The First Affiliated Hospital, Department of Cardiovascular Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
Folia Biol (Praha). 2022;68(2):78-85. doi: 10.14712/fb2022068020078.
Myocardial injury is a common complication of sepsis. MicroRNA (miRNA) miR-214-3p is protective against myocardial injury caused by sepsis, but its mechanism in lipopolysaccharide (LPS)- induced cardiomyocyte injury is still unclear. An AC16 cell injury model was induced by LPS treatment. Cell Counting Kit-8 and flow cytometry assay showed decreased cell viability and increased apoptosis in LPS-treated AC16 cells. The levels of caspase- 3, Bax, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), myosin 6 (Myh6), myosin 7 (Myh7), reactive oxygen species (ROS), and malondialdehyde (MDA) were increased in LPS-treated AC16 cells, but the levels of Bcl-2 and superoxide dismutase (SOD) were decreased. MiR-214-3p was down-regulated and cathepsin B (CTSB) was upregulated in LPS-treated AC16 cells. At the same time, miR-214-3p could target CTSB and reduce its expression. We also found that a miR-214-3p mimic or CTSB silencing could significantly reduce LPSinduced apoptosis, decrease ROS, MDA, caspase-3, and Bax and increase SOD and Bcl-2. CTSB silencing could significantly reduce ANP, BNP, Myh6, and Myh7 in LPS-treated AC16 cells. The effects of CTSB silencing were reversed by a miR-214-3p inhibitor. In summary, miR-214-3p could inhibit LPSinduced myocardial injury by targeting CTSB, which provides a new idea for myocardial damage caused by sepsis.
心肌损伤是脓毒症的常见并发症。微小 RNA (miRNA) miR-214-3p 对脓毒症引起的心肌损伤具有保护作用,但它在脂多糖 (LPS) 诱导的心肌细胞损伤中的作用机制尚不清楚。通过 LPS 处理诱导 AC16 细胞损伤模型。细胞计数试剂盒-8 和流式细胞术检测显示 LPS 处理的 AC16 细胞活力降低,细胞凋亡增加。LPS 处理的 AC16 细胞中 caspase-3、Bax、心房利钠肽 (ANP)、脑利钠肽 (BNP)、肌球蛋白 6 (Myh6)、肌球蛋白 7 (Myh7)、活性氧 (ROS) 和丙二醛 (MDA) 水平升高,但 Bcl-2 和超氧化物歧化酶 (SOD) 水平降低。miR-214-3p 在 LPS 处理的 AC16 细胞中下调,组织蛋白酶 B (CTSB) 上调。同时,miR-214-3p 可以靶向 CTSB 并降低其表达。我们还发现 miR-214-3p 模拟物或 CTSB 沉默可以显著减少 LPS 诱导的细胞凋亡,减少 ROS、MDA、caspase-3 和 Bax,增加 SOD 和 Bcl-2。CTSB 沉默可以显著减少 LPS 处理的 AC16 细胞中的 ANP、BNP、Myh6 和 Myh7。miR-214-3p 抑制剂可以逆转 CTSB 沉默的作用。综上所述,miR-214-3p 可以通过靶向 CTSB 抑制 LPS 诱导的心肌损伤,为脓毒症引起的心肌损伤提供了新的思路。