浏览全部资源
扫码关注微信
痛泻要方通过调控结肠TPH1、SERT及肠道菌群改善腹泻型肠易激综合征症状
Improvement effects of Tongxie yaofang on irritable bowel syndrome with diarrhea by regulating colonic TPH1， SERT and intestinal flora
- 中国药房 2024年35卷第18期 页码：2238-2245
- 作者机构：
1.川北医学院附属医院中西医结合肛肠科，四川 南充 637000
2.川北医学院临床医学院，四川 南充 637000
- 作者简介：
医师，硕士。研究方向：中西医治疗肛肠疾病。E-mail：ruisun17@163.com
教授，博士。研究方向：中西医治疗肛肠疾病。E-mail：wzj549nc@126.com
- 基金信息：四川省自然科学基金项目(S22018)
DOI：10.6039/j.issn.1001-0408.2024.18.09
中图分类号： R965;R574.4纸质出版日期：2024-09-30，
收稿日期：2024-03-09，
修回日期：2024-07-10，
- 稿件说明：
移动端阅览
孙锐,罗婷,谢海洋等.痛泻要方通过调控结肠TPH1、SERT及肠道菌群改善腹泻型肠易激综合征症状 Δ[J].中国药房,2024,35(18):2238-2245.
SUN Rui,LUO Ting,XIE Haiyang,et al.Improvement effects of Tongxie yaofang on irritable bowel syndrome with diarrhea by regulating colonic TPH1， SERT and intestinal flora[J].ZHONGGUO YAOFANG,2024,35(18):2238-2245.
孙锐,罗婷,谢海洋等.痛泻要方通过调控结肠TPH1、SERT及肠道菌群改善腹泻型肠易激综合征症状 Δ[J].中国药房,2024,35(18):2238-2245. DOI： 10.6039/j.issn.1001-0408.2024.18.09.
SUN Rui,LUO Ting,XIE Haiyang,et al.Improvement effects of Tongxie yaofang on irritable bowel syndrome with diarrhea by regulating colonic TPH1， SERT and intestinal flora[J].ZHONGGUO YAOFANG,2024,35(18):2238-2245. DOI： 10.6039/j.issn.1001-0408.2024.18.09.
摘要
目的
2
探讨痛泻要方调控结肠色氨酸羟化酶1（TPH1）、5-羟色胺转运体（SERT）及肠道菌群对腹泻型肠易激综合征（IBS-D）大鼠症状的影响。
方法
2
将42只SD大鼠随机分为对照组（7只）和造模组（35只）。造模组大鼠采用0.45 g/L的番泻叶药液[10 mL/（kg·d）]灌胃联合慢性不可预知性应激的方法建立IBS-D模型。将造模成功的35只大鼠随机分为模型组、匹维溴铵组[15 mg/（kg·d）]和痛泻要方低、中、高剂量组[3.75、7.5、15 g/（kg·d），以生药量计]，每组7只。各药物组灌胃相应药液，每天1次，连续10 d。分别于造模前、造模后给药前、末次药物干预后评估各组大鼠的一般情况和体重变化情况；分别于造模后给药前、末次药物干预后检测其腹泻指数、内脏敏感性，观察其结肠组织病理变化，检测其结肠组织中5-羟色胺（5-HT）水平及蛋白表达情况和TPH1、SERT蛋白及mRNA的表达水平，并分析大鼠粪便样品中肠道菌群的多样性及物种组成变化。
结果
2
各组大鼠结肠组织均未见明显病理改变。与模型组比较，各药物组大鼠一般情况改善；痛泻要方中、高剂量组大鼠的日均体重增长量显著增加，腹泻指数、内脏敏感性和结肠组织5-HT、TPH1表达均显著降低或减少，结肠组织SERT表达显著增加（
P
＜0.05或
P
＜0.01）；痛泻要方低剂量组大鼠腹泻指数、结肠TPH1蛋白表达、结肠5-HT蛋白阳性率均显著降低，SERT mRNA表达显著增加（
P
＜0.05）；痛泻要方的干预效果有剂量依赖趋势。与模型组比较，痛泻要方高剂量组大鼠的Chao1指数、Shannon指数均显著降低（
P
＜0.05或
P
＜0.01），厚壁菌门、乳酸杆菌属等有益菌显著增加，变形菌门、大肠杆菌属-志贺氏杆菌属、
Rikenellaceae
_RC9_gut_group等致病菌显著减少（
P
＜0.05或
P
＜0.01）。
结论
2
痛泻要方可通过抑制结肠组织中TPH1的表达并上调SERT的表达来降低5-HT水平、改善肠道菌群紊乱，从而改善IBS-D大鼠症状。
Abstract
OBJECTIVE
2
To investigate the effects of Tongxie yaofang （TXYF） on the symptoms of rats with irritable bowel syndrome with diarrhea （IBS-D） by regulating colonic tryptophan hydroxylase 1 （TPH1）， serotonin transporter （SERT） and intestinal flora.
