分子机制 通过GPR37对性结肠炎的饮食纤维宁干预的研究
Hanhan Xie1, Ji Yang2, Tong Liu3
1The Second Affiliated Hospital of Chengdu Medical College, China Nation Nuclear Corporation 416 Hospital, Chengdu 610057, China.
Journal of agricultural and food chemistry
|June 7, 2024
概括
食中含有的植物纤维宁通过抑制铁和调节肠道微生物群,对性结肠炎 (UC) 产生保护作用. 氨酸激活ERK-NRF2-GPX4通路,为UC治疗提供新的治疗途径.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 营养科学 营养科学
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病,治疗选择有限.
- 食纤维,如素,具有抗氧化和抗炎性质,但其在UC中的作用尚未完全理解.
- 铁亡,一种受调节的细胞死亡形式,与UC病变发生有关.
研究的目的:
- 在小鼠中研究红素对硫酸 (DSS) 诱导的UC的保护作用.
- 阐明潜在的分子机制,包括铁灭调节和信号通路.
- 评估红素对肠道微生物群组成的影响,并将其有效性与5-氨基酸 (5-ASA) 进行比较.
主要方法:
- 由DSS诱导的UC小鼠模型.
- 一周的莱格宁治疗.
- 评估疾病活动指数 (DAI),组织学损伤和细胞死亡.
- 对铁病标记物的分析 (GPX4,4-HNE,转素),铁过载,谷氨 (GSH),活性氧物种 (ROS) 和甲 (MDA).
- 在肠上皮细胞 (IEC) 中评估NRF2和ERK激活.
- 对素与GPR37.7结合的研究.
- 用于肠道微生物群分析的16S rRNA测序.
主要成果:
- 在UC小鼠中,红素显著抑制了DAI,组织学损伤和细胞死亡.
- 灵宁通过增加GPX4和降低4-HNE和转移素表达,减轻铁过载,GSH耗尽,ROS和MDA生产来逆转铁变.
- 宁治疗导致NRF2的表达增加,并在IEC中激活其上游调节器ERK.
- 发现利格宁可以结合GPR37.
- 利格宁改善了DSS小鼠的肠道菌群组成,表现出与5-ASA.相似的效果.
结论:
- 利格宁通过抑制铁亡,显示出对UC的显著保护作用.
- 该机制涉及ERK-NRF2-GPX4信号轴的激活和与GPR37.7结合.
- 利格宁还通过调节肠道微生物群来改善UC.
- 这些发现突出了素作为UC治疗的潜在治疗剂.
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