The mechanism by which oxidative stress in bovine fatty liver activates the NLRP3 inflammasome to induce hepatocyte pyroptosis
10.16303/j.cnki.1005-4545.2025.11.23
- VernacularTitle:奶牛脂肪肝氧化应激激活NLRP3炎性小体引发肝细胞焦亡的机制
- Author:
Jie XU
1
;
Kangfeng JIANG
1
;
Yuan HU
1
;
Kui WANG
1
;
Yiyi ZHAO
1
;
Yan TIAN
1
;
Xinyuan ZHANG
1
;
Binghai PAN
1
;
Qingqing ZHOU
1
;
Xiaobing LI
1
Author Information
1. 云南农业大学动物医学院,云南 昆明 650201
- Publication Type:Journal Article
- Keywords:
dairy cattle;
fatty liver;
oxidative stress;
NLRP3 inflammasomes;
pyroptosis
- From:
Chinese Journal of Veterinary Science
2025;45(11):2481-2489
- CountryChina
- Language:Chinese
-
Abstract:
Fatty liver is common disease of nutritional metabolism in the perinatal period,character-ized by elevated levels of NEFA in the blood and disorders of lipid metabolism.High concentra-tions of NEFA damage mitochondria and promote the release of reactive oxygen species(ROS).At the same time,lipid peroxidation occurs in lipid accumulation in hepatocytes,producing free radi-cals such as ROS,which leads to oxidative stress in the liver.When the level of intracellular ROS increases,thioredoxin-interacting protein(TXNIP)activates nucleotide-binding oligomerization structure-like protein 3(NLRP3)inflammasomes,and oxidative stress can regulate pyroptosis,but it is unclear whether reactive oxygen species(ROS)produced by oxidative stress in hepatocytes can mediate pyroptosis and induce liver injury in dairy cows through the TXNIP/NLRP3 pathway.In this study,liver tissue samples from healthy dairy cows and fatty liver cows were collected,and NEFA was used to construct a fatty liver cell model,and triglyceride(TG)content and oxidative stress related indicators were detected by kit.Western blot was used to detect the activation of NL-RP3 inflammasomes,the inflammatory pathway of NF-κB and the expression levels of pyroptosis-related proteins.Fluorescence quantitative PCR was used to detect the relative expression level of inflammatory factor mRNA.The results showed that compared with the healthy(control)group,the TG content of fatty liver tissue and fatty liver cells was significantly increased(P＜0.05),the activities of SOD and GSH-Px were significantly decreased(P＜0.05),and the protein expression levels of TXNIP,NLRP3,GSDMD-N and Caspase-1 were significantly up-regulated(P＜0.05).The results of the antioxidant model of fatty hepatocytes using NEFA and antioxidants(NAC)showed that compared with the fatty hepatocyte model,the content of ROS in hepatocytes was sig-nificantly reduced,and oxidative stress,NLRP3 inflammasome activation and pyroptosis were alle-viated.In summary,this study found that when fatty liver disease occurs in dairy cows,ROS pro-duced by oxidative stress in the liver can mediate pyroptosis through the TXNIP/NLRP3 path-way,which can lead to liver injury in fatty liver cows.
