats of gan stagnation and pi deficiency syndrome[J]. Chin J Integr Tradit West Med，2013，33（11）：1507-1514.

AL-CHAER E D，KAWASAKI M，PASRICHA P J. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development[J]. Gastroenterology，2000，119（5）：1276-1285.

LI Y F，GONG X L，CHEN S X，et al. Deviations in the gut microbiota of neonates affected by maternal group B Streptococcus colonization[J]. BMC Microbiol，2021，21（1）：140.

程健，余莹，何君君. 腹泻型肠易激综合征中医“肝郁脾虚” 本质的探讨与思考[J]. 中华中医药杂志，2020，35（11）：5698-5703.

CHENG J，YU Y，HE J J. Discussion and consideration on the essence of ‘stagnation of liver qi and spleen deficiency’ in diarrhea-predominant irritable bowel syndrome[J]. China J Tradit Chin Med Pharm，2020，35（11）：5698-5703.

STAUDACHER H M，WHELAN K. Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet：probiotics，prebiotics and the low FODMAP diet[J]. Proc Nutr Soc，2016，75（3）：306-318.

FURNESS J B. The enteric nervous system and neuroga- stroenterology[J]. Nat Rev Gastroenterol Hepatol，2012，9（5）：286-294.

REGO S L，RAGHAVAN S，ZAKHEM E，et al. Enteric neural differentiation in innervated，physiologically functional，smooth muscle constructs is modulated by bone morphogenic protein 2 secreted by sphincteric smooth muscle cells[J]. J Tissue Eng Regen Med，2017，11（4）：1251-1261.

SCHNEIDER K M，BLANK N，ALVAREZ Y，et al. The enteric nervous system relays psychological stress to intestinal inflammation[J]. Cell，2023，186（13）：2823-2838.e20.

XIAO L，LIU Q，LUO M，et al. Gut microbiota-derived metabolites in irritable bowel syndrome[J]. Front Cell Infect Microbiol，2021，11：729346.

MOSSER D M，HAMIDZADEH K，GONCALVES R. Macrophages and the maintenance of homeostasis[J]. Cell Mol Immunol，2021，18（3）：579-587.

ZHAO Y，WU J F，LI J V，et al. Gut microbiota composition modifies fecal metabolic profiles in mice[J]. J Proteome Res，2013，12（6）：2987-2999.

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痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 Δ

Mechanism of Tongxie yaofang reducing colon hypermotility in IBS-D rats by regulating gut microbiota-ENS-MM crosstalk

DOI：10.6039/j.issn.1001-0408.2024.13.11

摘要

Abstract

关键词

Keywords

references

痛泻要方通过调控肠道菌群-ENS-MM串扰减轻IBS-D结肠运动亢进的机制研究 ^Δ