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整合转录组学和代谢组学分析揭示了缓溃乐混悬液对三硝基苯磺酸诱导的溃疡性结肠炎的分子机制。

Integrative transcriptomic and metabonomic profiling analyses reveal the molecular mechanism of Chinese traditional medicine huankuile suspension on TNBS-induced ulcerative colitis.

机构信息

Department of Biochemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong 637100, Sichuan Province, China.

出版信息

Aging (Albany NY). 2021 Feb 1;13(4):5087-5103. doi: 10.18632/aging.202427.

Abstract

This study aimed to investigate the therapeutic mechanism of Huankuile suspension (HKL), a typical traditional Chinese medicine, on ulcerative colitis (UC) in a rat model. UC model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. Then, the rats were randomly divided into three groups: water treated group, HKL treated group and 5- amino salicylic acid (5-ASA) treated group. After 7 days treatment, the histological score in the HKL treated group was comparable with those in the control group. qRT-PCR and western blot demonstrated that HKL could significantly decreased pro-inflammatory cytokines, including , and , while having less effect on anti-inflammatory cytokines, including and . Transcriptomic analysis identified 670 differentially expressed genes (DEGs) between HKL treated UC rats and water treated UC rats. These DEGs were mostly related with immune response. Besides, metabonomic profile revealed 136 differential metabolites which were significantly enriched in "pyrimidine metabolism", "glutathione metabolism", "purine metabolism" and "citrate cycle". Finally, integrated analysis revealed that metabonomic pathways including "steroid hormone biosynthesis", "pyrimidine metabolism", "purine metabolism", and "glutathione metabolism" were altered by HKL at both transcriptomic and metabonomic levels. HKL could inhibit inflammation and regulate bile metabolism, pyrimidine metabolism, purine metabolism, glutathione metabolism and citrate cycle.

摘要

本研究旨在探讨缓溃乐混悬液(HKL)——一种典型的中药——对溃疡性结肠炎(UC)大鼠模型的治疗机制。通过 2,4,6-三硝基苯磺酸(TNBS)灌肠法建立 UC 模型。然后,将大鼠随机分为三组:水治疗组、HKL 治疗组和 5-氨基水杨酸(5-ASA)治疗组。治疗 7 天后,HKL 治疗组的组织学评分与对照组相当。qRT-PCR 和 Western blot 表明,HKL 可显著降低促炎细胞因子,包括 TNF-α、IL-1β 和 IL-6,而对抗炎细胞因子,如 IL-10 和 TGF-β,影响较小。转录组分析鉴定出 HKL 治疗 UC 大鼠和水治疗 UC 大鼠之间的 670 个差异表达基因(DEGs)。这些 DEGs 主要与免疫反应有关。此外,代谢组学分析揭示了 136 个差异代谢物,这些代谢物在“嘧啶代谢”、“谷胱甘肽代谢”、“嘌呤代谢”和“柠檬酸循环”中显著富集。最后,综合分析表明,代谢组学途径包括“甾体激素生物合成”、“嘧啶代谢”、“嘌呤代谢”和“谷胱甘肽代谢”,在转录组和代谢组水平均受 HKL 调节。HKL 可抑制炎症反应,调节胆汁代谢、嘧啶代谢、嘌呤代谢、谷胱甘肽代谢和柠檬酸循环。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1739/7950284/6bfebcaca27a/aging-13-202427-g001.jpg

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