NF-κB-induced activation of NLRP3 inflammasome by LCN2 after intracerebral hemorrhage in rats
10.19845/j.cnki.zfysjjbzz.2023.0126
- VernacularTitle:大鼠脑出血后NF-κB诱导LCN2激活NLRP3炎症小体的研究
- Author:
Lin GAN
1
;
Peng YU
1
;
Ming DONG
1
Author Information
1. Department of Neurology and Neuroscience Center,The First Hospital of Jilin University,Changchun 130021,China
- Publication Type:Journal Article
- Keywords:
Intracerebral hemorrhage;
LCN2
- From:
Journal of Apoplexy and Nervous Diseases
2023;40(6):536-539
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of the elevated expression of LCN2 during intracerebral hemorrhage(ICH) and its involvement in inflammatory response after hemorrhage. Methods Male Sprague-Dawley rats were given an injection of autologous arterial blood(100 μl) at the basal ganglia,and the rats in the control group were given an injection of an equal volume of normal saline using the same surgical procedure. Ventricular injection of the NF-κB-specific inhibitors parthenolide and BAY11-7082 was performed for pretreatment,and after transfection with scrambled LCN2RNA or LCN2 siRNA,the levels of NLRP3,ASC,and cleaved caspase-1 were measured as the indicators for the status of inflammasome activation. Western blot,RT-PCR,and immunohistochemistry were used to measure the protein and mRNA expression levels of LCN2.Results Western blotting showed that there was a significant increase in the protein expression level of LCN2 in the ipsilateral basal ganglia on days 1,3,and 7 after hemorrhage and a significant reduction in this level on day 14.On day 3 after intracerebral hemorrhage,the protein expression level of LCN2 in the ipsilateral side was 71 times higher than that in the contralateral side(2.70±0.46 vs 0.04±0.01,P<0.001) and was 84 times higher than that in the control group(0.92±0.14 vs 0.01±0.01,P<0.001). Pretreatment with the NF-κB-specific inhibitors parthenolide and BAY11-7082 could inhibit the expression of LCN2.There were significant increases in the protein expression levels of NLRP3,ASC,and cleaved caspase-1 after transfection with scrambled siRNA,and LCN2 siRNA significantly reduced the expression of these inflammasome-associated proteins. Conclusion This study suggests that iron release after ICH can induce the expression of LCN2,and LCN 2 may play an important role in the inflammatory process after hemorrhage.
- Full text:2024061615591955212NF-κB-induced activation of NLRP3 inflammasome by LCN2 after intracerebral hemorrhage in rats.pdf