The effect of irisin in alleviating mitochondrial damage and oxidative stress in the liver of mice with acute necrotizing pancreatitis
10.3760/cma.j.cn115667-20240726-00129
- VernacularTitle:鸢尾素缓解急性坏死性胰腺炎小鼠肝脏线粒体损伤及氧化应激的作用
- Author:
Jie LI
1
;
Yifan REN
;
Zhanli WEI
;
Yunjie DING
;
Xiaopeng LI
Author Information
1. 西安交通大学第二附属医院超声医学科,西安 710004
- Publication Type:Journal Article
- Keywords:
Acute necrotizing pancreatitis;
Liver injury;
Integrin;
Irisin;
Mitochondrion;
Oxidative stress;
Mouse
- From:
Chinese Journal of Pancreatology
2025;25(4):289-293
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the protective effect and mechanism of irisin on liver injury and mitochondrial dysfunction of hepatocytes in mice with acute necrotizing pancreatitis (ANP).Methods:24 mice were randomly divided into the control group, the ANP group, the irisin group and the cilengitide group, with 6 mice in each group. The ANP group was prepared by intraperitoneal injection of 20% L-arginine. The irisin group was injected with 250 μg/kg of irisin intraperitoneally on the basis of the induction of ANP. The cilengitide group was injected with the integrin receptor αVβ3/5 inhibitor cilengitide at 20 mg/kg on the basis of the treatment of the irisin group. The control group was injected with 0.9% normal saline instead of L-arginine. Routine liver histopathological examination and scoring were performed; immunohistochemical staining was used to detect the level of neutrophil infiltration in liver tissue; the ultrastructure changes of mitochondria were observed under transmission electron microscopy; biochemistry was used to detect the ATP content in liver tissue to reflect the changes in mitochondrial function; the total antioxidant capacity of liver tissue was detected by the ferric reducing/antioxidant power (FRAP) method; the DHE fluorescence probe labeling method was used to detect the accumulation degree of oxygen free radicals in liver tissue.Results:The livers of the control group showed no obvious abnormalities. However, the ANP group, the irisin group and the cilengitide group all had liver tissue damage and infiltration of inflammatory cells in the mice. Compared with the ANP group, the liver pathological score, the number of neutrophil infiltration, and the DHE fluorescence staining density in the irisin group were significantly lower [(3.40±0.72) vs (7.26±1.01) points, (14.67±2.51) vs (33.33±3.51) cells, (16.33±5.03) vs (50.33±10.69) cells], while the above indicators in the cilengitide group were all increased [(7.06±1.55) points, (40.33±5.03) cells, (51.00±12.8) cells]; the ATP content [(296.04±64.6), (54.77±18.05), (109.50±56.61), (40.29±11.68) μmol/gprot], and the antioxidant capacity [(0.19±0.01), (0.10±0.01), (0.17±0.02), (0.11±0.01) mmol/g] in the control group, ANP group, irisin group and cilengitide group changed accordingly. The above differences were statistically significant (all P value <0.05). Transmission electron microscopy observation revealed that the abnormal mitophagy of liver cells in the irisin group restored to normal, while the mitophagy abnormality in the cilengitide group was exacerbated. Conclusions:Irisin could improve the disordered mitochondrial function and oxidative stress in liver cells by acting on integrin receptors αVβ3/5, thereby alleviating liver damage and inflammatory responses in ANP mice.