Effect of dexmedetomidine on expression of hypoxia-inducible factor-1α during endotoxin-caused apoptosis in macrophages of mice
10.3760/cma.j.issn.0254-1416.2018.12.026
- VernacularTitle:右美托咪定对内毒素致小鼠巨噬细胞凋亡时HIF-1α表达的影响
- Author:
Xing MAO
1
;
Hongguang CHEN
;
Mengying YAN
;
Jingcheng FENG
;
Guolin WANG
;
Keliang XIE
;
Yonghao YU
Author Information
1. 300052,天津医科大学总医院麻醉科 天津市麻醉学研究所
- Keywords:
Dexmedetomidine;
Sepsis;
Apoptosis;
Macrophage;
Mitochondria;
Apoptosis;
Hypoxia-induced factor 1,αlpha subunit
- From:
Chinese Journal of Anesthesiology
2018;38(12):1505-1508
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of dexmedetomidine on expression of hypoxia-inducible factor-1α (HIF-1α) during endotoxin-caused apoptosis in macrophages of mice.Methods Mouse macrophage cell line RAW264.7 cultured in vitro were seeded in 6-well or 96-well plates and divided into 4 groups (n=16 each) when cell confluence reached 60％-70％ using a random number table method:control group (group Con),dexmedetomidine group (group Dex),lipopolysaccharide (LPS) group,and LPS plus dexmedetomidine group (group LPS+Dex).Phosphate buffer solution was added in group Con.Dexmedetomidine 1 μmol/L was added in group Dex.LPS 1 μg/ml was added in LPS and LPS+Dex groups.Dexmedetomidine 1 μmol/L was added immediately after adding LPS in group LPS+Dex.Cells were then cultured for 24 h in each group.Cell apoptosis was measured using TUNEL,mitochondrial membrane potential using JC-1,reactive oxygen species (ROS) content by ROS kit,and ATP content by ATP kit.The apoptosis rate was calculated.The expression of HIF-1α,cytochrome C (Cyt-c),caspase-9 and cleaved caspase-3 was detected by Western blot.Results Compared with group Con,the apoptosis rate and ROS content were significantly increased,ATP content and mitochondrial membrane potential were decreased,the expression of HIF-1α,Cyt-c,caspase-9 and cleaved caspase-3 was up-regulated in group LPS (P＜ 0.05),and no significant change was found in the parameters mentioned above in group Dex (P＞0.05).Compared with group LPS,the apoptosis rate and ROS content were significantly decreased,ATP content and mitochondrial membrane potential were increased,the expression of HIF-1α was up-regulated,and the expression of Cyt-c,caspase-9 and cleaved caspase-3 was down-regulated in group LPS + Dex (P＜0.05).Conclusion Dexmedetomidine can reduce endotoxin-caused oxidative stress injury to macrophages,improve mitochondrial function and inhibit mitochondrial apoptosis,and the mechanism may be related to upregulating the expression of HIF-1α in mice.
