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microRNA-214-3p 通过抑制组织蛋白酶 B 减轻 LPS 诱导的心肌细胞损伤。

MicroRNA-214-3p Ameliorates LPS-Induced Cardiomyocyte Injury by Inhibiting Cathepsin B.

机构信息

The First Affiliated Hospital, Department of Cardiovascular Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.

出版信息

Folia Biol (Praha). 2022;68(2):78-85. doi: 10.14712/fb2022068020078.

Abstract

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.

摘要

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。

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