B Han1, M Chen1, C Yang1, X Li1. 1. Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
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.
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.
Authors: Lakshmi Kannan; Katalin Kis-Toth; Kazuhisa Yoshiya; To-Ha Thai; Seema Sehrawat; Tanya N Mayadas; Jurandir J Dalle Lucca; George C Tsokos Journal: Proc Natl Acad Sci U S A Date: 2013-08-13 Impact factor: 11.205