魔芋寡糖通过激活5-HT4R/cAMP/PKA/p-CREB通路缓解小鼠便秘

IF 1.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Guang-Jun Sun, Ming Li, Xiao-Yu Zhang, Jin-Shuang Liu, Ai-Zhen Lin, Qiong Cai
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引用次数: 0

摘要

背景:魔芋低聚糖(Konjac oligosaccharide, KOS)是通过酶、化学或物理处理降解魔芋葡甘露聚糖而产生的,已被发现具有通便作用。本研究旨在阐明KOS通便作用的机制。方法:对洛哌丁胺致便秘的5-羟色胺4受体(5-HT4R)敲除C57BL/6小鼠灌胃给予KOS,持续4周。治疗后,收集粪便、血液、小肠、结肠组织和肠道内容物。评估便秘相关参数、胃肠激素和Ca2+浓度。苏木精染色、伊红染色观察组织病理变化。免疫荧光染色、免疫印迹、免疫组化染色检测5-HT4R/环磷酸腺苷(cAMP)/蛋白激酶A (PKA)通路。用KOS和GR113808 (5-HT4R拮抗剂)处理离体平滑肌细胞(SMCs),倒置显微镜下观察形态学,α-SMA免疫荧光染色鉴定。通过CCK-8检测细胞活力。Western blotting检测SMCs中5-HT4R/cAMP/PKA/p-CREB通路活性。结果:KOS可减轻洛哌丁胺所致小鼠便秘。KOS在洛哌丁胺诱导的便秘小鼠中激活了5-HT4R/cAMP/PKA/p-CREB通路。在5-HT4R-/-小鼠中,KOS的保护作用明显减弱。KOS通过激活5-HT4R/cAMP/PKA/p-CREB信号通路促进SMCs的增殖。结论:KOS通过激活5-HT4R/cAMP/PKA/p-CREB信号通路改善洛哌丁胺所致便秘。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Konjac Oligosaccharide Alleviates Constipation in Mice via 5-HT4R/cAMP/PKA/p-CREB Pathway Activation.

Background: Konjac oligosaccharide (KOS), which is produced through the degradation of konjac glucomannan via enzymatic, chemical, or physical treatments, has been found to have laxative effects. The current study aimed to elucidate the mechanisms underlying the laxative effect of KOS.

Methods: KOS was administered by gavage to wild-type and 5-hydroxytryptamine 4 receptor (5-HT4R)-knockout C57BL/6 mice subjected to loperamide-induced constipation for four weeks. Following treatment, feces, blood, small intestine, colonic tissue, and intestinal contents were collected. Constipation-related parameters, gastrointestinal hormones, and Ca2+ concentrations were evaluated. Histopathological changes were examined via hematoxylin and eosin staining. Immunofluorescence staining, Western blotting, and immunohistochemical staining were performed to detect the 5-HT4R/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. Isolated smooth muscle cells (SMCs) were treated with KOS and GR113808 (a 5-HT4R antagonist), morphologically observed under an inverted microscope, and identified by α-SMA immunofluorescence staining. Cell viability was assessed via CCK-8 assays. 5-HT4R/cAMP/PKA/p-CREB pathway activity in SMCs was detected via Western blotting.

Results: KOS alleviated loperamide-induced constipation in mice. KOS activated the 5-HT4R/cAMP/PKA/p-CREB pathway in loperamide-induced constipated mice. The protective effect of KOS was significantly diminished in 5-HT4R-/- mice. KOS promoted the proliferation of SMCs by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.

Conclusion: KOS improves loperamide-induced constipation by activating the 5-HT4R/cAMP/PKA/p-CREB signaling pathway.

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来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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