中国中药杂志2026，Vol.51Issue(7)：1891-1902,12.DOI:10.19540/j.cnki.cjcmm.20260108.309
基于上皮-间充质转化探讨盐炙杜仲治疗肾纤维化增效的机制研究
Study on mechanism of salt-stir fried Eucommiae Cortex to enhance therapeutic efficacy on renal fibrosis through epithelial-mesenchymal transition
摘要
Abstract
This study aims to systematically compare the differences in the effects of Eucommiae Cortex(EC)and salt-stir fried Eucommiae Cortex(SEC)on improving adenine-induced renal fibrosis in rats and explore the molecular mechanism by which SEC enhances the therapeutic effect on renal fibrosis based on epithelial-mesenchymal transition(EMT).Rats were randomly divided into a blank control group,model group,positive drug group,and groups with low,medium,and high-dose EC and SEC.Western blot and immunofluorescence techniques were utilized to detect the expression of fibrosis marker proteins such as α-smooth actin(α-SMA),collagen Ⅰ,fibronectin,and vimentin in renal tissue.Real-time fluorescent quantitative reverse transcription polymerase chain reaction(PCR)was used to detect the transcriptional expression levels of key EMT transcription factors snail family transcriptional repressor 1(Snai1),twist family BHLH transcription factor 1(Twist1),zinc finger E-box binding homeobox 1(ZEB1),inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in renal tissue.In in vitro experiments,a fibrosis model was established by using transforming growth factor-β(TGF-β)to stimulate renal tubular epithelial NRK-52E cells,thereby evaluating the inhibitory effects of EC and SEC on the protein expression of fibrosis markers and the EMT process.The underlying molecular mechanism was further explored by combining network pharmacology and western blot.Both EC and SEC significantly reduced the protein expression levels of fibrosis markers including fibronectin,collagen Ⅰ,vimentin,and α-SMA and obviously inhibited the transcriptional expression of key EMT transcription factors including Snai1,Twist1,and ZEB1 and inflammatory factors including TNF-α,IL-1β,and IL-6 in rats with adenine-induced renal fibrosis and in NRK-52E cells stimulated by TGF-β.The inhibitory effects of SEC were stronger than those of EC.Network pharmacology analysis revealed that the chemical components of SEC with significant change exerted the effect by focusing on the mitogen-activated protein kinase(MAPK)signaling pathway.Further experiments confirmed that both of EC and SEC significantly inhibited phosphorylation of p38 mitogen-activated protein kinase(p38)induced by adenine and TGF-β and elevated expression of its upstream apoptosis signal-regulating kinase 1(ASK1),with SEC exhibiting a more pronounced inhibitory effect.Furthermore,the ASK1 inhibitor Selonsertib significantly downregulated levels of EMT and p38 phosphorylation in NRK-52E cells stimulated by TGF-β.Therefore,SEC can enhance the therapeutic effect on renal fibrosis by inhibiting the EMT process,and its specific mechanism is related to the inhibition of the ASK1/p38 signaling pathway.关键词
杜仲/盐炙/肾纤维化/上皮-间充质转化/p38/ASK1Key words
Eucommiae Cortex/salt-stir fried/renal fibrosis/epithelial-mesenchymal transition/p38/ASK1引用本文复制引用
鲍旖旎,朱清如,周莉,余文凯,李慧婷,张卫浩,曹岗..基于上皮-间充质转化探讨盐炙杜仲治疗肾纤维化增效的机制研究[J].中国中药杂志,2026,51(7):1891-1902,12.基金项目
国家自然科学基金青年科学基金项目(82204625) （82204625）
国家重点研发计划项目(2024YFC3507002) （2024YFC3507002）
浙江省自然科学基金项目(LQ23H280013) （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(2025JKZKTS26) （2025JKZKTS26）