METHODS
2
Forty-two SD rats were randomly divided into control group （7 rats） and modeling group （35 rats）. In modeling group， rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution [10 mL/（kg·d）] combined with chronic unpredictable stimulation. Thirty-five successfully modeled rats were randomly divided into model group， pinaverium bromide group [15 mg/（kg·d）] and TXYF low-dose， medium-dose and high-dose groups [3.75、7.5、15 g/（kg·d）， calculated by crude drug]， with 7 rats in each group. Each administration group was orally administered the corresponding drug， once a day， for 10 consecutive days. The general condition and weight changes of each group of rats were compared before modeling， after modeling and before administration， after the last drug intervention； the diarrhea index and visceral sensitivity were detected， and pathological changes of colon tissue were observed after modeling and before administration， after the last drug intervention. The level and expression of 5-hydroxytryptamine （5-HT）， protein and mRNA expressions of TPH1 and SERT were determined in colon tissue. The diversity and structural changes of fecal intestinal flora of rats were analyzed.
RESULTS
2
There was no significant change in colon histopathology in each group. Compared with model group， the general condition of rats in each medication group improved. The daily body weight gain of rats was significantly increased， while diarrhea index， visceral sensitivity， the expressions of 5-HT and TPH1 in colon tissue were significantly decreased； SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups （
P
＜0.05 or
P
＜0.01）. The diarrhea index， colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly （
P
＜0.05）. There was a dose-dependent trend in the effect of TXYF. Compared with model group， Chao1 index and Shannon index of the rats in TXYF high-dose group were significantly decreased （
P
＜0.05 or
P
＜0.01）， the beneficial bacteria such as Firmicutes and
Lactobacillus
increased significantly， while the pathogenic bacteria such as Proteobacteria，
Escherichia
-
Shigella
and
Rikenellaceae
_RC9_gut_group decreased significantly （
P
＜0.05 or
P
＜0.01）.
CONCLUSIONS
2
TXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue， thus promoting the symptoms of IBS-D rats.
关键词
痛泻要方腹泻型肠易激综合征5-羟色胺色氨酸羟化酶15-羟色胺转运蛋白肠道菌群
Keywords
irritable bowel syndrome with diarrhea5-hydroxytryptaminetryptophan hydroxylase 1serotonin transporterintestinal flora
references
DROSSMAN D A，HASLER W L. Rome Ⅳ-functional GI disorders：disorders of gut-brain interaction[J]. Gastroenterology，2016，150（6）：1257-1261.
LI J C，CUI H T，CAI Y Z，et al. Tong-xie-yao-fang regulates 5-HT level in diarrhea predominant irritable bowel syndrome through gut microbiota modulation[J]. Front Pharmacol，2018，9：1110.
ZHANG F，XIANG W，LI C Y，et al. Economic burden of irritable bowel syndrome in China[J]. World J Gastroenterol，2016，22（47）：10450-10460.
FORD A C，LACY B E，TALLEY N J. Irritable bowel syndrome[J]. N Engl J Med，2017，376（26）：2566-2578.
CHEN M J，RUAN G C，CHEN L，et al. Neurotransmitter and intestinal interactions：focus on the microbiota-gut-brain axis in irritable bowel syndrome[J]. Front Endocrinol，2022，13：817100.
