Role of ROS/Nrf2 signaling pathway in desflurane preconditioning-induced reduction of lipopolysaccharide-induced acute cerebral inflammation in rats
10.3760/cma.j.cn131073.20191116.00625
- VernacularTitle:ROS/Nrf2信号通路在地氟烷预处理减轻脂多糖诱导大鼠脑急性炎症中的作用
- Author:
Haiyan XUE
1
;
Zhaokai ZENG
;
Guozhong CHEN
;
Liping WANG
Author Information
1. 福建医科大学福总临床医学院 联勤保障部队第九〇〇医院 厦门大学附属东方医院 福建中医药大学福总教学医院 蚌埠医学院福总教学医院麻醉与围术期医学科，福州 350025
- From:
Chinese Journal of Anesthesiology
2020;40(6):741-746
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of reactive oxygen species (ROS) /nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in desflurane preconditioning-induced reduction of lipopolysaccharide (LPS)-induced acute cerebral inflammation in rats.Methods:One hundred and twenty clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=30 each) using a random number table method: control group (group C), LPS-induced acute cerebral inflammation group (group L), desflurane preconditioning group (group D), and N-acetylcysteine plus desflurane preconditioning group (group ND). LPS 1 mg/kg was injected via the tail vein to establish the model of acute cerebral inflammation in L, D and ND groups.In group D, rats inhaled 8.2% desflurane for 1 h once a day for 5 consecutive days, and LPS was intravenously injected at 24 h after the end of the 5th inhalation.In group ND, ROS scavenger N-acetylcysteine 150 mg/kg was intraperitonealy injected at 30 min before each inhalation of desflurane, and the other treatments were similar to those previously described in group D. The expression of Nrf2 and kelch-like ECH-associated protein 1 (Keap1) in microglia and astrocytes in the hippocampal CA1 region was determined by immunofluorescence double staining before LPS injection (at 24 h after the last desflurane preconditioning). Morris water maze test was used to measure the escape latency, space exploration time spent in the original platform quadrant, and frequency of crossing the original platform at 6, 12 and 24 h after injecting LPS.The expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, interleukin-18 (IL-18) and interleukin-1beta (IL-1β) in microglia and astrocytes in the hippocampal CA1 region was determined by immunofluorescence double staining at 6, 12 and 24 h after injecting LPS.Nissl staining and immunofluorescence were used to count normal neurons and activated microglia and astrocytes in the hippocampus at 24 h after LPS injection. Results:Compared with group C, no significant change was found in the expression of Nrf2 and Keap1 in microglia and astrocytes before LPS injection ( P>0.05), and the escape latency was significantly prolonged, the space exploration time spent in the original platform quadrant was shortened, the frequency of crossing the original platform was decreased, the number of normal neurons was decreased, the number of activated microglia and astrocytes was increased, and the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was up-regulated after injecting LPS in group L ( P<0.05). Compared with group L, the expression of Nrf2 was significantly up-regulated, and the expression of Keap1 was down-regulated before injecting LPS ( P<0.05), and the escape latency was shortened, the space exploration time spent in the original platform quadrant was prolonged, the frequency of crossing the original platform was increased, the number of normal neurons was increased, the number of activated microglia and astrocytes was reduced, and the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was down-regulated after injecting LPS in group D( P<0.05). Compared with group D, the expression of Nrf2 was significantly down-regulated, the expression of Keap1 was up-regulated before injecting LPS ( P<0.05), and the escape latency was significantly prolonged, the space exploration time spent in the original platform quadrant was shortened, the frequency of crossing the original platform was decreased, the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was up-regulated, the number of normal neurons was reduced, and the number of activated microglia and astrocytes was increased after LPS injection in group ND ( P<0.05). Conclusion:ROS/Nrf2 signaling pathway is involved in desflurane preconditioning-induced reduction of LPS-induced acute cerebral inflammation in rats.
