Physiology Research Center, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Mol Biol Rep. 2021 Apr;48(4):3337-3348. doi: 10.1007/s11033-021-06359-0. Epub 2021 Apr 25.
Human amniotic membrane mesenchymal stem cells-derived conditioned medium (hAM-MSCs-CM) has positive effects against myocardial ischemia/reperfusion (MI/R) injury. However, it needs further investigations how hAM-MSCs-CM leads to the cell survival under MI/R via modulation of autophagy. The purpose of this study is investigating the effects of hAM-MSCs-CM in a rat model of MI/R injury by focusing on the role of autophagy as one of its possible mechanisms. Male Wistar rats (44 rats, 175-200 g) were randomly divided into four groups: Sham, MI/R, culture media-receiving and conditioned medium-receiving. MI/R was induced by 30 min of left anterior descending coronary artery ligation. After 15 min reperfusion, culture media or hAM-MSCs-CM (150 μl) were injected intramyocardially. At the end of the experiment, CK-MB, autophagy markers, phosphorylated and total forms of mTOR and ULK1, cardiac function and fibrosis were measured. hAM-MSCs-CM significantly decreased CK-MB levels (P < 0.0001), and also the mRNA levels of Beclin1 (P < 0.0001), LC3 (P = 0.012) and p62 (P = 0.003). In addition, hAM-MSCs-CM significantly reduced Beclin1, LC3II/LC3I and p62 protein levels (P < 0.0001), and increased p-mTOR/mTOR (P = 0.022) and p-ULK1/ULK1 (P < 0.0001) expressions. Moreover, hAM-MSCs-CM improved cardiac function and decreased fibrosis (P < 0.0001). This study showed cardioprotective effects of hAM-MSCs-CM against MI/R injury through modulation of autophagy via mTOR/ULK1 pathway. Based on these findings, it can be concluded that hAM-MSCs-CM can be offered as an attractive candidate for attenuation of MI/R injury in future, but needs further investigations.
人羊膜间充质干细胞条件培养基（hAM-MSCs-CM）对心肌缺血/再灌注（MI/R）损伤具有积极作用。然而，hAM-MSCs-CM 通过调节自噬如何导致 MI/R 下的细胞存活，还需要进一步研究。本研究旨在通过关注自噬作为其可能机制之一，在 MI/R 损伤大鼠模型中研究 hAM-MSCs-CM 的作用。雄性 Wistar 大鼠（44 只，175-200g）随机分为四组：假手术组、MI/R 组、培养基组和条件培养基组。通过结扎左前降支 30min 诱导 MI/R。再灌注 15min 后，心肌内注射培养基或 hAM-MSCs-CM（150μl）。实验结束时，测定 CK-MB、自噬标志物、磷酸化和总形式的 mTOR 和 ULK1、心功能和纤维化。hAM-MSCs-CM 显著降低 CK-MB 水平（P<0.0001），并降低 Beclin1（P<0.0001）、LC3（P=0.012）和 p62（P=0.003）mRNA 水平。此外，hAM-MSCs-CM 显著降低 Beclin1、LC3II/LC3I 和 p62 蛋白水平（P<0.0001），增加 p-mTOR/mTOR（P=0.022）和 p-ULK1/ULK1（P<0.0001）表达。此外，hAM-MSCs-CM 改善心功能，减少纤维化（P<0.0001）。本研究表明，hAM-MSCs-CM 通过 mTOR/ULK1 通路调节自噬对 MI/R 损伤具有心脏保护作用。基于这些发现，可以得出结论，hAM-MSCs-CM 可以作为未来减轻 MI/R 损伤的有吸引力的候选物，但需要进一步研究。
