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柿叶提取物对H O 诱导IEC-6细胞铁死亡的影响及机制研究 Δ
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张雪侠 ,周 敏 ,周红艳 ,王莉飞 ,李华妮 ,刘长河 ,徐洪德 ,张明利 (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)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2025)01-0064-07
DOI 10.6039/j.issn.1001-0408.2025.01.11
摘 要 目的 探讨柿叶(PL)提取物对过氧化氢(H2O2 )诱导IEC-6细胞铁死亡的影响及潜在机制。方法 以IEC-6细胞为对象,考
察铁死亡抑制剂 ferrostatin-1 对 H2O2诱导 IEC-6 细胞活力的影响;将 IEC-6 细胞分为对照组、H2O2组、H2O2+PL 25 μg/mL 组、H2O2+
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
铁死亡抑制剂 ferrostatin-1 可显著升高 H2O2诱导细胞的存活率(P<0.01)。与对照组比较,H2O2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H2O2组比较,H2O2+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 PL 提取物能减轻 H2O2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。
关键词 柿叶提取物;溃疡性结肠炎;铁死亡;Nrf2/HO-1信号通路
Effects and mechanism of persimmon leaf extract on IEC-6 cell ferroptosis induced by H2O2
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ZHANG Xuexia ,ZHOU Min ,ZHOU Hongyan ,WANG Lifei ,LI Huani ,LIU Changhe ,XU Hongde ,
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ZHANG Mingli(1. Institute of Chinese Medicine, Henan Integrative Medicine Hospital, Zhengzhou 450004,
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China;2. School of Pharmacy, Zhengzhou University, Zhengzhou 450001, China;3. Dept. of Clinical
Laboratory, Henan Integrative Medicine Hospital, Zhengzhou 450004, China;4. Dept. of Nephropathy, Second
Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China;5. Dept. of Pulmonary, Henan
Integrative Medicine Hospital, Zhengzhou 450004, China)
ABSTRACT OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf (PL) extract against ferroptosis
induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object, the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6
cell viability induced by H2O2 were investigated; IEC-6 cells were divided into control group, H2O2 group, H2O2+PL 25 μg/mL
group and H2O2+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 Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-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 expressions of GPX4 and FTH were decreased or down-regulated significantly (P<0.01 or
P<0.05). Compared with the H2O2 group, oxidative stress
Δ 基金项目 河南省自然科学基金项目(No.242300420426);河南 indexes of H2O2+PL 25, 50 μg/mL groups were reversed to
省医学科技攻关计划项目(No.LHGJ20230676);河南省中西医结合医
different extents, MMP level was increased significantly, as
院基本科研业务费立项项目(No.2404041,No.2404049) well as mRNA and protein expressions of Nrf2, HO-1, NQO-1,
*第一作者 助理研究员,硕士。研究方向:中药药理及药效物质
xCT, GPX4 and FTH were up-regulated to different extents;
基础。E-mail:343499957@qq.com
# 通信作者 主任医师,硕士。研究方向:呼吸与消化系统疾病的 there were statistical significances in some indexes between
中医治疗。E-mail:Zhang120@126.com groups (P<0.01 or P<0.05). CONCLUSIONS PL extract
· 64 · China Pharmacy 2025 Vol. 36 No. 1 中国药房 2025年第36卷第1期