MOORE N A，SARGENT B J，MANNING D D，et al. Partial agonism of 5-HT3 receptors：a novel approach to the symptomatic treatment of IBS-D[J]. ACS Chem Neurosci，2013，4（1）：43-47.
FRANCESCANGELI J，KARAMCHANDANI K，POWELL M，et al. The serotonin syndrome：from molecular mechanisms to clinical practice[J]. Int J Mol Sci，2019，20（9）：2288.
李潇潇，卢圣锋，朱冰梅，等. 5-HT与肠道菌群及其在肠-脑相关疾病中的作用研究进展[J]. 中国康复医学杂志，2019，34（1）：116-119.
LI X X，LU S F，ZHU B M，et al. Research progress on 5-HT and intestinal flora and its role in gut-brain related diseases[J]. Chin J Rehabilitat Med，2019，34（1）：116-119.
王栩芮，傅文斌，孙弋淇，等. 痛泄要方缓解肝郁脾虚证腹泻型肠易激综合征患者内脏高敏的临床疗效[J]. 中国实验方剂学杂志，2022，28（9）：97-102.
WANG X R，FU W B，SUN Y Q，et al. Clinical efficacy of Tongxie yaofang on diarrhea-predominant irritable bowel syndrome（IBS-D）patients with liver depression and spleen deficiency[J]. Chin J Exp Tradit Med Formulae，2022，28（9）：97-102.
孙羽中. 痛泻要方调控IBS肝郁脾虚证大鼠海马、皮质、下丘脑TPH和SERT的实验研究[D]. 太原：山西中医药大学，2018.
SUN Y Z. Experimental study on treatment of TPH and SERT in hippocampus，cortex and hypothalamus of rats with IBS deficiency of spleen and deficiency syndrome by Tongxie yaofang[D].Taiyuan：Shangxi University of Chinese Medicine，2018.
仝理，吴立斌，李难，等. 基于5-羟色胺信号通路探讨艾灸治疗腹泻型肠易激综合征的机制[J]. 针刺研究，2020，45（7）：535-540.
TONG L，WU L B，LI N，et al. Moxibustion relieves abdominal hypersensitivity and diarrhea by regulating colonic 5-hydroxytryptamine signaling pathway in rats with diarrhea type irritable bowel syndrome[J]. Acupunct Res，2020，45（7）：535-540.
HOU Y J，ZHAO Y，JIANG H L，et al. Maintenance of intestinal homeostasis in diarrhea-predominant irritable bowel syndrome by electroacupuncture through submucosal enteric glial cell-derived S-nitrosoglutathione[J]. Front Physiol，2022，13：917579.
张扬雨. 匹维溴铵与安肠汤干预IBS-D大鼠模型的血清代谢组学对比研究[D]. 南宁：广西中医药大学，2023.
ZHANG Y Y. Comparative serum metabolomic study of pinaverium bromide and Anchang decoction intervention in rat model of IBS-D[D]. Nanning：Guangxi University of Chinese Medicine，2023.
陈奇. 中药药理研究方法学[M]. 3版. 北京：人民卫生出版社，2011：135-136.
CHEN Q. Research methods in pharmacology of Chinese materia medica[M]. 3rd edition. Beijing：People’s Medical Publishing House，2011：135-136.
LI X M，REN K Y，HONG X J，et al. Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome[J]. J Gastroenterol Hepatol，2022，37（10）：1963-1974.
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.
CHAO A，BUNGE J. Estimating the number of species in a stochastic abundance model[J]. Biometrics，2002，58（3）：531-539.
HILL T C J，WALSH K A，HARRIS J A，et al. Using ecological diversity measures with bacterial communities[J]. FEMS Microbiol Ecol，2003，43（1）：1-11.
柯水芳，陆敏. 腹泻型肠易激综合征中医药治疗研究进展[J]. 光明中医，2017，32（4）：612-614.
KE S F，LU M. Research progress of Chinese medicine in the treatment of diarrhea predominant irritable bowel syndrome[J]. Guangming J Chin Med，2017，32（4）：612-614.
