Effect of sodium sivelestat on expression of SPMs synthesis enzymes in mice with lipopolysaccharide-induced acute lung injury
10.3760/cma.j.cn131073.20240415.01120
- VernacularTitle:西维来司他钠对小鼠内毒素性急性肺损伤时SPMs合成酶表达的影响
- Author:
Chuanning LIU
1
;
Jia SHI
;
Yuhang LI
;
Meiling PIAO
;
Huayang LIU
;
Qiujia LI
;
Jianbo YU
Author Information
1. 天津医科大学附属南开医院麻醉与重症医学科,天津 300100
- Keywords:
Proteinase inhibitory proteins, secretory;
Endotoxins;
Acute lung injury;
Inflammation
- From:
Chinese Journal of Anesthesiology
2024;44(11):1386-1390
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of sodium sivelestat on the expression of specialized pro-resolving mediators (SPMs) synthesis enzymes in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=6 each) using a random number table method: control group (C group), LPS-induced ALI group (ALI group), and LPS-induced ALI + sodium sivelestat group (ALI+ SV group). ALI was induced by intravenous injection of LPS 15 mg/kg through the tail vein. Sodium sivelestat 50 mg/kg was intraperitoneally injected at 1 h after LPS administration. At 12 h after LPS administration, blood samples were collected from the eyeballs for routine blood tests, and the remaining blood was processed for serum extraction. The mice were sacrificed after anesthesia, and lung tissues were collected to determine the wet/dry weight (W/D) ratio, serum concentrations of interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay), expression of neutrophil elastase (NE) and SPMs synthesis enzymes 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX), and 15-lipoxygenase (15-LOX) in lung tissues (by Western blot) and to examine the pathological changes of lung tissues which were scored. Results:Compared with C group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β and IL-10 concentrations were significantly increased, the expression of NE was up-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was down-regulated in ALI group ( P<0.05). Compared with ALI group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β concentration were significantly decreased, the serum IL-10 concentration was increased, the expression of NE was down-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was up-regulated in ALI+ SV group ( P<0.05). Conclusions:The mechanism by which sodium sivelestat alleviates LPS-induced ALI may be related to up-regulating the expression of SPMs synthesis enzyme and promoting the resolution of pulmonary inflammation in mice.