IBS-D诊断及治疗的潜在靶点——脂质、类花生酸及胆汁酸类差异代谢物  

Potential targets for diagnosis and treatment of IBS-D,differential metabolites of lipids,eicosanoids and bile acids

作　　者：于官正 李鸿 涂星 张燕 杨宝 聂娟 YU Guanzheng;LI Hong;TU Xing△;ZHANG Yan;YANG Bao;NIE Juan(Chinese Medicinal Materials Products Quality Supevision and Inspection Center in Wuling Mountainous Area,Enshi 445000,China;Health Science Center,Hubei Minzu University,Enshi 445000,China)

机构地区：[1]湖北民族大学武陵山中药材检验检测中心,湖北恩施445000 [2]湖北民族大学医学部,湖北恩施445000

出　　处：《中国病理生理杂志》2023年第8期1467-1474,共8页Chinese Journal of Pathophysiology

基　　金：湖北省教育厅科学技术研究项目(No.B2022097);湖北民族大学2022年揭榜挂帅资助项目(No.JB22003);湖北省科技厅科学技术研究项目(No.2022BCE043);恩施州科技项目技术支撑类重点项目(No.D20220065)。

摘　　要：目的:探讨多因素(母婴分离联合束缚应激与醋酸直肠刺激及番泻叶灌胃)复合诱导腹泻型肠易激综合征(IBS-D)大鼠模型结肠组织内源性差异代谢物,寻找IBS-D诊断和治疗的潜在作用环节和靶点。方法:将SD大鼠随机分为正常(normal)组与模型(model)组,以母婴分离联合束缚应激与直肠醋酸刺激及番泻叶灌胃诱导IBS-D大鼠模型。对大鼠进行一般行为学观察、粪便Bristol评分、粪便含水量测定及腹部回缩反射(AWR)评分压力阈值并观察肠组织病理变化;采用超高效液相色谱-串联三重四极杆飞行时间质谱(UPLC-Q-TOF-MS)技术测定大鼠肠组织内源性代谢物的表达,通过主成分分析(PCA)、正交偏最小二乘法-判别分析(OPLS-DA)筛选潜在差异代谢物,MetaboAnalyst 5.0进行代谢通路分析。结果:与正常组比较,模型组大鼠一般行为学评分与AWR评分压力阈值显著降低(P<0.05),粪便Bristol评分及粪便含水量显著升高(P<0.05),结肠组织上皮细胞未见脱落,无炎症细胞浸润,无水肿,肌纤维结构紧密,杯状细胞大小整齐,隐窝和绒毛无消融现象。在大鼠结肠组织中鉴定出76个差异代谢物,包括磷脂酰乙醇胺、前列腺素E1、胆酸等,与甘油磷脂代谢和醚脂代谢等代谢通路密切相关。结论:母婴分离联合束缚应激与直肠醋酸刺激及番泻叶灌胃多因素复合诱导的IBS-D大鼠模型具有典型的腹痛、腹泻等症状,且肠组织无病理学改变,高度拟合其临床特征。脂质、类花生酸及胆汁酸类代谢物在IBS-D大鼠中存在着明显的差异性调节,可能是其发病的潜在靶点及临床诊疗可筛选的潜在指标。AIM:To explore the endogenous differential metabolites in colon tissue of diarrhea-type irritable bowel syndrome(IBS-D)rats induced by multiple factors(maternal separation combined with restraint stress,acetic acid stimulation of rectum and folium sennae by intragastric administration),so as to search for the potential links and targets for the diagnosis and treatment of IBS-D.METHODS:SD rats were divided into control group and IBS-D(model)group randomly.The IBS-D rat were induced by maternal separation combined with restraint stress,acetic acid stimulation of rectum and folium sennae by intragastric administration.General behavioral observations,Bristol integral system,moisture of the feces and AWR score pressure threshold of rats were performed,and the pathological changes of intestinal tissues were observed by HE and AB-PAS.Endogenous metabolites in colon tissue was detected by UPLC-Q-TOF-MS and the endogenous differential metabolites were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis.The metabolic pathways were established by MetaboAnalyst 5.0 software.RESULTS:Comparing with control group,the general behavioral score and AWR score pressure threshold of rats in IBS-D group decreased significantly(P<0.05),while Bristol integral system and moisture of the feces increased significantly(P<0.05).There were not shed of epithelial cells in the colon tissue,no infiltration of inflammatory cells and edema.The structure of muscle fibers was compact,the size of goblet cells was neat,and there was no ablation of crypts and villi.Metabolomics analysis identified 76 different metabolites in rat intestinal tissues,including phosphatidyl ethanolamine,prostaglandin E1,cholic acid,etc.The main metabolic pathways involved were glycerophospholipid metabolism and ether lipid metabolism.CONCLUSION:The IBS-D rat model induced by maternal separation combined with restraint stress,acetic acid stimulation of rectum and folium sennae by intragastric administration showed typical symp

关 键 词：腹泻型肠易激综合征 代谢组学 超高效液相色谱-串联三重四极杆飞行时间质谱 脂质代谢 类花生酸类 胆汁酸类 

分 类 号：R363.2[医药卫生—病理学] R574[医药卫生—基础医学]