孙成宏;李翔子;肖贺;张丽;赵云;姚景春;张贵民;
SUN Cheng-hong;LI Xiang-zi;XIAO He;ZHANG Li;ZHAO Yun;YAO Jing-chun;ZHANG Gui-min;Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd.;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine;Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine;

• 1:鲁南制药集团股份有限公司新药药理中心
• 2:中药制药共性技术国家重点实验室
• 3:临沂市天然药物免疫药理毒理(企业)重点实验室

摘要(Abstract)：

用代谢组学方法分析首荟通便胶囊(SHTB)对慢传输型便秘小鼠结肠组织内源性代谢产物的影响,探讨SHTB治疗便秘的机制。ICR小鼠按体质量随机分为正常组、模型组、SHTB组。灌胃复方地芬诺酯建立慢传输型便秘模型,观察碳墨汁推进率、首次排便时间和12 h排便粒数。取结肠,阿利新蓝和过碘酸雪夫(AB-PAS)染色观察黏液细胞。超高效液相色谱-四极杆/静电场轨道阱高分辨质谱联用仪(UHPLC-ESI-QE-Orbitrap-MS)检测结肠组织差异代谢物,分析可能的代谢通路。结果表明,SHTB明显缩短便秘小鼠首次排便时间和排便数量,增加肠蠕动和结肠黏膜层黏液细胞数量。代谢组学研究显示,与正常组相比,模型组结肠共发现左旋尿嘧啶、N6,N6,N6-三甲基-L-赖氨酸、L-甲酰基鸟氨酸、N6-乙酰基-L-赖氨酸、L-苯丙氨酸、苯乙醛、黄嘌呤、胸苷、甘氨酰-L-亮氨酸、L-半胱氨酸、(R)-1-氨基丙烷-2-醇、脱氧胞苷、γ-谷氨酰-γ-氨基丁醛、D-半乳糖、L-精氨酸、L-脯氨酸、丙酮酸等17个代谢差异物。SHTB组这些代谢差异物有向正常水平回调的趋势。因此推测SHTB治疗慢性传输性便秘可能与调节苯丙氨酸代谢,苯丙氨酸、酪氨酸和色氨酸生物合成,精氨酸和脯氨酸代谢,半胱氨酸和蛋氨酸代谢,酪氨酸代谢,丙酮酸代谢,糖酵解,嘧啶代谢,精氨酸生物合成,三羧酸循环和半乳糖代谢等代谢通路有关。
The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.

关键词(KeyWords)： 首荟通便胶囊;便秘;结肠组织;代谢差异物;代谢通路
Shouhui Tongbian Capsules;constipation;colon tissue;differential metabolites;metabolic pathways

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2018ZX09201010)

作者(Author): 孙成宏;李翔子;肖贺;张丽;赵云;姚景春;张贵民;
SUN Cheng-hong;LI Xiang-zi;XIAO He;ZHANG Li;ZHAO Yun;YAO Jing-chun;ZHANG Gui-min;Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd.;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine;Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine;

Email:

DOI: 10.19540/j.cnki.cjcmm.20201116.401

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