安徽医科大学学报2024，Vol.59Issue(2)：275-281,7.DOI:10.19405/j.cnki.issn1000-1492.2024.02.015
脂氧素A4抑制TLR4/MyD88/NF-κB通路减缓脓毒症性急性肾损伤
LipoxinA4 protects sepsis-induced acute kidney injury via the TLR4/MyD88/NF-κB pathway
摘要
Abstract
Objective To study the protective effect of lipoxin A4(LXA4)against sepsis-induced acute kidney in-jury(SAKI)in rats and its effect on the expression of toll-like receptor 4(TLR4),myeloid differentiation factor88(MyD88),nuclear factor kappa B(NF-κB)in the kidney.Methods Forty male specific pathogen-free C57BL/6J mice were randomly divided into SAKI group,SAKI+LXA4 group,sham procedure group,sham procedure+LXA4 group.The mice in SAKI group and SAKI+LXA4 group were given cecum ligation and puncture(CLP)to establish SAKI animal models.The mice in SAKI+LXA4 group and sham procedure+LXA4 group were given LXA4(40 ng/kg)with intraperitoneal injection 30 mins after CLP.All mice were sacrificed at the 24th hour after CLP to collect serum,urine and kidney tissues.The enzyme linked immunosorbent assay(ELISA)was used to test the serum creat-inine(Scr),blood urea nitrogen(Bun),interleukin-1 β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM-1)levels of mice.The pathologi-cal changes were examined through hematoxylin-eosin(HE)staining and Periodic Acid-Schiff(PAS)staining.And the mRNA levels of TLR4,MyD88,NF-κB p65 were detected through real-time PCR(RT-PCR);the expression lev-els of TLR4,MyD88,NF-κB p65,phospho-NF-KB p65(p-NF-KB p65)were detected through immunohistochemistry(IHC)and Western blot assay.Results ELISA showed that the values of Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 in SAKI group were higher than those in SAKI+LXA4 group(P＜0.05),and there were no significant differences in Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 between sham procedure group and sham procedure+LXA4 group.HE and PAS staining showed that SAKI group had severer pathological changes than SAKI+LXA4 group in the kidney structure(P＜0.05),while pathological structures of the kidney were normal in sham proce-dure group and sham procedure+LXA4 group.RT-PCR showed that the mRNA levels of TLR4,MyD88,N F-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the mRNA levels of TLR4,MyD88,NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05);The results of IHC,Western blot assay were as follows:The expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05).Conclusion TLR4/MyD88/NF-KB pathway plays an important role in the occurrence and development of SAKI,and LXA4 may reduce SAKI by inhibiting TLR4/MyD88/NF-κB sig-naling pathway.关键词
脂氧素A4/Toll样受体4/髓样分化因子88/核转录因子kappa B/脓毒症/急性肾损伤Key words
lipoxinA4/toll-like receptor 4/myeloid differentiation factor88/nuclear factor kappa B/sepsis/a-cute kidney injury分类
医药卫生引用本文复制引用
龚书豪,曹春水,王缨,梅松波..脂氧素A4抑制TLR4/MyD88/NF-κB通路减缓脓毒症性急性肾损伤[J].安徽医科大学学报,2024,59(2):275-281,7.基金项目
江西省教育厅科学技术研究项目(编号:GJJ2200203) （编号:GJJ2200203）
