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基于超高效液相色谱-电喷雾电离-四级杆-轨道阱质谱联用技术的首荟通便胶囊治疗慢传输型便秘的代谢组学研究

[Metabonomics study of Shouhui Tongbian Capsules in slow transit constipation based on UPLC-ESI-QE-Orbitrap-MS].

作者信息

Sun Cheng-Hong, Li Xiang-Zi, Xiao He, Zhang Li, Zhao Yun, Yao Jing-Chun, Zhang Gui-Min

机构信息

Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd. Linyi 276006, China State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine Linyi 276006 China Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine Linyi 276006, China.

Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd. Linyi 276006, China Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine Linyi 276006, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):532-538. doi: 10.19540/j.cnki.cjcmm.20201116.401.

Abstract

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.

摘要

采用代谢组学方法分析寿辉通便胶囊(SHTB)对慢传输型便秘小鼠结肠组织内源性代谢产物的影响,以探讨其治疗便秘的作用机制。将ICR小鼠按体重随机分为正常组、模型组和SHTB组。给予小鼠地芬诺酯建立慢传输型便秘模型。观察小鼠炭末推进率、首次排便时间及12 h内排便颗粒数。分离小鼠结肠组织,采用高碘酸希夫和阿尔辛蓝(AB-PAS)染色检测黏液细胞。运用超高效液相色谱电喷雾电离轨道阱串联质谱(UPLC-ESI-Orbitrap-MS/MS)技术表征组织代谢差异,筛选出结肠组织中潜在的差异代谢产物及可能的代谢途径。结果表明,与模型小鼠相比,SHTB可显著缩短首次排便时间和排便次数,并增加结肠黏膜的肠蠕动次数和黏液细胞数量。代谢组学结果显示,与正常组相比,结肠组织中共发现并鉴定出17种潜在生物标志物,包括L-犬尿氨酸、N6,N6,N6-三甲基-L-赖氨酸、L-甲酰犬尿氨酸、N6-乙酰-L-赖氨酸、L-苯丙氨酸、苯乙醛、黄嘌呤核苷、胸腺嘧啶核苷、甘氨酰-L-亮氨酸、胱硫醚、(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-脯氨酸和丙酮酸。经SHTB治疗后,这些代谢差异趋于恢复正常水平。因此,可以得出结论,SHTB对慢性传输型便秘的治疗作用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、半胱氨酸和甲硫氨酸代谢、酪氨酸代谢、精氨酸生物合成、丙酮酸代谢、糖酵解、嘧啶代谢、三羧酸循环和半乳糖代谢有关。

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