An enterogenic infection occurs when intestinal mucosal disruption is followed by the invasion of intestinal bacteria into the blood and distant organs, which can result in severe diseases or even death. Our previous study using Rhesus monkeys as an in vivo model revealed that methamphetamine (MA) induced intestinal mucosal barrier damage, which poses a high risk of enterogenic infection. However, how methamphetamine causes intestinal mucosal barrier damage remains largely unknown. In this study, we employed an in vitro model, and found that MA treatment could inhibit the expression of miR-181c, which directly targets and regulates TNF-α, and ultimately induces apoptosis and damages the intestinal barrier. Moreover, we measured TNF-α serum levels as well as the intestinal mucosal barrier damage indicators (diamine oxidase, d-lactic acid, and exotoxin) and found that their levels were significantly higher in MA-dependents than in healthy controls (P < 0.001). To the best of our knowledge, this is the first report evidencing that miR-181c is involved in MA-induced intestinal barrier injury via TNF-α regulation, which introduces novel potential therapeutic targets for MA-dependent intestinal diseases.

中文翻译：

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甲基苯丙胺诱导的肠黏膜屏障功能改变是通过 microRNA-181c/TNF-α/紧密连接轴发生的

肠源性感染发生在肠黏膜破裂后，肠道细菌侵入血液和远处器官，可导致严重疾病甚至死亡。我们之前使用恒河猴作为体内模型的研究表明，甲基苯丙胺 (MA) 会引起肠黏膜屏障损伤，这会造成肠源性感染的高风险。然而，甲基苯丙胺如何导致肠黏膜屏障损伤在很大程度上仍然未知。在本研究中，我们采用体外模型，发现 MA 治疗可以抑制 miR-181c 的表达，miR-181c 直接靶向和调节 TNF-α，最终诱导细胞凋亡并破坏肠道屏障。此外，我们测量了 TNF-α 血清水平以及肠粘膜屏障损伤指标（二胺氧化酶、d-乳酸、和外毒素），并发现 MA 依赖者的水平显着高于健康对照组（P < 0.001）。据我们所知，这是第一份证明 miR-181c 通过 TNF-α 调节参与 MA 诱导的肠道屏障损伤的报告，这为 MA 依赖性肠道疾病引入了新的潜在治疗靶点。