Zhou Haiyan, Mo Lili, Huang Niwen, Zou Changchao, Li Chao, Lin Muzhi, Zhang Bei, Wei Bo, Li Ping, Si Xiaoyun, Chen Jingjing, Li Wei, Liu Xingde, Hu Bailong
Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Department of Cardiovascular Medicine, Guizhou Qiannan People's Hospital, Duyun, China.
Ann Transl Med. 2022 Feb;10(4):168. doi: 10.21037/atm-21-7041.
This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms.
A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time points. A further 30 adult male Sprague-Dawley rats were randomized and divided into the following 3 groups (n=10 in each group): sham operation, ischemia/reperfusion (I/R), and I/R + T1AM. In the I/R and I/R + T1AM groups, the left anterior descending (LAD) coronary artery of the rats were occluded for 0.5 hour to induce myocardial ischemia, followed by reperfusion for 3 hours in the I/R group. The electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were examined in rats to evaluate the myocardial injury. The differences in the expression of apoptosis-related and Akt-FoxO1 signaling-related proteins were determined via Western blot.
This work verified that T1AM reduced the body temperature of rats in a dose-dependent manner. Additionally, T1AM improved cardiac function and decreased the infarction size caused by MIRI. T1AM reduced the expression of biochemical parameters and apoptosis of myocardial cells. In addition, after treatment with T1AM, the expression of Glut1, pFoxO1 and Akt were reduced, while the expression of FoxO1 and PPARα were increased significantly.
Pretreatment of cardiomyocytes with T1AM inhibited apoptosis and protected against ischemia reperfusion injury via the Akt/FoxO1 signaling pathway.
本研究调查了3-碘甲腺原氨酸（T1AM）对心肌缺血再灌注损伤（MIRI）的潜在影响及其潜在分子机制。
将16只成年雄性Sprague-Dawley大鼠随机分为4组，并给予以下处理：对照组[60%二甲基亚砜（DMSO）和40%生理盐水，pH 7.4]、25 mg/kg T1AM、50 mg/kg T1AM或100 mg/kg T1AM。在不同时间点测量大鼠的直肠温度。另外30只成年雄性Sprague-Dawley大鼠被随机分为以下3组（每组n = 10）：假手术组、缺血/再灌注（I/R）组和I/R + T1AM组。在I/R组和I/R + T1AM组中，阻断大鼠左冠状动脉前降支（LAD）0.5小时以诱导心肌缺血，然后I/R组再灌注3小时。检测大鼠的心电图（ECG）、心功能和2,3,5-三苯基氯化四氮唑（TTC）染色以评估心肌损伤。通过蛋白质免疫印迹法测定凋亡相关蛋白和Akt-FoxO1信号相关蛋白表达的差异。
本研究证实T1AM以剂量依赖方式降低大鼠体温。此外，T1AM改善了心功能并减小了MIRI引起的梗死面积。T1AM降低了生化参数的表达和心肌细胞凋亡。此外，用T1AM处理后，Glut1、pFoxO1和Akt的表达降低，而FoxO1和PPARα的表达显著增加。
用T1AM预处理心肌细胞可抑制细胞凋亡，并通过Akt/FoxO1信号通路预防缺血再灌注损伤。
