The role of tumor suppressor factor CYLD in lung injury associated with acute necrotizing pancreatitis
10.3760/cma.j.issn.1007-8118.2013.01.018
- VernacularTitle:肿瘤抑制蛋白CYLD在急性坏死性胰腺炎大鼠肺损伤中的作用
- Author:
Bei JIN
;
Limin LIU
;
Wenmao YAN
;
Shi CHENG
- Publication Type:Journal Article
- Keywords:
Pancreatitis,acute necrotizing;
Tumor suppressor proteins;
Lung;
Wounds and injuries
- From:
Chinese Journal of Hepatobiliary Surgery
2013;(1):58-61
- CountryChina
- Language:Chinese
-
Abstract:
Objective Acute necrotizing pancreatitis (ANP) may cause lung injury.This study explores two factors that are associated with lung damage from ANP,the expression of tumor suppressor factor CYLD and nuclear factor-kappa B (NF-κB).Methods 72 adult Sprague-Dawley rats were randomly divided into 3 groups:sham operation,ANP,and GdCl3 treatment groups (n=24 for each group).A retrograde injection of 5% sodium taurocholate into the biliopancreeatic duct of rats induced ANP,and the animals were killed 1,3,6,and 12 hours after the ANP induction.AMs were harvested by bronchoalveolar lavage technique,and TNF-a and IL-1β levels in bronchoalveolar lavage fluid (BALF) were evaluated.Lung tissue was checked with histological examinations,and the activity of NF-κB and CYLD in AM were measured by western blot.Results TNF-α and IL-1β secreted by AM were gradually elevated,peaked on the sixth hour,had maximums of (491.3 ±20.3)ng/L and (178.83±11.32)ng/L respectively,and decreased on the twelfth hour.The levels of TNF-α and IL-1β in the ANP group were significantly higher than the sham operation group (P<0.05),and the GdC13 group levels were obviously lower than ANP group.In the sham operation group,the expression of NF-κB was low and CYLD was high.In the ANP group,when compared to the sham operation group,the expression of NF-κB rose after 3 hours and continued to rise with time progression (P<0.05).In contrast,CYLD protein expression in the ANP group dropped after 3 hours and continued to gradually decrease (P<0.05).The CYLD and NF-κB protein expression in GdCl3 groups had similar trends as the ANP group.GdCl3 group CYLD levels began to rise at 6 hours (P<0.05),and NF κB levels began to fall at 1 hour (P<0.05).The expression of NF-κB and CYLD possessed a negative correlation in both the ANP and GdCl3 groups (r =-0.918,r=-0.723,P< 0.01).Conclusions Therefore,in acute lung injury associated with acute pancreatitis,CYLD expression decreased with evident phases,such as a decrease in levels after 3 hours,and NF κB expression increased.Also,GdCl3 may be responsible for upregulation of CYLD expression and downregulation of NF-κB expression,and confirmed that CYLD had a negative effect on NF-κB.Perhaps GdCl3 could be used in the future to ameliorate the lung injury associated with ANP.