兰索普拉通过p38 MAPK/ARE/Nrf2通路保护肝细胞免受西斯普拉丁诱导的氧化应激
Naoko Yamagishi1, Yuta Yamamoto1, Toshio Nishi1
1Department of Anatomy and Cell Biology, Graduate School of Medicine, Wakayama Medical University, Wakayama, Japan.
PloS one
|June 29, 2023
概括
兰索普拉通过激活Nrf2通路和p38 MAPK信号来保护肝细胞免受损伤. 这种抗氧化作用增强了细胞存活率,可以抵御西斯胺诱导的毒性,这表明有治疗肝氧化损伤的潜力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子药理学分子药理学
- 细胞生物学 细胞生物学
背景情况:
- 像兰索普拉这样的质子抑制剂通过Nrf2通路表现出抗氧化特性.
- 兰索普拉在药物诱导性肝炎的动物模型中显示出肝保护作用.
- 兰索普拉的细胞保护作用背后的精确分子机制需要进一步阐明.
研究的目的:
- 研究兰索普拉在肝细胞中诱导的细胞保护的分子机制.
- 确定Nrf2通路和特定信号级联在兰索普拉的保护作用中的作用.
- 为了在体外评估兰索普拉对西斯普拉丁诱导的细胞毒性的疗效.
主要方法:
- 使用培养的老鼠肝细胞进行体外研究 (RL34).
- 对Nrf2表达,下游基因诱导 (HO1,NQO1,GSTA2) 和Nrf2活动的分析.
- 在西斯普拉丁诱导的细胞毒性模型中评估细胞活力.
- 使用特定抑制剂和siRNA的信号通路 (MAPK家族) 和蛋白质半衰期的研究.
主要成果:
- 兰索普拉醇诱导了Nrf2的交换活化和抗氧化基因的表达 (HO1,NQO1,GSTA2).
- 兰索普拉治疗延长了Nrf2蛋白的半衰期.
- 兰索普拉显著增加了细胞活力,抵御了西斯普拉丁诱导的细胞毒性.
- 细胞保护作用依赖于Nrf2和p38 MAPK通路,但不是ERK或JNK.
结论:
- 兰索普拉对肝细胞产生细胞保护作用,对抗西斯普拉丁诱导的损伤.
- 该机制涉及Nrf2通路和p38 MAPK信号的激活.
- 这些发现表明兰索普拉在预防和治疗肝氧化损伤方面的潜在治疗应用.
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