Effects of Mitochondrial ATP-Sensitive Potassium Channel in Rats with Acute Myocardial Infarction and Its Association with the AKT/mTOR Pathway.
Effects of Mitochondrial ATP-Sensitive Potassium Channel in Rats with Acute Myocardial Infarction and Its Association with the AKT/mTOR Pathway.
复制标题
急性心肌梗死大鼠线粒体ATP敏感钾通道的作用及其与AKT/mTOR通路的关系
DOI：
10.14744/anatoljcardiol.2022.2406
复制
发表时间：
2023-02
影响因子：
1.3
通讯作者：
中科院分区：
文献类型：
--
作者：
心肌梗死与心肌细胞的自噬和凋亡有关，蛋白激酶B/哺乳动物雷帕霉素靶蛋白（AKT/mTOR）通路在其中起着重要作用。急性心肌梗死大鼠模型在诱导心肌梗死后0.5、2、4和6小时使用苏木精和伊红染色、氯化三苯基四氮唑染色、心肌酶测量和自噬活性水平进行评估。此外，在心肌损伤高峰期向大鼠模型腹膜内给予二氮嗪、5-羟基癸酸酯和LY 294002，以评估其对心脏损伤的影响。测量自噬相关和凋亡相关蛋白以及p-AKT和p-mTOR的表达水平。电镜观察心肌组织超微结构和自噬体的数量。我们证明，与对照组相比，实验组的心肌损伤程度和自噬水平显著升高。此外，与未治疗的大鼠相比，二氮嗪治疗的急性心肌梗死大鼠的心肌梗死面积显著较小。二氮嗪还可降低急性心肌梗死大鼠心肌损伤标志物、自噬和细胞凋亡水平，诱导AKT和mTOR磷酸化水平，减少自噬体数量，改善心肌超微结构。5-羟基癸酸酯治疗导致与二氮嗪治疗后观察到的效果相反。LY 294002也能够逆转二氮嗪治疗效果。在大鼠急性心肌梗死诱导后2小时观察到心肌组织损伤和自噬的峰值水平。二氮嗪治疗抑制心肌自噬和细胞凋亡，同时保护心脏组织免受缺血性损伤，这可能是通过激活AKT/mTOR途径进行的。
Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.
影响因子：
5
作者：
Bodiga, Sreedhar;Zhang, Rong;Jacobs, Dexter E.;Larsen, Brandon T.;Tampo, Akihito;Manthati, Vijay L.;Kwok, Wai-Meng;Zeldin, Darryl C.;Falck, John R.;Gutterman, David D.;Jacobs, Elizabeth R.;Medhora, Meetha M.
通讯作者：
Medhora, Meetha M.