Han B, Chen M, Yang C, Li X
Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Dec 20;41(12):1857-1863. doi: 10.12122/j.issn.1673-4254.2021.12.15.
To investigate the protective effect of dexmedetomidine (Dex) against acute lung injury induced by intestinal ischemia-reperfusion (II/R) in rats and its effect on NLRP3 inflammasome activity.
Thirty-two normal male SD rats were randomly divided into 4 groups (n=8): the sham operation group, where the superior mesenteric artery (SMA) was exposed only; II/R group, where the SMA was occluded for 1 h followed by reperfusion for 2 h; Dex+II/R group, where the rats were subjected to II/R and received intraperitoneal injection of Dex before reperfusion; and Dex group, where the rats received Dex pretreatment and sham operation. The rats in sham operation group and II/R group received intraperitoneal injection of normal saline. The wet/dry weight ratio (W/D) and myeloperoxidase (MPO) activity in the lung tissues were measured, and HE staining was used to evaluate lung pathologies and determine lung injury score of the rats. The levels of inflammatory cytokines (TNF-α, IL-18, and IL-1β) in the lung tissue were detected using ELISA, and the expressions of NLRP3, ASC, caspase-1 and p-AMPK proteins were determined with Western blotting.
Compared with the sham-operated rats, the rats with II/R injury showed obvious lung pathologies and significantly increased W/D value, MPO activity and expression of TNF-α, IL-18 and IL-1β in the lung tissue ( < 0.05) with also significantly increased expressions of NLRP3, ASC, and caspase-1 proteins ( < 0.05) but obviously lowered expression of p-AMPK protein ( < 0.05) in the lung tissues. Compared with those in II/R group, the rats in Dex+II/R group showed milder lung pathologies, significantly reduced W/D value, MPO activity and expressions of TNF-α, IL-18 and IL-1β in the lung tissue ( < 0.05), and significant lower expressions of NLRP3, ASC, and caspase-1 ( < 0.05) but higher expression of p-AMPK protein ( < 0.05).
Dex treatment reduces II/R-induced inflammatory response by inhibiting the activation of NLRP3 inflammasomes, thereby improving acute lung injury caused by II/R in rats.
探讨右美托咪定（Dex）对大鼠肠缺血再灌注（II/R）诱导的急性肺损伤的保护作用及其对NLRP3炎性小体活性的影响。
将32只正常雄性SD大鼠随机分为4组（n = 8）：假手术组，仅暴露肠系膜上动脉（SMA）；II/R组，SMA阻断1小时后再灌注2小时；Dex + II/R组，大鼠进行II/R并在再灌注前腹腔注射Dex；Dex组，大鼠接受Dex预处理并进行假手术。假手术组和II/R组大鼠腹腔注射生理盐水。测定肺组织的湿/干重比（W/D）和髓过氧化物酶（MPO）活性，采用HE染色评估肺病理学并确定大鼠的肺损伤评分。使用ELISA检测肺组织中炎性细胞因子（TNF-α、IL-18和IL-1β）的水平，用蛋白质印迹法测定NLRP3、ASC、caspase-1和p-AMPK蛋白的表达。
与假手术大鼠相比，II/R损伤大鼠表现出明显的肺病理学改变，肺组织中W/D值、MPO活性以及TNF-α、IL-18和IL-1β的表达显著增加（P < 0.05），肺组织中NLRP3、ASC和caspase-1蛋白的表达也显著增加（P < 0.05），但p-AMPK蛋白的表达明显降低（P < 0.05）。与II/R组相比，Dex + II/R组大鼠的肺病理学改变较轻，肺组织中W/D值、MPO活性以及TNF-α、IL-18和IL-1β的表达显著降低（P < 0.05），NLRP3、ASC和caspase-1的表达显著降低（P < 0.05），但p-AMPK蛋白的表达较高（P < 0.05）。
Dex治疗通过抑制NLRP3炎性小体的激活减轻II/R诱导的炎症反应，从而改善大鼠II/R引起的急性肺损伤。
