| 卢瑾,马云枝,宁允帆,等.隐丹参酮调控神经细胞铁死亡对小鼠脑梗死损伤的影响[J].安徽医药,2025,29(9):1744-1750. |
| 隐丹参酮调控神经细胞铁死亡对小鼠脑梗死损伤的影响 |
| Effect of cryptotanshinone on ferroptosis of nerve cells in mice with cerebral infarction injury |
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| DOI：10.3969/j.issn.1009-6469.2025.09.010 |
| 中文关键词: 脑梗死 隐丹参酮 铁死亡 氧糖剥夺 |
| 英文关键词: Cerebral infarction Cryptotanshinone Ferroptosis Oxygen and sugar deprivation |
| 基金项目:河南省医学科技攻关计划项目( SBGJ202102187) |
| 作者 | 单位 | E-mail | | 卢瑾 | 河南中医药大学第一临床医学院,河南郑,州 450000
河南中医药大学第一附属医院脑病科,河南郑州 450000 | | | 马云枝 | 河南中医药大学第一附属医院脑病科,河南郑州 450000 | | | 宁允帆 | 河南中医药大学第一临床医学院,河南郑,州 450000
河南中医药大学第一附属医院脑病科,河南郑州 450000 | | | 周娇 | 河南中医药大学第一临床医学院,河南郑,州 450000
河南中医药大学第一附属医院脑病科,河南郑州 450000 | | | 沈晓明 | 河南中医药大学第一附属医院脑病科,河南郑州 450000 | sxmdoc@126.com |
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| 中文摘要: |
| 目的探讨隐丹参酮(CTS)调节神经细胞 PC12铁死亡对小鼠脑梗死损伤的影响。方法 2022年 12月至 2023年 10月，将 PC12细胞分为细胞对照组、氧-糖剥夺( OGD)模型组、 CTS(1，5，10 μmol/L)组。将 110只 C57BL/6小鼠分为假手术组、大脑中动脉栓塞(MCAO)模型组、 CTS(5，10，20 mg/kg)组，每组 22只。使用细胞计数试剂盒 -8(CCK-8)检测 PC12细胞存活率， Beyo‐Click. 5-溴-2-脱氧尿嘧啶( EdU)-555细胞增殖试剂盒检测 PC12细胞增殖，乳酸脱氢酶( LDH)检测试剂盒检测 PC12细胞 LDH释放率。采用 2，7-二氯荧光素二乙酸酯( DCFH-DA)荧光探针法检测 PC12细胞和 MCAO小鼠脑组织中活性氧( ROS)水平。酶联免疫吸附分析( ELISA)试剂盒测定 PC12细胞和小鼠脑组织中丙二醛( MDA)、肿瘤坏死因子 α(TNF-α)、白细胞介素 -1β(IL-1β)、白细胞介素 -6(IL-6)和 Fe2+水平。蛋白质印迹法测定 PC12细胞和小鼠脑组织中溶质载体家族 7成员 11(SCL7A11)、谷胱甘肽过氧化物酶 4(GPX4)和转铁蛋白受体 1(TFR1)蛋白表达水平。采用 2，3，5-氯化三苯基四氮唑( TTC)染色法评价脑梗死体积。结果与细胞对照组相比， OGD模型组 PC12细胞存活率( 17.47±5.50)%降低， LDH释放率( 74.07± 5.95)%增加(均 P<0.05)。与 OGD模型组相比， CTS(1，5，10 μmol/L)组细胞存活率［( 31.95±2.89)%，(46.24±5.78)%，(58.39± 8.32%)］显著提高， LDH释放率［( 62.73±3.23)%，(53.6±3.63)%，(36.23±4.46)%)］降低(均 P<0.05)。 OGD模型组 ROS水平(DCFH-DA荧光强度)增至( 8.74±1.37)OD，MDA水平升至( 0.41±0.06)μmol/L，Fe2.水平达( 5.6±0.98)μmol/L；CTS 10 μmol/L组显著逆转上述指标［ROS(2.79±0.76)OD；MDA(0.18±0.03)μmol/L；Fe2.(2.5±0.36)μmol/L)］。 MCAO模型组脑梗死体积百分比为( 56.67±9.33)%，CTS 20 mg/kg组降至( 12.13±2.42)%(P<0.05)。此外， CTS(10 μmol/L)显著上调 GPX4(0.95±0.15 vs. 0.17±0.05)和 SCL7A11(1.23±0.09 vs. 0.21±0.02)蛋白表达，并降低 TFR1(0.39±0.05 vs. 1.86±0.13)及炎症因子［TNF-α(23.99±2.19)pg/ L vs.(51.32±2.91)pg/L；IL-6(21.56±2.46)pg/L vs.(41.3±2.62)pg/L］。结论 CTS对脑梗死小鼠脑组织损伤具有保护作用，作用机制可能与其抑制神经细胞铁死亡有关。 |
| 英文摘要: |
