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1.河南省中西医结合医院中药 研究所,郑州 450004
2.郑州大学药学院,郑州 450001
3.河南中西医结合医院检验科,郑州 450004
4.郑州大学第二附属医院肾病科,郑州 450014
5.河南省中西医结合医院肺病科,郑州 450004
助理研究员,硕士。研究方向:中药药理及药效物质基础。E-mail:343499957@qq.com
主任医师,硕士。研究方向:呼吸与消化系统疾病的中医治疗。E-mail:Zhang120@126.com
收稿日期:2024-06-19,
修回日期:2024-11-08,
录用日期:2024-11-11,
纸质出版日期:2025-01-15
移动端阅览
张雪侠,周敏,周红艳,等.柿叶提取物对H2O2诱导IEC-6细胞铁死亡的影响及机制研究[J].中国药房,2025,36(01):64-70.
ZHANG Xuexia,ZHOU Min,ZHOU Hongyan,et al.Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2[J].ZHONGGUO YAOFANG,2025,36(01):64-70.
张雪侠,周敏,周红艳,等.柿叶提取物对H2O2诱导IEC-6细胞铁死亡的影响及机制研究[J].中国药房,2025,36(01):64-70. DOI: 10.6039/j.issn.1001-0408.2025.01.11.
ZHANG Xuexia,ZHOU Min,ZHOU Hongyan,et al.Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2[J].ZHONGGUO YAOFANG,2025,36(01):64-70. DOI: 10.6039/j.issn.1001-0408.2025.01.11.
目的
2
探讨柿叶(PL)提取物对过氧化氢(H
2
O
2
)诱导IEC-6细胞铁死亡的影响及潜在机制。
方法
2
以IEC-6细胞为对象,考察铁死亡抑制剂ferrostatin-1对H
2
O
2
诱导IEC-6细胞活力的影响;将IEC-6细胞分为对照组、H
2
O
2
组、H
2
O
2
+PL 25 μg/mL组、H
2
O
2
+PL 50 μg/mL组,检测其氧化应激指标[丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和活性氧(ROS)水平
]
、线粒体膜电位(MMP)以及核转录因子红系2相关因子2(Nrf2)、血红素氧合酶1(HO-1)、还原型烟酰胺腺嘌呤二核苷酸磷酸/醌氧化还原酶1(NQO-1)、胱氨酸/谷氨酸反向转运体(xCT)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链(FTH)mRNA及蛋白的表达情况。
结果
2
铁死亡抑制剂ferrostatin-1可显著升高H
2
O
2
诱导细胞的存活率(
P
<0.01)。与对照组比较,H
2
O
2
组细胞MDA含量和ROS水平,Nrf2、NQO-
1 mRNA及Nrf2、HO-1蛋白的表达均显著升高或上调;SOD活性和MMP,xCT、GPX4、FTH mRNA及GPX4、FTH蛋白的表达均显著降低或下调(
P
<0.01或
P
<0.05)。与H
2
O
2
组比较,H
2
O
2
+PL 25、50 μg/mL组细胞的氧化应激指标均有不同程度回调,MMP均显著升高,Nrf2、HO-1、NQO-1,xCT、GPX4、FTH mRNA及蛋白的表达均有不同程度上调,部分指标组间比较差异有统计学意义(
P
<0.01或
P
<0.05)。
结论
2
PL提取物能减轻H
2
O
2
所导致的细胞线粒体膜损伤、ROS异常堆积,上述作用可能与激活Nrf2/HO-1信号通路从而抑制铁死亡有关。
OBJECTIVE
2
To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis induced by H
2
O
2
in IEC-6 cells.
METHODS
2
Using IEC-6 cells as object, the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H
2
O
2
were investigated; IEC-6 cells were divided into control group, H
2
O
2
group, H
2
O
2
+PL 25 μg/mL group and H
2
O
2
+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and levels of reactive oxygen species (ROS)
]
, mitochondrial membrane potential (MMP) as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH/quinone oxidoreductase-1 (NQO-1), cystine/glutamate anti-porter (xCT), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) were detected.
RESULTS
2
Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H
2
O
2
-induced cells (
P
<0.01). Compared with the control group, MDA content, ROS level, mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly, while SOD activity, MMP, mRNA expressions of xCT, GPX4 and FTH as well as protein expression
s of GPX4 and FTH were decreased or down-regulated significantly (
P
<0.01 or
P
<0.05). Compared with the H
2
O
2
group, oxidative stress indexes of H
2
O
2
+PL 25, 50 μg/mL groups were reversed to different extents, MMP level was increased significantly, as well as mRNA and protein expressions of Nrf2, HO-1, NQO-1, xCT, GPX4 and FTH were up-regulated to different extents; there were statistical significances in some indexes between groups (
P
<0.01 or
P
<0.05).
CONCLUSIONS
2
PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H
2
O
2
, which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.
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