School of Medicine, Quzhou College of Technology, Quzhou, Zhejiang, China.
Department of Pharmacy, Jiangshan Hospital of Traditional Chinese Medicine, Quzhou, Zhejiang, China.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S29-S38. doi: 10.1177/09603271211025589. Epub 2021 Jul 2.
Myocardial ischemia/reperfusion injury (IRI) is a common perioperative complication of heart and great vessels surgery, aggravating the original myocardial damage and seriously affecting the postoperative recovery of cardiac function. The aim of this study was to reveal the functional effects and potential mechanisms of notoginsenoside R1 (NG-R1) in myocardial cells injured by hypoxia-reoxygenation (H/R).
The rat cardiomyocyte line H9c2 was subjected to H/R with or without NG-R1 treatment. The levels of miR-132 and HBEGF in the cell were altered by microRNA or short-hairpin RNA transfection. Cell viability, apoptosis, lactate dehydrogenase (LDH) and malondialdehyde (MDA) were monitored. Dual luciferin was used to detect the relationship between miR-132 and HBEGF.
NG-R1 20 μM) had no impact on H9c2 cells, but cell viability was significantly reduced at 80 μM. NG-R1 (20 μM) protected H9c2 cells against H/R-induced cell damage, accompanied by increased cell viability, reduced cell apoptosis, and downregulation of LDH and MDA. Furthermore, the level of miR-132 was decreased in response to H/R exposure but then increased after NG-R1 treatment. When miR-132 was overexpressed, H/R-induced cell damage could be recovered. Downregulation of miR-132 limited the protective effect of NG-R1 on H/R damage. We also found that HBEGF was a direct target of miR-132. The expression of HBEGF was increased upon H/R damage, and this increase was reversed after NG-R1 treatment.
This study demonstrated that NG-R1 markedly protected H9c2 cells against H/R-induced damage via upregulation of miR-132 and downregulation of its target protein HBEGF.
心肌缺血/再灌注损伤（IRI）是心脏和大血管手术围手术期常见的并发症，加重了原有心肌损伤，严重影响了心脏功能的术后恢复。本研究旨在揭示三七皂苷 R1（NG-R1）在缺氧/复氧（H/R）损伤心肌细胞中的功能作用及潜在机制。
采用 H/R 处理大鼠心肌细胞系 H9c2，并用 NG-R1 处理。通过 microRNA 或短发夹 RNA 转染改变细胞中 miR-132 和 HBEGF 的水平。监测细胞活力、凋亡、乳酸脱氢酶（LDH）和丙二醛（MDA）。用双荧光素酶检测 miR-132 和 HBEGF 之间的关系。
20 μM 的 NG-R1 对 H9c2 细胞没有影响，但 80 μM 的 NG-R1 则显著降低了细胞活力。NG-R1（20 μM）可保护 H9c2 细胞免受 H/R 诱导的细胞损伤，表现为细胞活力增加、细胞凋亡减少以及 LDH 和 MDA 降低。此外，H/R 暴露后 miR-132 水平降低，而 NG-R1 处理后则升高。当 miR-132 过表达时，H/R 诱导的细胞损伤可得到恢复。下调 miR-132 则限制了 NG-R1 对 H/R 损伤的保护作用。我们还发现，HBEGF 是 miR-132 的直接靶标。H/R 损伤后 HBEGF 表达增加，而 NG-R1 处理后则逆转。
本研究表明，NG-R1 通过上调 miR-132 和下调其靶蛋白 HBEGF，显著保护 H9c2 细胞免受 H/R 诱导的损伤。
