Dexmedetomidine inhibits the release of inflammatory cytokines and exerts a systemic anti-inflammatory effect and has potential protective effects on vital organs such as lung, heart, and kidneys. The aim of this study was to investigate the effect of dexmedetomidine on LPS-treated HK-2 cells in vitro and explore the potential mechanisms. The HK-2 cells were pretreated with dexmedetomidine before LPS induction. CCK-8, flow cytometry, ELISA, or qRT-PCR was performed to detect cell proliferation, apoptosis, and proinflammatory cytokine expression. The levels of MALAT1 in HK-2 cells under different stimulation were measured by qRT-PCR. Then, m6A RNA immunoprecipitation was performed to detect methylated MALAT1 in HK-2 cells. The results showed dexmedetomidine suppressed cell viability, induced cell apoptosis, and reduced inflammation cytokine production of LPS-treated HK-2 cells. Besides, dexmedetomidine reduced the expression of MALAT1 in HK-2 cells under LPS stimulation. In addition, ALKBH5 could up-regulate MALAT1 expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. ALKBH5 knockdown inhibited cell viability, induced cell apoptosis, and decreased inflammation cytokine production of LPS-treated HK-2 cells. In short, dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which may provide potential targets for the prevention and treatment of sepsis-induced kidney injury.

右美托咪定抑制炎性细胞因子的释放，发挥全身抗炎作用，对肺、心、肾等重要器官具有潜在的保护作用。本研究的目的是在体外研究右美托咪定对 LPS 处理的 HK-2 细胞的影响并探索可能的机制。HK-2细胞在LPS诱导前用右美托咪定预处理。进行 CCK-8、流式细胞术、ELISA 或 qRT-PCR 以检测细胞增殖、凋亡和促炎细胞因子的表达。通过qRT-PCR测量不同刺激下HK-2细胞中MALAT1的水平。然后，进行 m6A RNA 免疫沉淀以检测 HK-2 细胞中的甲基化 MALAT1。结果显示右美托咪定抑制细胞活力，诱导细胞凋亡，并减少 LPS 处理的 HK-2 细胞的炎症细胞因子产生。此外，右美托咪定可降低 LPS 刺激下 HK-2 细胞中 MALAT1 的表达。此外，ALKBH5 可以通过去甲基化上调 MALAT1 的表达。此外，右美托咪定抑制 LPS 处理的 HK-2 细胞中 ALKBH5 的表达。ALKBH5 敲低抑制了 LPS 处理的 HK-2 细胞的细胞活力、诱导细胞凋亡和减少炎症细胞因子的产生。简而言之，右美托咪定通过抑制ALKBH5的表达来抑制LPS处理的HK-2细胞的生物学行为体外研究可能为脓毒症肾损伤的防治提供潜在靶点。