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矢车菊素-3-O-葡萄糖苷通过抑制HS调节的AMPK/mTOR途径改善重症急性胰腺炎期间的结肠动力。

Cyanidin-3-O-Glucoside Improves Colonic Motility During Severe Acute Pancreatitis by Inhibiting the HS-Regulated AMPK/mTOR Pathway.

作者信息

Lian Wei, Chen Wensheng

机构信息

Department of Gastroenterology, Southwest Hospital of Army Medical University, Chongqing, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Aug 19;14:3385-3391. doi: 10.2147/DDDT.S256450. eCollection 2020.

Abstract

BACKGROUND

Cyanidin-3-O-glucoside (C3G) is an important anthocyanin that can modulate digestive system functioning. Inflammation associated with severe acute pancreatitis (SAP) induces HS production, which impairs the gastrointestinal (GI) system. We investigated the effects of C3G in attenuating SAP-associated colonic motility loss by examining the HS level and activity of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.

METHODS

A rat model of SAP was induced using sodium taurocholate, and the effect of C3G on colonic mobility, HS production, and the inflammatory response was investigated. AMPK/mTOR pathway changes were detected to assess the pathways by which HS influences colonic mobility in SAP-model rats. The mechanism underlying HS function was further examined by subjecting colonic muscle cells (CMCs) to C3G, SAP plasma and an AMPK activator.

RESULTS

Administering C3G improved colonic motility but suppressed the inflammatory response and HS production in the SAP-model rats, which was associated with inhibiting the AMPK/mTOR pathway. Furthermore, activating the AMPK/mTOR pathway in CMCs promoted inflammation but suppressed Ca2+ levels, even after administering C3G.

CONCLUSION

Administering C3G may improve SAP-associated colonic mobility by inhibiting the HS-mediated AMPK/mTOR pathway.

摘要

背景

矢车菊素 - 3 - O - 葡萄糖苷(C3G)是一种重要的花青素,可调节消化系统功能。与重症急性胰腺炎(SAP)相关的炎症会诱导硫酸乙酰肝素(HS)生成,进而损害胃肠(GI)系统。我们通过检测HS水平以及AMP激活的蛋白激酶(AMPK)/雷帕霉素哺乳动物靶蛋白(mTOR)通路的活性,研究了C3G在减轻与SAP相关的结肠动力丧失方面的作用。

方法

采用牛磺胆酸钠诱导建立大鼠SAP模型,研究C3G对结肠动力、HS生成及炎症反应的影响。检测AMPK/mTOR通路变化,以评估HS影响SAP模型大鼠结肠动力的途径。通过将结肠肌细胞(CMCs)分别暴露于C3G、SAP血浆和一种AMPK激活剂,进一步研究HS功能的潜在机制。

结果

给予C3G可改善SAP模型大鼠的结肠动力,但抑制炎症反应和HS生成,这与抑制AMPK/mTOR通路有关。此外,即使给予C3G后,激活CMCs中的AMPK/mTOR通路也会促进炎症反应,但会抑制钙离子水平。

结论

给予C3G可能通过抑制HS介导的AMPK/mTOR通路来改善与SAP相关的结肠动力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c0/7468407/bb541daa5438/DDDT-14-3385-g0001.jpg

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