中国免疫学杂志2024,Vol.40Issue(7):1381-1386,6.DOI:10.3969/j.issn.1000-484X.2024.07.006
维生素D通过抑制NLRP3炎症小体的活化改善肾脏缺血再灌注损伤
Vitamin D ameliorates renal ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation
摘要
Abstract
Objective:To investigate the role and mechanism of vitamin D(VD)in renal ischemia-reperfusion(I/R group)injury.Methods:Forty-eight male C57BL/6J mice were divided into four groups:Sham operation group(Sham group),active VD analog alfacalcidol treatment group(VD group),renal ischemia-reperfusion injury group(I/R group)and alfacalcidol treated I/R group(I/R+VD group).After 24 h renal I/R injury,mice in each group were sacrificed,and peripheral blood was collected to detect the levels of blood urea nitrogen(BUN),serum creatinine(SCr)and inflammatory factors IL-1β,IL-18 and tumor necrosis factor-α(TNF-α).The renal tissues of mice in each group were collected,the apoptosis level of renal tissues was detected by TUNEL staining,and the positive expression rate of NLRP3 was detected by IHC.Western blot was used to detect the NLRP3 inflammasome associated factors NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and NF-κB p65,IκBα in renal tissues of mice in each group.Results:Com-pared with Sham group,there was no significant difference in serum BUN,SCr,IL-1β,IL-18 and TNF-α levels in VD group(P>0.05),significantly increased in I/R group and I/R+VD group(P<0.05).Compared with I/R group,BUN,SCr,IL-1β,IL-18 and TNF-α were significantly decreased in I/R+VD group(P<0.05).Compared with Sham group,the positive rate of TUNEL and NLRP3 expression in renal tissues of mice in VD group had no significant difference(P>0.05),the positive rate of TUNEL and NLRP3 expres-sion in renal tissues of mice in I/R group and I/R+VD group were significantly increased(P<0.01),while the positive rate of TUNEL and NLRP3 expression in I/R+VD group were significantly decreased(P<0.05).Western blot results showed that compared with Sham group,there was no significant difference in protein expression levels of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β,NF-κB P65,IκBα in VD group(P>0.05).The protein expression of IκBα in I/R group and I/R+VD group was significantly decreased(P<0.05),while the other protein expression levels were significantly increased(P<0.05).Compared with the I/R group,the expression levels of NLRP3,GSDMD-N,cleaved Caspase-1,IL-1β and NF-κB p65 were significantly decreased in the I/R+VD group(P<0.05),while the expression level of IκBα was significantly decreased(P<0.05).Conclusion:VD plays a protective role in I/R injury by inhibiting NF-κB mediated activation of NLRP3 inflammasome.关键词
维生素D/NLRP3炎症小体/肾脏缺血再灌注损伤/NF-κB信号通路/炎症反应Key words
Vitamin D/NLRP3 inflammasome/Renal ischemia-reperfusion injury/NF-κB signaling pathway/Inflammatory response分类
医药卫生引用本文复制引用
王平,李辉,谢枫,苑晓姣..维生素D通过抑制NLRP3炎症小体的活化改善肾脏缺血再灌注损伤[J].中国免疫学杂志,2024,40(7):1381-1386,6.基金项目
兵团科技攻关项目(2018AB024). (2018AB024)