Faculty of Anesthesiology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, China.
Department of Anesthesiology, Urumqi General Hospital of Lanzhou Military Command, Urumqi 830000, China.
Int Immunopharmacol. 2020 Mar;80:106150. doi: 10.1016/j.intimp.2019.106150. Epub 2020 Jan 17.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infections. Previous studies have indicated that lidocaine, an amide local anesthetic, has anti-inflammatory properties; however, the underlying mechanism remains unclear. In this study, we have shown that lidocaine dose-dependently inhibits lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages and that lidocaine protects mice from LPS-induced inflammation. Moreover, we have demonstrated that lidocaine reduces the release of TNF-α and IL-6 through the reduction of the expression of GLUT1 and HK2 to further suppress HIF1α-induced aggravation of inflammatory cascades. Lidocaine can inhibit the enhanced glycolysis and glycolytic capacity induced by LPS in the macrophages. As an inhibitor of PHDs (prolyl hydroxylases), Dimethyloxalylglycine (DMOG) can reduce the anti-inflammatory effects of lidocaine. In conclusion, the present study indicates that lidocaine can be used as a potential therapeutic agent for sepsis.
脓毒症是一种危及生命的器官功能障碍，由宿主对感染的失调反应引起。先前的研究表明，酰胺类局部麻醉药利多卡因具有抗炎特性；然而，其潜在机制尚不清楚。在本研究中，我们表明利多卡因能够剂量依赖性地抑制巨噬细胞中脂多糖（LPS）诱导的肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的产生，并且利多卡因可以保护小鼠免受 LPS 诱导的炎症。此外，我们还证明，利多卡因通过降低 GLUT1 和 HK2 的表达来减少 TNF-α和 IL-6 的释放，从而进一步抑制 HIF1α 诱导的炎症级联反应的加重。利多卡因可以抑制 LPS 诱导的巨噬细胞中增强的糖酵解和糖酵解能力。作为脯氨酰羟化酶（PHD）的抑制剂，二甲基草酰甘氨酸（DMOG）可以降低利多卡因的抗炎作用。总之，本研究表明利多卡因可用作脓毒症的潜在治疗剂。
