摘要
目的研究芍药甘草汤(Shaoyao Gancao decoction,SGD)对炎症后肠易激综合征(post-inflammatory irritable bowel syndrome,PI-IBS)大鼠的干预作用,并基于代谢组学探讨其作用机制。方法18只SD雄性大鼠随机分为正常组、模型组(PI-IBS)及SGD组,每组6只。采用2,4,6-三硝基苯磺酸灌肠法制备大鼠PI-IBS模型,SGD组在造模后第28天开始灌胃给药SGD 25 g/(kg·d),连续14 d。正常组和模型组大鼠灌胃给予相应体积的生理盐水。以疾病活动指数(DAI)、内脏痛阈值评分、大鼠结肠组织病理形态学改变及结肠病理损伤评分评估SGD对PI-IBS大鼠的干预作用。利用超高效液相色谱-串联四级杆飞行时间二级质谱联用(UPLC-Q/TOF-MS)和代谢组学方法鉴定血浆差异代谢物并经MetaboAnalyst数据库分析代谢通路。结果与正常组相比,PI-IBS组大鼠DAI指数明显升高(P<0.05),内脏痛阈值评分明显降低(P<0.05),结肠黏膜严重受损并伴有大量炎症细胞浸润,结肠病理损伤评分明显增加(P<0.05)。与PI-IBS组相比,SGD组大鼠DAI指数明显降低(P<0.05),内脏痛阈值评分明显升高(P<0.05),结肠组织损伤改善且黏膜炎症明显缓解,结肠病理损伤评分明显降低(P<0.05)。正常组和PI-IBS组大鼠血浆共鉴定出30个差异代谢物,SGD可显著回调14个差异代谢物的变化,主要富集于嘧啶代谢、丙氨酸,天冬氨酸和谷氨酸代谢、嘌呤代谢、乙醛酸和二羧酸的代谢和三羧酸(TCA)循环等代谢通路。结论SGD干预PI-IBS大鼠的机制可能与嘧啶代谢,丙氨酸、天冬氨酸和谷氨酸代谢,嘌呤代谢,乙醛酸和二羧酸的代谢和三羧酸循环等代谢通路有关。
Objective To study the intervention effect of Shaoyao Gancao decoction(SGD)on post-inflammatory irritable bowel syndrome(PI-IBS)in rats,and explore its mechanism based on metabolomics.Methods Eighteen male SD rats were randomly divided into normal group,model group(PI-IBS)and SGD group,with 6 rats in each group.PI-IBS rat model was prepared by 2,4,6-trinitrobenzene sulfonic acid enema method.The rats in SGD group were given SGD 25 g/(kg•d)by intragastric administration for conse-cutive 14 d from the 28th day after modeling.The rats in normal group and model group were given a corresponding volume of normal saline by gavage.Disease activity index(DAI),visceral pain threshold score,colonic histopathological changes and colonic pathological damage score were used to evaluate the intervention effect of SGD on PI-IBS in rats.UPLC-Q/TOF-MS and metabonomics methods were used to identify plasma differential metabolism and the metabolic pathways were analyzed by MetaboAnalyst database.Results Compared with normal group,DAI index of rats was significantly increased in PI-IBS group(P<0.05),the visceral pain threshold score was significantly reduced(P<0.05),the colonic mucosa was severely damaged with a large number of inflammatory cell infiltration,and the colonic pathological damage score was significantly increased(P<0.05).Compared with PI-IBS group,DAI index of rats was significantly reduced in SGD group(P<0.05),the visceral pain threshold score was significantly increased(P<0.05),the colon tissue damage was improved and the mucosal inflammation was significantly alleviated,and the colon pathological damage score was significantly reduced(P<0.05).A total of 30 differential metabolites were identified in the plasma of normal rats and PI-IBS rats,and SGD significantly reversed the changes of 14 differential metabolites,which were mainly concentrated in metabolic pathways such as pyrimidine metabolism,alanine,aspartic acid and glutamate acid metabolism,purine metabolism,glyoxylic acid and dicarboxylic acid metabolism,and tricarboxylic acid(TCA)cycle.Conclusion The mechanism of SGD intervention in PI-IBS rats may be related to metabolic pathways such as pyrimidine metabolism,alanine,aspartic acid and glutamic acid metabolism,purine metabolism,glyoxylic acid and dicarboxylic acid metabolism,and TCA cycle.
作者
武蓓
常壮鹏
邓贵凤
邵云云
WU Bei;CHANG Zhuangpeng;DENG Guifeng;SHAO Yunyun(Department of Pharmacy,Second Hospital of Shanxi Medical University,Taiyuan 030001,China;School of Pharmacy,Shanxi Medical University)
出处
《山西医科大学学报》
CAS
2021年第5期605-611,共7页
Journal of Shanxi Medical University
基金
山西省卫生健康委科研课题(2015046)。
关键词
芍药甘草汤
炎症后肠易激综合征
代谢组学
Shaoyao Gancao decoction
post-inflammatory irritable bowel syndrome
metabolomics
