中国药房2025，Vol.36Issue(18)：2232-2237,6.DOI:10.6039/j.issn.1001-0408.2025.18.03
骨化三醇通过VDR/Ca2+/细胞焦亡信号通路逆转脓毒症免疫抑制
Calcitriol reverses sepsis-induced immunosuppression via VDR/Ca2+/pyroptosis signaling pathway
摘要
Abstract
OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism.METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture(CLP).The 7-day survival rate,serum levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β were determined in sham operation group,CLP group and calcitriol group(1 μg/kg);the morphological changes of lung tissue in mice were observed.Lipopolysaccharide(LPS)tolerance macrophage models(representing sepsis-induced immunosuppression)were established using mice macrophage cell line RAW264.7 cells.The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β,nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3),IL-18 and caspase-1 were assessed in culture medium group,LPS group,LPS tolerance group,and calcitriol(5 μmol/L)group.The following parameters were measured:propidium iodide(PI)-positive cell ratio,caspase-1 activity,lactate dehydrogenase(LDH)release,and Ca2+levels.RESULTS Compared with CLP group,7-day survival rate and serum levels of TNF-α,IL-6 and IL-1β were increased significantly in calcitriol group(P＜0.05).Additionally,pulmonary tissue damage was markedly attenuated in calcitriol group.Compared with LPS tolerance group,the levels of TNF-α and IL-6 in cell supernatants,mRNA expressions of IL-1β,NLRP3,IL-18 and caspase-1,PI-positive cell ratio,caspase-1 activity,LDH release,and Ca2+levels were all increased significantly in calcitriol group(P＜0.05).CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression,and the mechanism of action may be achieved by the binding of calcitriol to vitamin D receptor,which promotes the release of Ca2+from the endoplasmic reticulum,thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.关键词
骨化三醇/脓毒症/免疫抑制/细胞焦亡/Ca2+Key words
calcitriol/sepsis/immunosuppression/pyroptosis/Ca2+分类
医药卫生引用本文复制引用
尚圣兰,邹硕,魏宇琪,余梦辰,周帆,赵燕,余爱荣..骨化三醇通过VDR/Ca2+/细胞焦亡信号通路逆转脓毒症免疫抑制[J].中国药房,2025,36(18):2232-2237,6.基金项目
国家自然科学基金项目(No.82304576) （No.82304576）
中国博士后科学基金项目(No.2022M713859) （No.2022M713859）
湖北省自然科学基金项目(No.2022CFB879) （No.2022CFB879）
武汉市知识创新专项(No.2022020801020521) （No.2022020801020521）
