中国中西医结合杂志2025，Vol.45Issue(8)：944-951,8.DOI:10.7661/j.cjim.20250618.083
升清降浊方下调TLR4/NF-κB/NLRP3通路减轻糖尿病肾病小鼠肾损伤
Shengqing Jiangzhuo Formula Alleviates Kidney Injury in Mice with Diabetic Kidney Disease via Down-regulating TLR4/NF-κB/NLRP3 Pathway
摘要
Abstract
Objective To explore the effect of Shengqing Jiangzhuo Formula(SJF)on Toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)/nucleotide oligomerization domain-(NOD-)like receptor family pyrin domain containing 3(NLRP3)pathway,and its mechanism of intervention in diabetic kidney disease(DKD).Methods Thirty db/db mice were randomly divided into the model,TLR4 inhibitor(TAK-242,3 mg/kg),low-,medium-,and high-dose SJF groups that received SJF(1.021,2.041,4.082 g·kg-1·d-1 respectively),6 mice in each group.An additional 6 db/m mice were selected as the normal control group.Each group was administered with corresponding dose of drugs or distilled water via gavage for 8 weeks.The 24-hour urine protein(UTP),as well as serum levels of urea nitrogen,creatinine(SCr),interleukin-1 β(IL-1 β),and interleukin-18(IL-18)were assessed in each group following the drug administration.Haematoxylin and Eosin staining was used to observe pathological changes in the kidneys of the mice,and TUNEL staining was used to detect DNA damage in renal tissue cells.Immunohistochemistry was used to assess the expression levels of the IL-1β,IL-18,and transforming grouth factor(TGF)-β1 proteins in the kidneys of the mice,while the expression levels of key TLR4/NF-κB/NLRP3 signaling pathway proteins were determined via Western Blot.Results Compared to the normal group,the glomerular capillary basement membranes in the model group tended to be diffused and thickened,more inflammatory cells had infiltrated the renal interstitial space,the renal histopathological scores were higher(P＜0.01),DNA damage in the renal tissue cells was significantly higher(P＜0.01),and the UTP levels and the serum SCr,IL-1 β,and IL-18 levels increased(P＜0.01),as were the expression levels of IL-1β,IL-18,TGF-β1,TLR4,NF-κB p-p65,Myeloid differentiation primary response protein 88(MyD88),NLRP3,cysteinyl aspartate specific proteinase(Caspase)-1,and Gasdermin D(GSDMD)-N in the renal tissues(P＜0.01).Compared to the model group,the medium-and high-dose SJF groups as well as the TLR4 inhibitor group showed significantly less diffuse thickening of the glomerular basement membrane of the kidney nephron,corresponding reductions in interstitial inflammatory cell infiltration,and lower renal histopathological scores(P＜0.05).The levels of DNA damage in the renal tissue cells of the TLR4 inhibitor group,as well as the low-,medium-,and high-dose SJF groups were all significantly lower(P＜0.01).Serum UTP,as well as IL-1 β and IL-18 levels decreased in these groups(P＜0.01),and as were the expression levels of IL-1 β,IL-18,TGF-β1,TLR4,NF-κBp-p65,MyD88,NLRP3,Caspase-1 and GSDMD-N in the renal tissues(P＜0.01).Conclusions The administration of SJF may reduce inflammatory reactions and pyroptosis in renal tissues,by down-regulating the TLR4/NF-κB/NLRP3 signalling pathway and alleviating renal injury in DKD mice.关键词
糖尿病肾病/细胞焦亡/TLR4/NF-κB/NLRP3通路/炎症反应/升清降浊方/中药复方Key words
diabetic kidney disease/pyroptosis/TLR4/NF-κB/NLRP3 pathway/inflammatory response/Shengqing Jiangzhuo Formula/Chinese herbal compound引用本文复制引用
檀淼,杨冰,唐淼,温小多,苏明明,檀金川,宋瑞婧..升清降浊方下调TLR4/NF-κB/NLRP3通路减轻糖尿病肾病小鼠肾损伤[J].中国中西医结合杂志,2025,45(8):944-951,8.基金项目
河北省卫健委青年科技课题(No.20241868) （No.20241868）