| Objective To investigate the effect of cryptotanshinone (CTS) on ferroptosis of PC12 nerve cells in mice with cerebral in-farction injury.Methods PC12 cells were divided into cell control group, oxygen-sugar deprivation (OGD) model group and CTS (1, 5,10 μmol/L) group from December 2022 to October 2023. Ten C57BL/6 mice were split into three groups: twenty-two mice each for the sham operation group, the middle cerebral artery occlusion (MCAO) model group, and the CTS (5, 10, 20 mg/kg) group. PC12 cell sur-vival rate was measured with CCK-8 kit, PC12 cell proliferation was measured with BeyoClick. EdU-555 cell proliferation kit, and lac-tate dehydrogenase (LDH) release rate was measured with LDH test kit. Reactive oxygen species (ROS) levels in PC12 cells and micebrain tissues were detected by 2'-7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The levels of malondialde-hyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and Fe2+ in PC12 cells and mice brain tis-sues were determined by enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of glutathione peroxidase 4 (GPX4),transferrin receptor protein 1 (TFR1), and solute carrier family 7 member 11 (SCL7A11) in PC12 cells and mouse brain tissues were as-sessed using Western blotting analysis. 2,3,5-triphenyltetrazolium chloride (TTC) staining of brain tissue was used to evaluate the vol-ume of cerebral infarction. Results Compared with the control group, the survival rate of PC12 cells in the OGD model group de-creased to 17.47%±5.50%, while the LDH release rate increased to 74.07%±5.95% (all P<0.05). CTS (1, 5, 10 μmol/L) groups showedincreased survival rates (31.95%±2.89%, 46.24%±5.78%, 58.39%±8.32%) and reduced LDH release (62.73%±3.23%, 53.6%±3.63%,36.23%±4.46%) (all P<0.05). OGD elevated ROS (8.74±1.37) OD, MDA (0.41±0.06) μmol/L, and Fe2. (5.6±0.98) μmol/L, which werereversed by 10 μmol/L CTS [ROS: (2.79±0.76) OD; MDA: (0.18±0.03) μmol/L; Fe2.: (2.5±0.36) μmol/L]. The cerebral infarction vol-ume in MCAO mice was 56.67%±9.33%, reduced to 12.13%±2.42% by 20 mg/kg CTS (P<0.05). Furthermore, 10 μmol/L CTS upregu-lated GPX4 (0.95±0.15 vs. 0.17±0.05) and SCL7A11 (1.23±0.09 vs. 0.21±0.02), downregulated TFR1 (0.39±0.05 vs. 1.86±0.13), and decreased inflammatory cytokines [TNF-α: (23.99±2.19) pg/L vs. (51.32±2.91) pg/L; IL-6: (21.56±2.46) pg/L vs. (41.3±2.62) pg/L].Con. clusion CTS has protective effect on brain tissue injury in mice with cerebral infarction, and its mechanism may be related to inhibit-ing ferroptosis of nerve cells. |
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