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H2S通过抑制PERK/Bax-Bcl2通路来缓解败血症引起的急性损伤
Chengqing Song1, Qian Chen1, Jiao Xu1
1Department of Physiology, Hebei Medical University, 361 Zhongshan East Road, 050017, Shijiazhuang, Hebei, China.
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概括
硫化 (H2S) 通过减少炎症和内质网膜应激 (ERS) 来预防败血症引起的急性损伤 (SAKI). 外源H2S通过抑制PERK/Bax-Bcl2通路来缓解损伤,这表明H2S在SAKI中的治疗作用.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 败血症引起的急性损伤 (SAKI) 是一种具有高死亡率的危急疾病.
- 细胞内膜网膜应激 (ERS) 在SAKI的发病过程中起着重要作用.
- 硫化 (H2S) 在各种伤害模型中以其保护作用而闻名.
研究的目的:
- 在SAKI的小鼠模型中研究H2S的保护机制.
- 确定内源和外源H2S在SAKI中的作用.
- 阐明涉及H2S介导的SAKI防护中的分子通路.
主要方法:
- 在小鼠中使用腹腔内脂多糖 (LPS) 注射诱导SAKI.
- 评估了炎症标志物 (TNF-α,Bun) 的水平和脏组织病理学.
- 分析了H2S生成酶和参与ERS和亡的蛋白质 (GRP78,ATF6,PERK,Bax/Bcl2) 的表达.
- 评估了用dl-propargylglycine (PPG) 抑制CSE活性的影响.
主要成果:
- LPS注射显著增加了TNF-α和Bun水平,并导致脏损伤.
- 在SAKI小鼠中,H2S生成酶的下调,ERS和亡标志物的上调.
- H2S治疗改善了功能,减轻了损伤,并减少了ERS.
- 抑制H2S生产加剧了损伤,并激活了PERK/Bax-Bcl2通路.
结论:
- 内生H2S在SAKI的发病过程中起作用.
- 外源H2S对LPS诱导的AKI具有保护作用.
- H2S通过抑制与ERS有关的PERK/Bax-Bcl2通路来缓解SAKI.
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