莪术醇对肝星状细胞铁死亡和上皮间质转换作用的研究
Effects of curcumol on iron death and epithelial-mesenchymal transition in hepatic stellate cells
汪磊 1黄金彪 2黄艳青 2王泽宇 2王佳慧 2郑洋 2罗伟生 3赵铁建4
作者信息
- 1. 广西中医药大学研究生学院,广西壮族自治区南宁 530222;广西中医药大学赛恩斯新医药学院,广西壮族自治区南宁 530222
- 2. 广西中医药大学赛恩斯新医药学院,广西壮族自治区南宁 530222
- 3. 广西中医药大学研究生学院,广西壮族自治区南宁 530222
- 4. 广西中医药大学赛恩斯新医药学院,广西壮族自治区南宁 530222;广西中医药大学壮瑶药重点实验室,广西壮族自治区南宁 530222
- 折叠
摘要
目的 探究莪术醇对肝星状细胞铁死亡和上皮间质转换(EMT)的影响,及其抗肝纤维化的分子机制.方法 用体外正常培养的肝星状细胞构建肝星状细胞活化模型,并分为空白组和低、中、高剂量实验组.空白组给予DMEM完全培养液正常培养;低、中、高剂量实验组分别给予含12.5、25.0、50.0 mg·L-1莪术醇的DMEM完全培养液干预48 h.用CCK-8法观察莪术醇对肝星状细胞增殖的影响,用蛋白质印迹法检测谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)的表达水平,用免疫荧光法检测E-钙黏蛋白(E-cadherin)和N-cadherin的表达情况.结果 中、高剂量实验组和空白组的细胞增殖率分别为(68.97±5.61)％、(61.91±4.40)％和(118.07±10.01)％,GPX4 相对表达水平分别为0.37±0.04、0.28±0.03和0.58±0.05,SLC7A11相对表达水平分别为 0.38±0.04、0.28±0.03 和 0.60±0.05,E-cadherin 分别为6.76±1.09、9.57±1.73和 2.05±0.72,N-cadherin 分别为 5.66±0.66、3.44±0.78 和10.37±0.66.空白组的上述指标和中、高剂量实验组比较,在统计学上差异均有统计学意义(P＜0.05,P＜0.01)c结论 莪术醇促进肝星状细胞铁死亡,从而抑制肝星状细胞EMT,这可能是其防治肝纤维化分子机制.
Abstract
Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)％,(61.91±4.40)％and(118.07±10.01)％;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.
关键词
莪术醇/肝星状细胞/铁死亡/上皮间质转换/肝纤维化Key words
curcumol/hepatic stellate cell/ferroptosis/epithelial-mesenchymal transition/liver fibrosis引用本文复制引用
基金项目
国家自然科学基金资助项目(81960751)
国家自然科学基金资助项目(82204755)
广西壮瑶药重点实验室基金资助项目(GXZYYKF2023-05)
广西中医药大学青年基金资助项目(2022MS024)
广西中医药大学青年基金资助项目(2022QN008)
广西中医药大学赛恩斯新医药学院科研基金资助项目(2022MS002)
广西中医药大学赛恩斯新医药学院科研基金资助项目(2022MS008)
广西中医药大学赛恩斯新医药学院科研基金资助项目(2022QJ001)
广西中医药大学赛恩斯新医药学院国家级大学生创新创业训练基金资助项目(202313643008)
出版年
2024
国家科技期刊平台
NSTL
万方数据