Zuo YaBei, Wang YuZhao, Hu HaiJuan, Cui Wei
Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Cell Physiol Biochem. 2016;39(3):1021-30. doi: 10.1159/000447809. Epub 2016 Aug 19.
This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism.
Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry.
Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level.
These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.
本研究旨在评估阿托伐他汀对心肌细胞缺血/再灌注（I/R）损伤的保护作用及其可能的潜在机制。
评估了有或没有阿托伐他汀预处理的氧糖剥夺/复氧（OGD/R）对心肌细胞的直接细胞毒性作用。使用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法测定阿托伐他汀对糖原合成酶激酶-3β（GSK-3β）和微小RNA-199a-5p（miR-199a-5p）表达的影响。此外，使用RT-PCR、蛋白质免疫印迹法和免疫组织化学检测miR-199a-5p上调和下调时的GSK-3β表达。
阿托伐他汀预处理显著提高了OGD/R后细胞活力的恢复（p<0.05）。此外，阿托伐他汀预处理显著增加了GSK-3β在mRNA水平和蛋白质水平的表达，并降低了miR-199a-5p在mRNA水平的表达（p<0.05）。miR-199a-5p的上调和下调分别降低和增加了GSK-3β在mRNA水平和蛋白质水平的表达。
这些结果表明，阿托伐他汀通过抑制miR-199a-5p增加GSK-3β的表达，从而对I/R损伤起到心脏保护作用。
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