赵清玉，张淼，赵文静，等. 痛泻要方物质基础及药理作用研究进展[J]. 中国实验方剂学杂志，2023，29（8）：237-245.
ZHAO Q Y，ZHANG M，ZHAO W J，et al. Material basis and pharmacological action of Tongxie yaofang：a review[J]. Chin J Exp Tradit Med Formulae，2023，29（8）：237-245.
MARGOLIS K G，CRYAN J F，MAYER E A. The microbiota-gut-brain axis：from motility to mood[J]. Gastroenterology，2021，160（5）：1486-1501.
BONETTO S，FAGOONEE S，BATTAGLIA E，et al. Recent advances in the treatment of irritable bowel syndrome[J]. Pol Arch Intern Med，2021，131（7/8）：709-715.
KATSUMATA R，SHIOTANI A，MURAO T，et al. The TPH1 rs211105 gene polymorphism affects abdominal symptoms and quality of life of diarrhea-predominant irritable bowel syndrome[J]. J Clin Biochem Nutr，2018，62（3）：270-276.
GERSHON M D，TACK J. The serotonin signaling system：from basic understanding to drug development for functional GI disorders[J]. Gastroenterology，2007，132（1）：397-414.
CROWELL M D. Role of serotonin in the pathophy-siology of the irritable bowel syndrome[J]. Br J Pharmacol，2004，141（8）：1285-1293.
LEE S M，KIM N，YOON H，et al. Compositional and functional changes in the gut microbiota in irritable bowel syndrome patients[J]. Gut Liver，2021，15（2）：253-261.
ZHUANG X J，TIAN Z Y，LI L，et al. Fecal microbiota alterations associated with diarrhea-predominant irritable bowel syndrome[J]. Front Microbiol，2018，9：1600.
SHANG L J，LIU H B，YU H T，et al. Core altered microorganisms in colitis mouse model：a comprehensive time-point and fecal microbiota transplantation analysis[J]. Anti-biotics，2021，10（6）：643.
YE X，HUANG D，DONG Z X，et al. FXR signaling-mediated bile acid metabolism is critical for alleviation of cholesterol gallstones by Lactobacillus strains[J]. Microbiol Spectr，2022，10（5）：e0051822.
LIANG H Y，SONG H，ZHANG X J，et al. Metformin attenuated sepsis-related liver injury by modulating gut microbiota[J]. Emerg Microbes Infect，2022，11（1）：815-828.
RIZZATTI G，LOPETUSO L R，GIBIINO G，et al. Proteobacteria：a common factor in human diseases[J]. Biomed Res Int，2017，2017：9351507.
ZHANG X M，CHEN S B，ZHANG M，et al. Effects of fermented milk containing Lacticaseibacillus paracasei strain Shirota on constipation in patients with depression：a randomized，double-blind，placebo-controlled trial[J]. Nutrients，2021，13（7）：2238.
CHAVES FILHO A J M，LIMA C N C，VASCONCELOS S M M，et al. IDO chronic immune activation and tryptophan metabolic pathway：a potential pathophysiological link between depression and obesity[J]. Prog Neuropsychopharmacol Biol Psychiatry，2018，80（Pt C）：234-249.
AGUS A，PLANCHAIS J，SOKOL H. Gut microbiota regulation of tryptophan metabolism in health and disease[J]. Cell Host Microbe，2018，23（6）：716-724.
ESMAILI A，NAZIR S F，BORTHAKUR A，et al. Enteropathogenic Escherichia coli infection inhibits intestinal serotonin transporter function and expression[J]. Gastroenterology，2009，137（6）：2074-2083.
ROAGER H M，LICHT T R. Microbial tryptophan catabolites in health and disease[J]. Nat Commun，2018，9（1）：3294.
0
浏览量
0
下载量
0
CSCD
- 网络PDF下载
- WORD下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 地址：重庆市渝中区大坪正街129号四环大厦8层 邮编：400042
- 技术支持由北京北大方正电子有限公司提供 渝ICP备15012710号
公网安备50010302001817 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies