中药药理与临床2025，Vol.41Issue(2)：33-39,7.
姜黄素通过影响线粒体跨膜电位和TLR4/NF-κB信号通路减轻LPS诱导急性肺损伤
Curcumin Alleviates LPS-Induced Acute Lung Injury by Regulating Mitochondrial Transmembrane Potential and TLR4/NF-κB Signaling Pathway
摘要
Abstract
Objective:To investigate whether curcumin(Cur)inhibits lipopolysaccharide(LPS)-induced acute lung injury(ALI)by regulating the mitochondrial transmembrane potential(MMP)and Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB signaling pathway.Methods:RAW264.7 cells were classified into blank control,model,Cur(5,10,and 20 μmol/L),and dexamethasone(Dex,10 μmol/L)groups.The cells were simulated by 10 ng/mL LPS.The viability,apoptosis,and MMP of RAW264.7 cells were measured by the cell counting kit-8(CCK-8)assay,Annexin V-FITC/PI staining,and JC-1 staining,respectively.The protein levels of TLR4,NF-κB,B cell lymphoma-2(BCL-2),and Bcl-2-associated protein X(BAX)were determined by Western blotting.The levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β,and IL-10 in the supernatant were measured by enzyme-linked immunosorbent assay(ELISA).In the animal experiment,72 Kunming mice were assigned into sham,model,Cur(50,100,and 200 mg/kg),and Dex(10 mg/kg)groups.The mouse model of ALI was constructed by intratracheal instillation of 50 mg/mL LPS.Among them,36 mice were used to measure the lung wet/dry ratio.The patho-logical changes in the lung tissue were observed by hematoxylin-eosin staining,and the protein levels of TLR4 and NF-κB in the lung tissue were determined by Western blotting.The levels of TNF-α,IL-6,IL-1β,and IL-10 in the bronchoalveolar lavage fluid of the remaining 36 mice were measured by ELISA.Results:Compared with the blank control group,the modeling decreased the survival rate and increased the apoptosis rate of RAW264.7 cells(P<0.01),increased the BAX/BCL-2 ratio by down-regulating the expression of BCL-2 and up-regula-ting the expression of BAX(P<0.01),decreased MMP(P<0.01),up-regulated the protein levels of TLR4/NF-κB(P<0.01),elevated the levels of TNF-α,IL-6,and IL-1β(P<0.01),while lowered the level of IL-10(P<0.01)in RAW264.7 cells.Compared with the model group,Cur increased the survival rate(P<0.05)and decreased the apoptosis rate(P<0.01)of RAW264.7 cells,reduced the BAX/BCL-2 ratio(P<0.05),increased the MMP(P<0.05),down-regulated the protein levels of TLR4/NF-κB(P<0.05),lowered the levels of TNF-α,IL-6,and IL-1β(P<0.01),and elevated the IL-10 level(P<0.05)in RAW264.7 cells.Compared with the sham group,the modeling with LPS aggravated the lung injury and increased the lung wet/dry ratio(P<0.01),up-regulated the protein levels of TLR4/NF-κB in the lung tissue(P<0.01),elevated the levels of TNF-α,IL-6,and IL-1β(P<0.01),and lowered the level of IL-10 in the lung tissue(P<0.01).Compared with the model group,Cur of all doses alleviated the LPS-induced pathological injury and lung wet/dry ratio(P<0.01),down-regu-lated the expression of TLR4/NF-κB in the lung tissue(P<0.01),lowered the levels of TNF-α,IL-6,and IL-1β(P<0.01),and elevated the level of IL-10(P<0.05)in the lung tissue.Conclusion:Cur may alleviate LPS-induced ALI by increasing mitochondrial transmembrane po-tential,inhibiting TLR4/NF-κB signaling pathway,and ultimately inhibiting apoptosis.关键词
姜黄素/急性肺损伤/线粒体跨膜电位/Toll样受体 4/核因子-κB/凋亡Key words
Curcumin/Acute lung injury/Mitochondrial membrane potential/Toll-like receptor 4(TLR4)/Nuclear factor(NF)-κB/Apoptosis引用本文复制引用
赵浩,黄江,陈圣东,陈修瑞,张婉婷,章卓..姜黄素通过影响线粒体跨膜电位和TLR4/NF-κB信号通路减轻LPS诱导急性肺损伤[J].中药药理与临床,2025,41(2):33-39,7.基金项目
2023年度四川省中医药管理局中医药科研专项课题面上项目(编号:2023577) （编号:2023577）
泸州市科技局项目(编号:2018LZXNYD-ZK46). （编号:2018LZXNYD-ZK46）
