中国中药杂志2025，Vol.50Issue(5)：1195-1208,14.DOI:10.19540/j.cnki.cjcmm.20241123.301
盐炙车前子调控肾小管上皮-间充质转化改善肾纤维化的机制研究
Saltwater stir-fried Plantaginis Semen alleviates renal fibrosis by regulating epithelial-mesenchymal transition in renal tubular cells
摘要
Abstract
This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS)on renal fibrosis in rats and decipher the underlying mechanism.Thirty-six Sprague-Dawley rats were randomly assigned into control,model,losartan potassium,and low-,medium-,and high-dose(15,30,and 60 g·kg-1,respectively)SPS groups.Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO)to induce renal fibrosis,and the modeling and gavage lasted for 14 days.After 14 consecutive days of treatment,the levels of serum creatinine(Scr)and blood urea nitrogen(BUN)in rats of each group were determined by an automatic biochemical analyzer.Hematoxylin-eosin(HE)and Masson staining were used to evaluate pathological changes in the renal tissue.Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN),collagen Ⅰ,vimentin,and α-smooth muscle actin(α-SMA)in the renal tissue.The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1),snail family transcriptional repressor 1(SNAI1),and zinc finger E-box binding homeobox 1(ZEB1),as well as inflammatory cytokines such as interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α),were determined by RT-qPCR.Human renal proximal tubular epithelial(HK2)cells exposed to transforming growth factor-β(TGF-β)for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT.Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis.The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats.Moreover,SPS notably down-regulated the protein levels of FN,collagen Ⅰ,vimentin,and α-SMA as well as the mRNA levels of SNAI1,ZEB1,TWIST1,IL-1β,IL-6,and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells.In addition,compared with Plantaginis Semen without stir-frying with saltwater,SPS showed increased content of specific compounds,which were mainly enriched in the mitogen-activated protein kinase(MAPK)signaling pathway.SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK)and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells.In conclusion,SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.关键词
车前子/盐炙/肾纤维化/上皮-间充质转化(EMT)/MAPK信号通路Key words
Plantaginis Semen/stir-frying with saltwater/renal fibrosis/epithelial-mesenchymal transition(EMT)/MAPK signa-ling pathway引用本文复制引用
沈鑫蕾,朱清如,余文凯,周莉,单琪媛,张易航,鲍旖旎,曹岗..盐炙车前子调控肾小管上皮-间充质转化改善肾纤维化的机制研究[J].中国中药杂志,2025,50(5):1195-1208,14.基金项目
国家自然科学基金青年科学基金项目(82204625) （82204625）
浙江省自然科学基金项目(LZ22H280001,LQ23H280013) （LZ22H280001,LQ23H280013）
浙江省中医药科技计划项目(2023ZR009) （2023ZR009）
浙江中医药大学校级科研项目(2021RCZXZK14) （2021RCZXZK14）
浙江中医药大学研究生科学研究基金项目(2023YKJ10) （2023YKJ10）
浙江省大学生科技创新活动计划(新苗人才计划)项目(2024R410A034) （新苗人才计划）
