槲皮素通过 SIRT1/PGC-1α 信号通路改善缺血/再灌注诱导的心肌细胞凋亡的体内外研究。
Quercetin improve ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro and in vivo study via SIRT1/PGC-1α signaling.
机构信息
Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Anesthesiology, Xi'an Children's Hospital, Xi'an, China.
出版信息
J Cell Biochem. 2019 Jun;120(6):9747-9757. doi: 10.1002/jcb.28255. Epub 2019 Jan 17.
AIM
To evaluate the effects of quercetin to improve ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro and in vivo study.
METHODS
The cells were divided into five groups: model control (MC) group was ischemia/reperfusion (I/R) model group; DL group was treated with 25 mL/L quercetin based on MC group; DM group was treated with 50 ml/L quercetin based on MC group; DH group was treated with 100 mL/L quercetin based on MC group; Meto group was treated with metoprolol based on MC group. In the in vivo study, the rats were divided into five groups: MC group was I/R model group; DL group was treated with 25 mg/kg quercetin; DM group was treated with 50 mg/kg quercetin; DM group was treated with 100 mg/kg quercetin; Meto group was treated with Meto as positive drug.
RESULTS
The cell apoptosis rates of quercetin treated groups (DL, DM, and DH groups) were significantly suppressed compared with the MC group. The silent information regulatory factor 1 (SIRT1), peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), and Bcl-2 proteins expression of quercetin treated were significantly upregulation compared with MC group (P < 0.05, respectively), and Bax protein expression of quercetin treated group was significantly downregulation compared with MC group ( P < 0.05, respectively). In the vivo study, the myocardial pathological morphology of quercetin treated groups was improved. The cell apoptosis number of quercetin treated group were significantly suppressed compared with MC group by terminal deoxynucleotidyl transferase dUTP nick end labeling assay ( P < 0.05, respectively). SIRT1, PGC-1a, Bcl-2, and Bax proteins expressions of quercetin treated groups were significant differences compared with MC group in myocardial tissue ( P < 0.05, respectively).
CONCLUSION
Quercetin had improved the myocardial ischemia/reperfusion-induced cardiomyocyte apoptosis via SIRT1/PGC-1α signaling.
目的
评估槲皮素对体外和体内缺血/再灌注诱导的心肌细胞凋亡的影响。
方法
细胞分为五组：模型对照组（MC）为缺血/再灌注（I/R）模型组；DL 组为 MC 组基础上加用 25mmol/L 槲皮素；DM 组为 MC 组基础上加用 50mmol/L 槲皮素；DH 组为 MC 组基础上加用 100mmol/L 槲皮素；Meto 组为 MC 组基础上加用美托洛尔。在体内研究中，大鼠分为五组：MC 组为 I/R 模型组；DL 组给予 25mg/kg 槲皮素；DM 组给予 50mg/kg 槲皮素；DH 组给予 100mg/kg 槲皮素；Meto 组给予阳性药物美托洛尔。
结果
与 MC 组相比，槲皮素处理组（DL、DM 和 DH 组）的细胞凋亡率明显降低。与 MC 组相比，槲皮素处理组的沉默信息调节因子 1（SIRT1）、过氧化物酶体增殖物激活受体-γ 共激活因子-1α（PGC-1α）和 Bcl-2 蛋白表达明显上调（P<0.05），Bax 蛋白表达明显下调（P<0.05）。在体内研究中，槲皮素处理组的心肌病理形态得到改善。与 MC 组相比，末端脱氧核苷酸转移酶 dUTP 缺口末端标记法（TUNEL）检测显示，槲皮素处理组的细胞凋亡数明显减少（P<0.05）。与 MC 组相比，心肌组织中 SIRT1、PGC-1a、Bcl-2 和 Bax 蛋白表达均有显著性差异（P<0.05）。
结论
槲皮素通过 SIRT1/PGC-1α 信号通路改善心肌缺血/再灌注诱导的心肌细胞凋亡。
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