Qu Yan, Xiong Wei, Zhou Rui, Song Ning, Qian Jinqiao
Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Mol Med Rep. 2025 Sep;32(3). doi: 10.3892/mmr.2025.13616. Epub 2025 Jul 11.
Dexmedetomidine (Dex) is a selective α2‑adrenergic receptor agonist used for its sedative effects in anesthesia and critical care. Although Dex exhibits cardioprotective effects, to the best of our knowledge, the mechanisms underlying these effects, particularly in a high‑glucose (HG) environment, remain unclear. Research into the role of Dex in alleviating oxidative stress injury in cardiac myoblasts through the PI3K/AKT signaling pathway may reveal novel cardioprotective mechanisms, enhance the understanding of cell survival and metabolic regulation, and offer potential clinical applications in cardiac surgery and critical care. The aim of the present study was to assess the protective effect and mechanism of Dex preconditioning (DP) against hydrogen peroxide (HO)‑induced H9C2 cardiac myoblast injury under HG conditions. H9C2 cardiac myoblasts were either untreated or pretreated with 10 nM Dex and the PI3K inhibitor LY294002 before exposure to HO to induce oxidative cellular damage in the presence of HG culture medium. Cell viability assays were carried out, and apoptosis was evaluated using flow cytometry, TUNEL assays and western blotting. Additionally, the relative levels of oxidative stress indicators, including superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA), were determined. Exposure to HO significantly decreased cell viability and increased apoptosis in H9C2 cardiac myoblasts cultured in HG conditions. Treatment with Dex significantly mitigated HO‑induced apoptosis, as evidenced by reduced expression of caspase‑3 and BAX, and increased levels of BCL‑2. In addition, oxidative stress was elevated in the HG + HO group, as indicated by increased levels of the oxidative stress marker MDA, and reduced levels of the antioxidant enzymes SOD and CAT compared with those in the HG group. By contrast, DP in the DP + HG + HO group reduced MDA levels, and increased SOD and CAT levels, indicating improved oxidative stress regulation. Treatment with the PI3K/AKT inhibitor LY294002 in the LY294002 + HG + DP + HO group prevented these effects, further increasing MDA levels, and decreasing SOD and CAT levels compared with the DP + HG + HO group, suggesting that the protective effects of Dex were abrogated by inhibition of the PI3K/AKT pathway. The present study revealed that Dex pretreatment attenuated H9C2 cardiac myoblast injury via the PI3K/AKT signaling pathway under HG conditions. Its protective effects may be achieved by reducing oxidative stress damage to cardiac myoblasts.
右美托咪定（Dex）是一种选择性α2-肾上腺素能受体激动剂，因其在麻醉和重症监护中的镇静作用而被使用。尽管Dex具有心脏保护作用，但据我们所知，这些作用的潜在机制，尤其是在高糖（HG）环境下，仍不清楚。研究Dex通过PI3K/AKT信号通路减轻心肌成纤维细胞氧化应激损伤的作用，可能揭示新的心脏保护机制，增进对细胞存活和代谢调节的理解，并为心脏手术和重症监护提供潜在的临床应用。本研究的目的是评估Dex预处理（DP）对HG条件下过氧化氢（HO）诱导的H9C2心肌成纤维细胞损伤的保护作用及机制。在HG培养基存在下，将H9C2心肌成纤维细胞不做处理或用10 nM Dex和PI3K抑制剂LY294002预处理，然后暴露于HO以诱导细胞氧化损伤。进行细胞活力测定，并使用流式细胞术、TUNEL测定和蛋白质印迹法评估细胞凋亡。此外，还测定了氧化应激指标的相对水平，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和丙二醛（MDA）。在HG条件下培养的H9C2心肌成纤维细胞中，暴露于HO显著降低了细胞活力并增加了细胞凋亡。Dex处理显著减轻了HO诱导的细胞凋亡，这表现为caspase-3和BAX表达降低以及BCL-2水平升高。此外，与HG组相比，HG + HO组的氧化应激升高，表现为氧化应激标志物MDA水平升高以及抗氧化酶SOD和CAT水平降低。相比之下，DP + HG + HO组中的DP降低了MDA水平，并提高了SOD和CAT水平，表明氧化应激调节得到改善。LY294002 + HG + DP + HO组中用PI3K/AKT抑制剂LY294002处理阻止了这些作用，与DP + HG + HO组相比，进一步提高了MDA水平，并降低了SOD和CAT水平，这表明抑制PI3K/AKT通路消除了Dex的保护作用。本研究表明，在HG条件下，Dex预处理通过PI3K/AKT信号通路减轻了H9C2心肌成纤维细胞损伤。其保护作用可能是通过减少对心肌成纤维细胞的氧化应激损伤来实现的。
