中药药理与临床2025，Vol.41Issue(7)：45-51,7.
冬虫夏草蛋白调控p38/JNK MAPK信号通路缓解狼疮性肾炎
Dongchongxiacao(冬虫夏草)Protein Alleviates Lupus Nephritis by Regulating p38/JNK MAPK Signaling Pathway
摘要
Abstract
Objective:To investigate the role and mechanism of Dongchongxiacao(冬虫夏草)protein in alleviating lupus nephritis(LN)by cell and animal experiments based on the immune infiltration characteristics.Methods:A data set of the kidney tissue in LN patients was obtained from the Gene Expression Omnibus(GEO).Immune cell infiltration in the kidneys was analyzed by R,Import,and CIBERSORT.The im-mune infiltration characteristics in the kidneys of LN patients were assessed by the random forest method.The total protein of Dongchongxia-cao was extracted and its composition was identified by LC-MS/MS.M1-type macrophage model was established,and real-time fluorescence quantitative PCR and flow cytometry were employed to evaluate the effect of Dongchongxiacao protein on M1-type macrophage polarization.An LN model was established in MRL/lpr mice,and the effects of Dongchongxiacao total protein on M1-type macrophage polarization were exam-ined by ELISA,hematoxylin-eosin(HE)staining,periodic acid-Schiff(PAS)staining,flow cytometry,and immunofluorescence.Further-more,the protein levels of p38,phosphorylated p38(p-p38),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),c-Jun N-terminal kinase(JNK),and phosphorylated JNK(p-JNK)in the M1-type macrophages treated with Dongchongxiacao total protein were determined by Western blot.Results:Immune infiltration analysis revealed M1-type macrophages in the kidneys of LN patients increased,sug-gesting that targeting renal M1-type macrophage infiltration might be a promising treatment approach for LN.A total of 422 non-redundant proteins were identified in Dongchongxiacao.In the cell experiment,compared with the model group,Dongchongxiacao protein(100,200,and 400 μg/mL)down-regulated the mRNA levels of inducible nitric oxide synthase(iNOS)and interleukin(Il)-1β in macrophages(P<0.01)and inhibited the polarization of M1-type macrophages(F4/80+CD86+)(P<0.05).In the animal experiment,compared with the model group,Dongchongxiacao protein led to a reduction of urinary protein content(P<0.01),an increase of urinary creatinine level(P<0.01),and decreases of levels of dsDNA antibody and anti-nuclear antibody(ANA)in the serum(P<0.05).HE and PAS staining results indicated that Dongchongxiacao protein attenuated the renal tissue damage in mice after treatment.The results of real-time PCR,immunofluorescence,and flow cytometry suggested that Dongchongxiacao protein reduced the infiltration of M1-type macrophages in the kidneys of the mouse model of LN(P<0.05).Western blot results suggested that Dongchongxiacao protein down-regulated the expressions of p-p38 and p-JNK(P<0.05).Conclusion:Dongchongxiacao protein may alleviate LN by inhibiting M1-type macrophage activation via the p38/JNK MAPK signa-ling pathway.关键词
冬虫夏草/蛋白/狼疮性肾炎/巨噬细胞/极化/c-JUN氨基末端激酶/细胞外信号调节激酶/p38蛋白激酶Key words
Dongchongxiacao(冬虫夏草)/Protein/Lupus nephritis/Macrophage/Polarization引用本文复制引用
周小仝,何丽英,廖郑悦,杨兴茂,李勇,白静,牛舒琪,刘思静,国锦琳..冬虫夏草蛋白调控p38/JNK MAPK信号通路缓解狼疮性肾炎[J].中药药理与临床,2025,41(7):45-51,7.基金项目
国家自然科学基金(编号:81872959、81373920) （编号:81872959、81373920）
四川省科技厅自然科学基金(编号:2023NSFSC1757). （编号:2023NSFSC1757）
