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[1]林强,李洪伟,郭开今,等.咖啡酸苯乙酯通过Nrf-2 途径抑制地塞米松诱导的成骨细胞凋亡[J].医学研究与战创伤救治(原医学研究生学报),2017,19(02):126-131.[doi:10.3969/j.issn.1672-271X.2017.02.004]
　LIN Qiang,LI Hong-wei,GUO Kai-jin,et al.Caffeic acid phenethyl ester inhibits the apoptosis induced by dexamethasone via the regulation of Nrf-2 pathway in osteoblasts[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2017,19(02):126-131.[doi:10.3969/j.issn.1672-271X.2017.02.004]
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咖啡酸苯乙酯通过Nrf-2 途径抑制地塞米松诱导的成骨细胞凋亡()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第19卷
期数:
2017年02期
页码:
126-131
栏目:
出版日期:
2017-03-20

文章信息/Info

Title:
Caffeic acid phenethyl ester inhibits the apoptosis induced by dexamethasone via the regulation of Nrf-2 pathway in osteoblasts
作者:
林强1; 李洪伟2; 郭开今2; 周冰2; 李东亚2
1.221004徐州，徐州医科大学研究生学院； 2. 221002徐州，徐州医科大学附属医院骨科
Author(s):
LIN Qiang1;  LI Hong-wei2; GUO Kai-jin2; ZHOU Bing2;  LI Dong-ya2
(1.Graduate School, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; 2. Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China)
关键词:
咖啡酸苯乙酯; 地塞米松; 成骨细胞; Nrf-2信号通路; 细胞凋亡
Keywords:
Caffeic acid phenethyl ester;  Dexamethasone;  Osteoblast cell;  Nrf-2 pathway;  Apoptosis
分类号:
R681
DOI:
10.3969/j.issn.1672-271X.2017.02.004
文献标志码:
A
摘要:
目的 探讨Nrf-2途径在咖啡酸苯乙酯（CAPE）抑制地塞米松（DEX）诱导成骨细胞凋亡中的作用。方法 用细胞贴壁法培养小鼠颅顶前骨细胞（MC3T3-E1），采用10μmol/L DEX建立细胞损伤模型，以不同浓度CAPE(0.05、0.25、1μmol/L)预处理细胞2h后加入地塞米松共孵育24h；细胞增殖-毒性检测试剂盒（CCK-8）检测细胞增殖活性；依据CCK-8检测结果 确定药物浓度后将实验分为对照组、咖啡酸苯乙酯组（CAPE组）、地塞米松组（DEX组），咖啡酸苯乙酯+地塞米松组（CAPE+DEX组）；DCFH-DA荧光探针检测细胞内活性氧（reactive oxygen species， ROS）水平；Caspase-3活性检测试剂盒检测Caspase-3酶活性，Western blot法检测Nrf-2 途径相关蛋白Nrf-2和血红素氧合酶1（heme oxygenase，HO-1）蛋白表达水平；流式细胞仪检测细胞凋亡率。结果 10μmol/L DEX作用下细胞形态发生明显变化，损伤作用明显。与对照组相比，DEX组内细胞存活率显著下降（P＜0.01），而细胞内 ROS水平、细胞凋亡率及Caspase-3酶活性显著增加（P＜0.01）；同时，Nrf-2途径相关蛋白 Nrf-2及HO-1表达量减少，差异有统计学意义（P＜0.01）。与DEX组相比，CAPE+DEX组细胞存活率显著上升（P＜0.01），Nrf-2途径相关蛋白 Nrf-2及HO-1表达明显增加（P＜0.01）；此外，CAPE+DEX组细胞内 ROS 水平、细胞凋亡率及Caspase-3酶活显著降低，差异有统计学意义（P＜0.01）。结论 咖啡酸苯乙酯可以通过Nrf-2途径降低细胞内ROS水平进而减轻地塞米松诱导的氧化应激所致细胞损伤及凋亡。
Abstract:
Objective To explore the effect of caffeic acid phenethyl ester (CAPE) on the apoptosis of MC3T3-E1 preosteoblasts induced by dexamethasone (DEX).Methods MC3T3-E1 cells were exposed to DEX (10 μmol/L) to establish a model of osteoblast injury. The incubated MC3T3-E1 cells were pretreated with various concentrations of CAPE for 2 hours, and then cultured in combination with 10 μmol/L DEX for 24 hours. Cell proliferation was evaluated by cell count kit (CCK-8). The final concentration of drug was determined by the Results of CCK-8, then cells randomly divided into four groups: Control group, CAPE group, DEX group, and CAPE+DEX group. Cell apoptosis rate was detected by Annexin V-FITC/PI staining and flow cytometry in each group. Caspase-3 activity was monitored by Caspase-3 activity assay kit; Intracelluar ROS was detected by DCFH-DA fluorescence staining．The expressions of Nrf-2 and HO-1 were examined by Western blot.Results Dexamethasone could induced MC3T3-E1 cell injury with overt morphological and cell activity changes at 24 hours, especially the 10 μmol/L DEX. Compared with control group, and the cell activi-ty was decreased significantly (P<0.01), while the level of intracellular ROS, cell apoptosis rate and Caspase-3 activity increased significantly (P<0.01). Moreover, the Nrf-2 and HO-1 was decreased significantly (P<0.01). Compare with DEX group, expression of Nrf-2 and HO-1 (P<0.01 vs DEX group) in CAPE+DEX group were significantly increased (P<0.01). In addition, the levels of ROS, apoptosis and Caspase-3 activity were significantly lower in the CAPE+DEX group (P<0.01).Conclusion CAPE inhibits the level of ROS in osteoblasts via regulating Nrf-2 pathway, resulting in the reduction of apoptosis induced by dexamethasone.

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备注/Memo

备注/Memo:
基金项目：徐州市科学技术局项目(KCl4SHl02)
更新日期/Last Update: 2017-03-20