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Title: [Dexmedetomidine preconditioning alleviates acute lung injury induced by intestinal ischemia-reperfusion in rats by inhibiting NLRP3 inflammasome activation].
Author: Han B, Chen M, Yang C, Li X.
Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2021 Dec 20; 41(12):1857-1863. PubMed ID: 35012919.
Abstract:
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (P < 0.05) with also significantly increased expressions of NLRP3, ASC, and caspase-1 proteins (P < 0.05) but obviously lowered expression of p-AMPK protein (P < 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 (P < 0.05), and significant lower expressions of NLRP3, ASC, and caspase-1 (P < 0.05) but higher expression of p-AMPK protein (P < 0.05). CONCLUSION: 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. 目的: 探讨右美托咪定（Dex）对大鼠肠缺血再灌注（II/R）所致急性肺损伤（ALI）的保护作用以及核苷酸结合域样受体蛋白3（NLRP3）炎性小体活性的影响。方法: 将32只健康雄性SD大鼠，随机分为4组（8只/组）。假手术组（Sham组）仅暴露肠系膜上动脉（SMA），肠缺血再灌注组（II/R组）阻断SMA 1 h后再灌注2 h，II/R+右美托咪定处理组（Dex+II/R组）右美托咪定干预后行再灌注，Dex假手术组（Dex组）右美托咪定预处理假手术组。Sham组和II/R组腹腔注射等量生理盐水。采取夹闭SMA 1 h再灌注2 h的方法建立肠缺血再灌注损伤模型。测定各组大鼠肺部组织湿/干质量比值（W/D）、髓过氧化物酶（MPO）活性，HE染色评估肺组织病理学变化以及行肺损伤评分；ELISA检测肺部组织中炎性因子TNF-α、IL-18、IL-1β水平；Western blot检测肺部组织中NLRP3、凋亡相关斑点样蛋白（ASC）、Caspase-1及磷酸化腺苷酸活化蛋白激酶（p-AMPK）蛋白的表达水平。结果: 相较于Sham组，II/R组肺组织病理损伤明显，W/D值、MPO活性及肺组织中的TNF-α、IL-18、IL-1β表达显著升高（P < 0.05），肺组织中NLRP3、ASC、Caspase-1蛋白表达增加（P < 0.05），p-AMPK蛋白表达减少（P < 0.05）；相较于II/R组，Dex+II/R组肺组织病理损伤轻微，W/D值、MPO活性及肺组织中的TNF-α、IL-18、IL-1β表达明显下降（P < 0.05），肺组织NLRP3、ASC、Caspase-1蛋白表达明显下降（P < 0.05），p-AMPK蛋白表达明显增加（P < 0.05）。结论: 右托美咪定通过对NLRP3炎性小体激活的抑制，减轻炎性反应，进而改善大鼠II/R所致的ALI。

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