Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine, Dentistry, Pharmaceutical Sciences, 2-5-1, Shikatacho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
Department of Anesthesiology and Resuscitology, Okayama University Medical School, 2-5-1, Shikatacho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
Sci Rep. 2023 Mar 16;13(1):4374. doi: 10.1038/s41598-023-31483-1.
Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation.
右美托咪定（DEX）可通过抑制炎症减轻失血性休克（HS）复苏（HSR）模型大鼠的肺损伤。在这里，我们旨在研究 DEX 的这些作用是否归因于自噬激活。因此，我们建立了 HSR 大鼠模型，并将其分为四组。通过抽血来诱导 HS。然后，通过重新注入抽出的血液和生理盐水来复苏大鼠。复苏后 24 小时处死大鼠。采集肺组织进行组织病理学检查、湿/干肺重比测定和自噬相关标志物蛋白 LC3、P62、Beclin-1 和 ATG12-ATG5 缀合物水平的检测。肺组织苏木精-伊红染色的形态学发现和肺湿/干重比表明，HSR+DEX 大鼠的肺损伤得到改善。然而，自噬抑制剂氯喹（CQ）消除了这种作用。检测自噬相关蛋白的浓度表明，DEX 给药增加了 LC3、ATG12-ATG5 和 Beclin-1 的表达，降低了 P62 的表达。CQ+DEX 给药后，这些蛋白的表达水平与 HSR 组相似。总之，DEX 在 HSR 模型中诱导自噬激活。这些发现表明，DEX 给药通过自噬激活部分改善了 HSR 诱导的肺损伤。
