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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
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| 篇名： | 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 |
| TITLE： | Improvement effects of Tongxie yaofang on irritable bowel syndrome with diarrhea by regulating colonic TPH1，SERT and intestinal flora |
| 摘要： | 目的 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0.45g/L的番泻叶药液[10mL/（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[15mg/（kg·d）]和痛泻要方低、中、高剂量组[3.75、7.5、15g/（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10d。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，SERTmRNA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 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 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 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 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. |
| 期刊： | 2024年第35卷第18期 |
| 作者： | 孙锐；罗婷；谢海洋；张乐；文婧；黄山；吴至久 |
| AUTHORS： | SUN Rui，LUO Ting，XIE Haiyang，ZHANG Le，WEN Jing，HUANG Shan，WU Zhijiu |
| 关键字： | 痛泻要方；腹泻型肠易激综合征；5-羟色胺；色氨酸羟化酶1；5-羟色胺转运蛋白；肠道菌群 |
| KEYWORDS： | Tongxie yaofang； irritable bowel syndrome with diarrhea； 5-hydroxytryptamine； tryptophan hydroxylase 1； |
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