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维生素D/维生素D受体通过降低C5aR调节,减轻西斯普拉丁诱导的急性损伤
Zhouyu Wen1, Can Sun1, Yan Lou2
1Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, China.
Journal of immunotoxicology
|September 5, 2023
概括
维生素D (VD) 通过抑制补充受体C5aR.保护免受西斯普拉丁诱导的急性损伤 (AKI). 这种机制减少了炎症和损伤,为化疗相关的损伤提供了新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
背景情况:
- 西斯普拉丁 (DDP) 化疗可以导致急性损伤 (AKI).
- 对DDP诱导的AKI的有效治疗方法有限.
- 补充系统,特别是C5aR,是潜在的治疗点.
研究的目的:
- 调查维生素D (VD) 对DDP诱导的AKI的治疗潜力.
- 阐明涉及C5aR和VD受体 (VDR) 的潜在分子机制.
主要方法:
- 在体内 (小鼠) 和体内 (HK-2细胞) 建立的DDP诱导的AKI.模型.
- 通过组织学,免疫组织化学,免疫光学,RT-PCR和西部斑点评估功能,损伤和C5aR表达.
- 利用 luciferase 递质基因测定和 ChIP 分析来确定通过 VDR. 的 C5aR 转录调节.
主要成果:
- 静脉疾病治疗减少了DDP诱导的病态损伤和炎症标志物 (TNFα,IL-1β,IL-18).
- 静脉疾病治疗降低了C5aR表达,但其过度表达降低了静脉疾病的保护作用.
- 已经证明VDR可以通过转录抑制C5aR表达.
结论:
- VD/VDR通过转录抑制C5aR表达来延迟DDP诱导的AKI.
- 这种抑制减少了下游的促炎性细胞因子的产生.
- 这项研究揭示了VD/VDR在急性炎中的调节机制,为DDP诱导的AKI提供了治疗见解.
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