Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.
Department of Biomedical Engineering, College of Precision Instruments and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China.
Oxid Med Cell Longev. 2023 Jan 7;2023:1464853. doi: 10.1155/2023/1464853. eCollection 2023.
Endotoxemia (ET) is a common critical illness in patients receiving intensive care and is associated with high mortality and prolonged hospital stay. The intestinal epithelial cell dysfunction is regarded as the "engine" of deteriorated ET. Although electroacupuncture (EA) can mitigate endotoxin-induced intestinal epithelial cell dysfunction in ET, the mechanism through which EA improves endotoxin-induced intestinal injury for preventing ET deterioration needs further investigation.
An in vivo ET model was developed by injecting lipopolysaccharide (LPS) in wild-type and PINK1-knockout mice. An in vitro model was also established by incubating epithelial cells in the serum samples obtained from both groups of mice. Hemin and zinc protoporphyrin IX (ZnPP) were applied to activate or inhibit heme oxygenase 1 (HO-1) production. EA treatment was performed for 30 min consecutively for 5 days before LPS injection, and on the day of the experiment, EA was performed throughout the process. Samples were harvested at 6 h after LPS induction for analyzing tissue injury, oxidative stress, ATP production, activity of diamine oxidase (DAO), and changes in the levels of HO-1, PTEN-induced putative kinase 1 (PINK1), mitochondrial fusion and fission marker gene, caspase-1, and interleukin 1 beta (IL-1).
In the wild-type models (both in vivo and vitro), EA alleviated LPS-induced intestinal injury and mitochondrial dysfunction, as indicated by decreased reactive oxygen species (ROS) production and oxygen consumption rate (OCR) and reduced levels of mitochondrial fission proteins. EA treatment also boosted histopathological morphology, ATP levels, DAO activity, and levels of mitochondrial fusion proteins in vivo and vitro. The effect of EA was enhanced by hemin but suppressed by Znpp. However, EA + AP, Znpp, or hemin had no effects on the LPS-induced, PINK1-knocked out mouse models.
EA may improve the HO-1/PINK1 pathway-mediated mitochondrial dynamic balance to protect the intestinal barrier in patients with ET.
内毒素血症（ET）是重症监护患者中常见的危重病，与高死亡率和住院时间延长有关。肠上皮细胞功能障碍被认为是 ET 恶化的“引擎”。虽然电针（EA）可以减轻 ET 中内毒素诱导的肠上皮细胞功能障碍，但 EA 改善内毒素诱导的肠损伤以防止 ET 恶化的机制仍需进一步研究。
通过注射脂多糖（LPS）在野生型和 PINK1 敲除小鼠中建立体内 ET 模型。还通过孵育来自两组小鼠的血清样本在体外建立上皮细胞模型。血红素和锌原卟啉 IX（ZnPP）用于激活或抑制血红素加氧酶 1（HO-1）的产生。在 LPS 注射前连续 5 天每天进行 30 分钟的 EA 治疗，在实验当天，整个过程中进行 EA 治疗。在 LPS 诱导后 6 小时采集样本，分析组织损伤、氧化应激、ATP 产生、二胺氧化酶（DAO）活性以及 HO-1、PTEN 诱导的假定激酶 1（PINK1）、线粒体融合和分裂标记基因、半胱天冬酶-1 和白细胞介素 1β（IL-1β）水平的变化。
在野生型模型中（体内和体外），EA 减轻了 LPS 诱导的肠道损伤和线粒体功能障碍，表现为活性氧（ROS）产生和耗氧量（OCR）减少，线粒体分裂蛋白水平降低。EA 治疗还增强了体内和体外的组织病理学形态、ATP 水平、DAO 活性和线粒体融合蛋白水平。血红素增强了 EA 的作用，但 ZnPP 抑制了 EA 的作用。然而，EA+AP、ZnPP 或血红素对 LPS 诱导的 PINK1 敲除小鼠模型没有影响。
EA 可能通过改善 HO-1/PINK1 通路介导的线粒体动态平衡来保护 ET 患者的肠道屏障。
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