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·药学研究·
芒果苷对心肌细胞损伤的保护作用及对NFATc4表达的影响
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韦啟球 ,高 思,冯艺萍,裴世成,刘雪萍(广西科技大学医学部药学系,广西 柳州 545005)
*
#
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2023)20-2454-05
DOI 10.6039/j.issn.1001-0408.2023.20.02
摘 要 目的 研究芒果苷对过氧化氢(H2O2 )诱导的心肌细胞氧化应激损伤的保护作用,以及对活化T细胞核因子c4(NFATc4)表
达的影响。方法 体外培养心肌H9c2细胞,分为空白组、H2O2组和芒果苷50、100、150 μmol/L组,芒果苷组细胞在经不同浓度芒果
苷作用 12 h 后,再与 H2O2组一同经 H2O2 (200 μmol/L)刺激 12 h,检测各组细胞的相对存活率,细胞上清液中超氧化物歧化酶
(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)水平,细胞中活性氧(ROS)水平,以及细胞中凋亡相关蛋白[B 细胞淋巴瘤 2(Bcl-2)、
Bcl-2 相关 X 蛋白(Bax)、剪切的胱天蛋白酶 3(cleaved caspase-3)]、核蛋白 NFATc4 的表达情况。转染 NFATc4 干扰序列,考察
NFATc4对H2O2诱导的心肌细胞中氧化应激指标和凋亡相关蛋白的影响。结果 与空白组比较,H2O2组细胞的相对存活率,SOD、
CAT水平,Bcl-2的相对表达量均显著降低;MDA、ROS水平,Bax、cleaved caspase-3和核蛋白NFATc4的相对表达量均显著升高(P<
0.05或P<0.01)。与H2O2组比较,芒果苷100、150 μmol/L组细胞的上述指标均得以显著逆转(P<0.05)。转染NFATc4干扰序列后,
核蛋白NFATc4的表达显著下调,MDA、ROS水平和Bax、cleaved caspase-3蛋白的表达均较H2O2组显著降低/下调,SOD、CAT水平和
Bcl-2蛋白的表达均较H2O2组显著升高/上调(P<0.05)。结论 芒果苷能够减轻H2O2诱导的H9c2细胞氧化应激,减少细胞凋亡,抑制
NFATc4蛋白入核,进而缓解心肌细胞损伤;降低NFATc4蛋白的核内水平与减轻H2O2诱导的氧化应激、细胞凋亡有关。
关键词 芒果苷;H9c2细胞;氧化应激;凋亡;活化T细胞核因子c4
Protective effects of mangiferin against myocardial cell damage and its effects on the expression of NFATc4
WEI Qiqiu,GAO Si,FENG Yiping,PEI Shicheng,LIU Xueping(Dept. of Pharmacy, School of Medicine,
Guangxi University of Science and Technology, Guangxi Liuzhou 545005, China)
ABSTRACT OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells
induced by hydrogen peroxide (H2O2 ), and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4(NFATc4).
METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group, H2O2 group, and 50, 100, 150 μmol/L
mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h, and then were subjected to
H2O2 (200 μmol/L) stimulation for 12 hours together with the H2O2 group; relative survival rate was detected in each group, and
the levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in cell supernatant and reactive oxygen
species (ROS) in H9c2 cells were measured. Meanwhile, the expressions of apoptosis-related proteins [B cell lymphoma 2 (Bcl-
2), Bcl-2 associated X protein (Bax), cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore, the NFATc4
interference sequence was transfected, and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2-
induced myocardial cells were investigated. RESULTS Compared with blank group, relative cell viability, the levels of SOD and
CAT, relative expression of Bcl-2 were decreased significantly, while the levels of MDA and ROS, relative expressions of Bax,
cleaved caspase-3 and nuclear protein NFATc4 were increased significantly (P<0.05 or P<0.01). Compared with the H2O2 group,
the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly (P<0.05). After the transfection of the
NFATc4 interference sequence, the expression of nuclear protein NFATc4 was down-regulated significantly; the levels of MDA and
SOD, the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly, while the levels of
SOD and CAT, and the protein expression of Bcl-2 were all increased/up-regulated significantly, compared with H2O2 group (P<
0.05). CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells, reduce the apoptosis and inhibit the
nuclear translocation of NFATc4, thereby alleviating myocardial cell damage; reducing the nuclear level of NFATc4 protein is
related to reducing H2O2-induced oxidative stress and cell apoptosis.
KEYWORDS mangiferin; H9c2 cells; oxidative stress;
Δ 基金项目 国家自然科学基金项目(No.82160059);广西自然科 apoptosis; nuclear factor of activated T cells cytoplasmic 4
学基金项目(No.2020GXNSFAA259025);广西科技大学博士基金项目
(No.131135) 持续的病理性心脏肥大最终可导致心力衰竭,而病
*第一作者 讲师,硕士。研究方向:天然产物活性。E-mail:
理性心脏肥大的发生和发展被认为是多种复杂因素综
315833134@qq.com [1]
# 通信作者 副研究员,博士。研究方向:心血管药理。E-mail: 合作用的结果 。目前,临床尚缺乏有效手段来延缓或
100000774@gxust.edu.cn 逆转心脏肥大向心力衰竭进展。研究发现,在慢性心力
· 2454 · China Pharmacy 2023 Vol. 34 No. 20 中国药房 2023年第34卷第20期