轻链型心肌淀粉样变是一种致死性浆细胞病。我们在前期工作中发现，致淀粉样变轻链(AL-LC)可使心肌细胞自噬和凋亡水平显著上升；初步机制研究亦证实AL-LC可下调miR-125b的表达，且ATM可能是miR-125b的靶基因。据此我们提出科学假说：AL-LC可抑制心肌细胞miR-125b的表达，导致miR-125b下游靶基因ATM高表达，从而通过TSC2/mTOR通路增加心肌细胞的自噬水平，并最终诱导心肌细胞凋亡。因此，我们拟研究miR-125b在心肌细胞自噬和凋亡中的作用，验证miR-125b的靶基因，并探讨其靶基因对下游TSC2/mTOR通路的调控及相关分子机制；此外，我们拟分析轻链型心肌淀粉样变患者心肌组织的自噬和凋亡水平，以及miR-125b和ATM的表达异常；以期揭示AL-LC导致轻链型心肌淀粉样变的发病机制。本研究成果可为轻链型心肌淀粉样变治疗新技术的研发提供新的思路和实验依据。

Light-chain cardiac amyloidosis is a lethal plasma cell dyscrasia. Our previous study discovered that amyloid light chain (AL-LC) significantly increased the autophagy and apoptosis in cardiomyocytes. Preliminary study showed that the level of miR-125b was downregulated by AL-LC, and ATM gene might be a potential target gene of miR-125b. Therefore, we hypothesize that AL-LC can inhibit the expression of miR-125b in cardiomyocytes, and thus upregulate its downstream ATM gene, which consequently induce autophagy through the TSC2/mTOR pathway and finally lead to the apoptosis of cardiomyocytes. Accordingly, we plan to study the role of miR-125b in the autophagy and apoptosis of myocardial cells, demonstrate the target gene of miR-125b, and reveal its regulation on the downstream TSC2/mTOR pathway. Meanwhile, we intend to investigate into the expression of miR-125b and ATM in the myocardial tissue of patients with light-chain cardiac amyloidosis, and its impact on autophagy and apoptosis, thus revealing the role of AL-LC induced autophagy in the pathogenesis of light-chain cardiac amyloidosis. The findings of this study may provide new ideas and experimental evidence for developing novel therapies for light-chain cardiac amyloidosis.