| 崔栋然,范方雪,武琼,等.艾司氯胺酮对脂多糖诱导的心肌细胞内质网应激与细胞凋亡的影响[J].安徽医药,2026,30(3):486-491. |
| 艾司氯胺酮对脂多糖诱导的心肌细胞内质网应激与细胞凋亡的影响 |
| Effect esketamine on lipopolysaccharide-induced endoplasmic reticulum stress and apoptosis in cardiomyocytes |
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| DOI：10.3969/j.issn.1009-6469.2026.03.012 |
| 中文关键词: 艾司氯胺酮 肌细胞，心脏 细胞损伤 凋亡 内质网应激 脂多糖 |
| 英文关键词: Esketamine Myocytes, cardiac Cell injury Apoptosis Endoplasmic reticulum stress Lipopolysaccharide |
| 基金项目:河北省医学科学研究课题计划( 20210040)；邯郸市科学技术研究与发展计划项目( 22422083044ZC) |
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| 中文摘要: |
| 目的观察艾司氯胺酮对脂多糖诱导的心肌细胞内质网应激( ERS)与细胞凋亡的影响。方法 2022年 1—12月，采用脂多糖处理的 H9c2细胞为心肌细胞毒模型，将细胞分为空白组(正常培养，不进行任何处理)、模型组( 1 mg/L脂多糖处理 H9c2细胞)及艾司氯胺酮组( 8 mg/L艾司氯胺酮和 1 mg/L脂多糖共同处理 H9c2细胞)。处理 24 h后，检测并比较各组 H9c2细胞凋亡数量，细胞内凋亡蛋白胱天蛋白酶 3(caspase-3)、胱天蛋白酶 12(caspase-12)及多腺苷二磷酸核糖聚合酶 1(PARP1)细胞内活性氧、丙二醛、超氧化物歧化酶( SOD)活性，培养上清中肿瘤坏死因子 α(TNF-α)、白细胞介素( IL)-6和 IL-1β蛋白水平，及细胞内 TNF-α、IL-6、IL-1β mRNA水平。检测并比较各组细胞 ERS相关分子钙连蛋白、葡萄糖调节蛋白 78(GRP78)、 C/EBP同源蛋白( CHOP)、磷酸化蛋白激酶 R样内质网激酶( p-PERK)、磷酸化真核翻译起始因子 2α(p-eIF2α)蛋白水平。结果空白组、模型组及艾司氯胺酮组细胞晚期凋亡率分别为( 1.88±0.17)%、(14.03±1.92)%、(5.68±1.43)%，钙连蛋白水平(荧光强度)分别为 25.10±5.72、582.71±43.03、107.11±19.89。与空白组相比，模型组细胞凋亡细胞数量，活化 PARP1/PARP1、活化 caspase-3/ caspase-3及活化 caspase-12/caspase-12，细胞内活性氧、丙二醛及 TNF-α、IL-6、IL-1β的 mRNA水平，细胞培养上清 TNF-α、IL-6、 IL-1β蛋白水平，细胞内钙连蛋白、 GRP78、CHOP蛋白水平， p-PERK、p-eIF2α蛋白水平显著增加( P<0.05)，而艾司氯胺酮组上述指标水平显著低于模型组(P<0.05)。同时模型组 SOD活性显著低于空白组(P<0.05)，而艾司氯胺酮组 SOD活性显著高于模型组( P<0.05)，但低于空白组( P<0.05)。结论在 H9c2细胞中，艾司氯胺酮能够抑制细胞凋亡，改善脂多糖诱导的 ERS及炎症反应，这可能对减轻心肌细胞损伤有所帮助。 |
| 英文摘要: |
| Objective To investigate the effects of esketamine on endoplasmic reticulum stress (ERS) and apoptosis induced by lipo.polysaccharide (LPS) in cardiomyocytes.Methods From January to December 2022, an LPS-treated H9c2 cell model of cardiomyo.cyte injury was used. Cells were divided into three groups: a control group (normal culture without intervention), a model group (treatedwith 1 mg/L LPS), and an esketamine group (co-treated with 8 mg/L esketamine and 1 mg/L LPS). After 24 hours of treatment, the fol.lowing parameters were measured and compared among groups: apoptotic cell count; intracellular levels of apoptotic proteins and theiractivated forms, including caspase-3, caspase-12, and poly (ADP-ribose) polymerase 1 (PARP1); intracellular levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) activity; protein levels of tumor necrosis factor-α (TNF-α), in. terleukin-6 (IL-6), and interleukin-1β (IL-1β) in the culture supernatant; and intracellular mRNA levels of TNF-α, IL-6, and IL-1β. Additionally, protein levels of ERS-related molecules-calreticulin, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), phosphorylated protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphorylated eukaryotic initiation factor 2α (eIF2α)-were assessed.Results The late apoptosis rates in the control, model, and esketamine groups were (1.88±0.17)%, (14.03±1.92)% , and (5.68±1.43)% , respectively. Calreticulin levels (fluorescence intensity) were 25.10±5.72, 582.71±43.03, and 107.11±19.89, respectively. Compared with the control group, the model group showed significant increases in apoptotic cell count; the ratios ofactivated to total PARP1, caspase-3, and caspase-12; intracellular levels of ROS and MDA; mRNA levels of TNF-α, IL-6, and IL-1β; supernatant protein levels of TNF-α, IL-6, and IL-1β; and intracellular protein levels of calreticulin, GRP78, CHOP, p-PERK, and p-eIF2α (all P<0.05). In the esketamine group, these indicators were significantly lower than those in the model group (P<0.05). Mean. while, SOD activity in the model group was significantly lower than that in the control group (P<0.05), whereas it was significantly high. er in the esketamine group than in the model group (P<0.05), but lower than that in the control group (P<0.05).Conclusion Esket. amine inhibits apoptosis, ameliorates LPS-induced ERS, and suppresses inflammatory responses in H9c2 cells, suggesting a potentialprotective effect against cardiomyocyte injury. |
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