Department of Intensive Care Unit, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Can Respir J. 2022 Jul 31;2022:8433960. doi: 10.1155/2022/8433960. eCollection 2022.
Dexmedetomidine (DEX), which is reported to be a newly discovered, novel -2 adrenoceptor agonist, is known to exhibit anti-inflammatory properties in several diseases. DEX regulates inflammation-related signaling pathways and genes through interactions with several miRNAs. This study verified that expression levels of miR-140-3p were diminished when alveolar type II cells were exposed to LPS. However, the levels of miR-140-3p were confirmed as showing an increase with DEX treatment. These observations revealed that the expression of miR-140-3p was related to the beneficial effects that accompanied the DEX treatment of LPS-induced ALI. In addition, PD-1/PD-L1 expression increased extensively when RLE-6TN cells were induced by LPS. The increased expression was reduced after treatment with DEX. Thus, it appears that the PD-L1 expression was targeted directly by miR-140-3p, resulting in the partial repression of PD-L1 levels, which involved the inhibition of p-JNK and Bnip3 expression. Therefore, DEX was shown to inhibit the PD-L1 expression by promoting partially increased miR-140-3p levels in RLE-6TN cells. DEX also inactivated the JNK-Bnip3 pathway, resulting in the inhibition of inflammation and alleviating alveolar type II cell injury.
右美托咪定（DEX）是一种新发现的新型 2 肾上腺素能受体激动剂，已知其在多种疾病中具有抗炎作用。DEX 通过与多种 miRNAs 的相互作用来调节与炎症相关的信号通路和基因。本研究验证了当肺泡 II 型细胞暴露于 LPS 时，miR-140-3p 的表达水平降低。然而，DEX 处理后 miR-140-3p 的水平被证实增加。这些观察结果表明，miR-140-3p 的表达与 DEX 治疗 LPS 诱导的 ALI 伴随的有益效果有关。此外，当 RLE-6TN 细胞被 LPS 诱导时，PD-1/PD-L1 的表达广泛增加。用 DEX 处理后，表达增加减少。因此，PD-L1 的表达似乎被 miR-140-3p 直接靶向，导致 PD-L1 水平的部分抑制，涉及 p-JNK 和 Bnip3 表达的抑制。因此，DEX 通过促进 RLE-6TN 细胞中 miR-140-3p 水平的部分增加来抑制 PD-L1 的表达。DEX 还使 JNK-Bnip3 通路失活，从而抑制炎症并减轻肺泡 II 型细胞损伤。
