Li Jun, Wang Hao, Chen Li, Zhong Jialin, Wang Junsheng, Xiao Jun
Department of Cardiovascular Medicine, Chongqing University Center Hospital, Chongqing, People's Republic of China.
Ann Med Surg (Lond). 2023 Aug 7;85(10):4844-4850. doi: 10.1097/MS9.0000000000001139. eCollection 2023 Oct.
A major consequence of acute myocardial infarction is myocardial ischemia-reperfusion (I/R) injury. Collecting proof demonstrates that AXIN1 assume a basic part in different disease; however, the role of AXIN1 in I/R injury remains to a great extent obscure.
The I/R injury model on AC16 cells was constructed. siRNA transfection was used to knockdown AXIN1. The qRT-PCR assays and western blot assays were used to detect the expression level of AXIN1 and other key proteins. CCK-8 assays and cell apoptosis assays were used to detect cell proliferation and cell apoptosis.
AXIN1 was significantly overexpressed in an in vitro model of I/R injury. Knockdown of AXIN1 significantly restored the cell proliferation inhibition caused by IR injury, while inhibiting apoptosis and inflammation. Further mechanistic studies revealed that the transcription factor c-Myc could regulate the expression of AXIN1. The effects of I/R injury on AC16 cells after overexpression of c-Myc were reversed by knockdown of AXIN1. Meanwhile, AXIN1 could regulate the SIRT1/p53/Nrf 2 pathway.
Our results show an important role for AXIN1 and provide new targets for avoiding and treating I/R injury.
急性心肌梗死的一个主要后果是心肌缺血再灌注（I/R）损伤。越来越多的证据表明，AXIN1在多种疾病中起关键作用；然而，AXIN1在I/R损伤中的作用在很大程度上仍不清楚。
构建AC16细胞的I/R损伤模型。使用小干扰RNA（siRNA）转染来敲低AXIN1。采用实时定量聚合酶链反应（qRT-PCR）检测和蛋白质免疫印迹检测来检测AXIN1及其他关键蛋白的表达水平。使用细胞计数试剂盒-8（CCK-8）检测和细胞凋亡检测来检测细胞增殖和细胞凋亡。
在I/R损伤的体外模型中AXIN1显著过表达。敲低AXIN1可显著恢复由缺血再灌注损伤引起的细胞增殖抑制，同时抑制细胞凋亡和炎症。进一步的机制研究表明，转录因子c-Myc可以调节AXIN1的表达。过表达c-Myc后缺血再灌注损伤对AC16细胞的影响可通过敲低AXIN1来逆转。同时，AXIN1可以调节沉默信息调节因子2相关酶1（SIRT1）/p53/核因子E2相关因子2（Nrf 2）通路。
我们的结果显示了AXIN1的重要作用，并为避免和治疗I/R损伤提供了新的靶点。
