中国药理学通报2025，Vol.41Issue(8)：1478-1484,7.DOI:10.12360/CPB202412110
PU.1抑制剂对MRL/lpr小鼠狼疮性肾炎的治疗作用
Effect of PU.1 inhibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism
摘要
Abstract
Aim To investigate the effect of PU.1 in-hibitor DB2313 on lupus nephritis in MRL/lpr mice and its mechanism.Methods Thirty female MRL/lpr mice were randomly divided into the model group,DB2313 group and TACI-Ig group,with 10 mice in each group.Another 10 female BALB/c mice were se-lected as normal control groups.Mice in the DB2313 group received intraperitoneal DB2313 injections every two days,and those in the TACI-Ig group received subcutaneous injections of TACI-Ig every two days.Mice in the control group and model group were intra-gastrically given the same amount of 0.9％NaCl injec-tion every day.Before the drug intervention and for 1 to 5 weeks after the intervention,the urine of mice was collected regularly,the urine protein content was meas-ured,and the renal damage index was evaluated.The histopathological changes of kidney were observed by HE,Masson and PAS staining.The expression levels of immune complex of C3 in kidney tissue were detec-ted by immunohistochemistry.The concentrations of u-rea nitrogen(BUN),serum creatinine(Scr),inter-leukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)in the serum samples were assayed utilizing the respective kits.The expression levels of PU.1 and FLT3 in kidney tissues were determined by immunoflu-orescence technology,and the protein expressions of PU.1,FLT3,PI3K,AKT and phosphorylated AKT(p-AKT)in kidney tissues were detected by Western blot.Results DB2313 treatment significantly allevia-ted the pathological damage of kidney in MRL/lpr mice,and reduced the deposition of C3,kidney injury index and 24-hour urine protein in renal tissue.The results of ELISA showed that DB2313 administration could significantly reduce the serum levels of BUN,Scr,IL-6 and TNF-α in MRL/lpr mice.The results of immunofluorescence and Western blot further showed that DB2313 treatment could significantly down-regu-late the protein expression of PU.1,PI3K and p-AKT,and up-regulate the protein expression of FLT3.Con-clusion DB2313 has an ameliorating effect on lupus nephritis in MRL/lpr mice,and its underlying mecha-nism may involve the inhibition of the transcription fac-tor PU.1-mediated signaling pathway.关键词
狼疮性肾炎/MRL/lpr小鼠/DB2313/PU.1/FLT3/PI3KKey words
lupus nephritis/MRL/lpr mice/DB2313/PU.1/FLT3/PI3K分类
医药卫生引用本文复制引用
徐诺,郭婷婷,李颖,王康,魏伟,严尚学..PU.1抑制剂对MRL/lpr小鼠狼疮性肾炎的治疗作用[J].中国药理学通报,2025,41(8):1478-1484,7.基金项目
安徽高校自然科学研究重大项目(No KJ2020ZD15) （No KJ2020ZD15）
安徽省转化医学研究院科研基金重点项目(No 2023zhyx-B14) （No 2023zhyx-B14）
