Casticin Alleviates Acute Lung Injury in Septic Mice by Regulating Endoplasmic Reticulum Stress
10.3870/j.issn.1672-0741.24.09.014
- VernacularTitle:紫花牡荆素通过调控内质网应激减轻脓毒症小鼠急性肺损伤
- Author:
Zhijie YAN
1
;
Yan YOU
Author Information
1. 南昌大学第四附属医院重症医学科,南昌 330003
- Publication Type:Journal Article
- Keywords:
sepsis;
acute lung injury;
casticin;
Ca2+influx;
endoplasmic reticulum stress
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):477-482
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of casticin on acute lung injury(ALI)in sepsis mice,and explore its mecha-nism.Methods Sixty C57BL/6 mice were randomly divided into sham operation group,model group,low(2.5 mg/kg),medium(5 mg/kg),and high-dose(10 mg/kg)of casticin groups,with 12 mice in each group.Except for the sham operation group,the mice in the other groups were used to establish sepsis models using cecal ligation and puncture(CLP)method.After successful model construction,the mice were continuously administered for 2 days.Blood gas analyzer was used to detect arterial partial pressure of oxygen(PaO2)and arterial partial pressure of CO2(PaCO2)in mice.The lower lobe of right lung was isolated and the ratio of wet to dry weight was measured.HE staining was used to observe the pathologicalchanges in lung tissue.ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in alveolar lavage fluid(BALF).Fluo-4/AM fluorescence probe labeling method was used to detect intracellular Ca2+concentration in lung tissuecells.Western blot was used to detect the protein expression levels of calcium channel regulatory protein 1(Orai1),CCAAT/enhancer binding protein homologous protein(CHOP)and glucose regulatory protein 78(GRP78)in lung tissue.Results Compared with the sham surgery group,mice in model group showed a significant decrease in PaO2(P<0.05),while PaCO2 and lung tissue wet to dry weight ratio significantly increased(all P<0.05).Thelung tissuestructurewas disrupted,with thickening of alveolar walls,col-lapse of alveoli,interstitial edema,and inflammatory cell infiltration.Levels of TNF-α,IL-1βand IL-6 in BALF were significantly increased in lung tissue(all P<0.05).The intracellular Ca2+concentration in lung tissue cells and the protein expression levels of Orai1,CHOP,and GRP78 in lung tissue werealso significantly increased(all P<0.05).Compared with the model group,the PaO2 of mice in each dose of casticin group increased(all P<0.05),and PaCO2 and lung tissue wet to dry weight ratio decreased significantly(all P<0.05).The pathological damage to lung tissue was alleviated,and the levels of TNF-α,IL-1β and IL-6 in BALF were significantly reduced(all P<0.05).The intracellular Ca2+concentration in lung tissue cells and the protein expres-sion levels of Orai1,CHOP and GRP78 in lung tissuewerealso significantly reduced(all P<0.05).Effects of high-dose casticin on various indicators were more significant than that of low-dose casticin(all P<0.05).Conclusion Casticin can improve ALI and inhibit inflammatory responsein sepsis mice,and its mechanism may be related to Ca2+influx inhibition and endoplasmic re-ticulum stress alleviation.
