中国药理学通报2024，Vol.40Issue(9)：1701-1708,8.DOI:10.12360/CPB202403070
姜黄素调控TLR4/NF-κB和NRF2/HO-1信号通路改善草酸钙晶体诱导的小鼠肾损伤
Curcumin attenuates calcium oxalate crystal-induced renal injury via regulation of TLR4/NF-κB and NRF2/HO-1 pathways in mouse model
摘要
Abstract
Aim To investigate the protective effects of curcumin(CUR)on crystal-induced renal injury and its underlying mechanism in the mouse model of neph-rolithiasis.Methods The mouse model of stone for-mation was established via successive intraperitoneal injection of glyoxylate.Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate(COM)was used as an in vitro model.The protective role of CUR on nephrolithiasis was tested by determina-tion of tubular injury,crystal deposition and adhesion,levels of inflammatory cytokines.In vitro,the effects of CUR on the cell viability and inflammatory factors of HK-2 cells were measured.The proteins in the Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)and nuclear factor erythroid 2-related factor 2(NRF2)/hemeoxygenase-1(HO-1)signaling path-ways were measured by Western blot for confirming the relationship between CUR and these pathways.Final-ly,NRF2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on COM-induced HK-2 cells ex-posed to CUR for the conduction of gain-of-function and loss-of-function assays.Results CUR improves the damage in the mouse model of kidney stone forma-tion,inhibits inflammation and antioxidative effects;promotes the viability of HK-2 cells induced by COM,and inhibits the expression of inflammatory factors.CUR suppresses the expression of proteins in the TLR4/NF-κB pathway,promotes the transfer of NRF2 from the cytoplasm to the nucleus,and enhances the ex-pression of HO-1.ML385 and CCL-34 respectively counteract the anti-inflammatory effects of CUR on COM-induced HK-2 cells.Conclusions Taken togeth-er,our study demonstrates the protective effect of CUR on the deposition of kidney stone and consequent tubu-lar injury.CUR through regulation of the TLR4/NF-κB and NRF2/HO-1 pathways improves renal injury.关键词
姜黄素/肾结石/肾小管上皮细胞/Toll样受体4/NRF2/炎症Key words
curcumin/calculus of kidney/renal tu-bular epithelial cells/TLR4/NRF2/inflammation分类
医药卫生引用本文复制引用
何彦丰,赖文斌,陈文炜,刘昌毅,卢凯鑫,张华,江涛,高锐..姜黄素调控TLR4/NF-κB和NRF2/HO-1信号通路改善草酸钙晶体诱导的小鼠肾损伤[J].中国药理学通报,2024,40(9):1701-1708,8.基金项目
福建省教育厅中青年教师教育科研项目(No JAT200127) （No JAT200127）
福建医科大学启航基金项目(No 2020QH1021) （No 2020QH1021）
