Relationship between Wnt/β-catenin signaling pathway and autophagy during hyperoxia-induced acute lung injury in infantile rats
10.3760/cma.j.cn131073.20230420.01016
- VernacularTitle:高氧诱发幼鼠急性肺损伤时Wnt/β-catenin信号通路与自噬的关系
- Author:
Jine JIA
1
;
Jianbo WANG
;
Zhiqiang YU
Author Information
1. 天津市中心妇产科医院麻醉科，天津 300052
- Keywords:
Oxygen;
Acute lung injury;
Wnt proteins;
β-catenin;
Autophagy
- From:
Chinese Journal of Anesthesiology
2023;43(10):1232-1236
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the relationship between Wnt/β-catenin signaling pathway and autophagy during hyperoxia-induced acute lung injury in infantile rats.Methods:A total of 24 clean-stage healthy male infantile Sprague-Dawley rats, aged 14 days, weighing 40-50 g, were allocated into 4 groups ( n=6 each) using a random number table method: control group (C group), hyperoxic acute lung injury (HALI) group, HALI+ IWP-2 group (HI group) and HALI+ DMF group (HD group). HALI model was developed by inhaling oxygen at a concentration greater than 90% for 72 h. Starting from 30 min before developing the model, IWP-2 15 mg/kg was intraperitoneally injected every day for 3 consecutive days in HI group, the equal volume of DMF solution was injected every day for 3 consecutive days in HD group, and the equal volume of normal saline was intraperitoneally injected instead in C and HALI groups. Blood samples were taken from the common carotid artery for blood gas analysis at the end of developing the model, and oxygenation index (OI) was calculated. Then the infantile rats were sacrificed under deep anesthesia, and lungs were removed for examination of the pathological changes which were scored and for determination of the weight to dry weight ratio (W/D ratio), contents of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and expression of Wnt3a, β-catenin, microtubule-associated protein 1 light chain 3(LC3), Beclin1 and p62 (by Western blot). LC3Ⅱ/LC3Ⅰ ratio was calculated. Results:Compared with C group, the OI was significantly decreased, the W/D ratio, lung injury score and contents of IL-6, IL-1β and TNF-α were increased, and the expression of Wnt3a, β-catenin and Beclin1 was up-regulated, the expression of p62 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in HALI, HD and HI groups ( P<0.05). Compared with HALI group, the OI was significantly decreased, the W/D ratio, lung injury score and contents of IL-6, IL-1β and TNF-α were increased, and the expression of Wnt3a, β-catenin and p62 was down-regulated, the expression of Beclin1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in HI group ( P<0.05), and no significant change was found in the parameters mentioned above in HD group ( P>0.05). Compared with HI group, the OI was significantly increased, the W/D ratio, lung injury score and contents of IL-6, IL-1β and TNF-α were decreased, and the expression of Wnt3a, β-catenin and p62 was up-regulated, the expression of Beclin1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in HD group ( P<0.05). Conclusions:In the pathophysiology of hyperoxia-induced acute lung injury in infantile rats, Wnt/β-catenin signaling pathway may be a negative regulator of autophagy. Wnt/β-catenin signaling pathway may be involved in the process of HALI through negative regulation of autophagy.
