Role of inhibitor of nuclear factor kappa B kinase alpha on renal inflammation after ischemia-reperfusion injury and its associated mechanism
10.3760/cma.j.issn.1001-7097.2013.09.006
- VernacularTitle:核因子κB抑制物激酶α在肾脏缺血再灌注损伤炎性反应中的作用及机制
- Author:
Qian ZHANG
;
Xin WAN
;
Lin LIU
;
Xin CHEN
;
Wenjuan HUANG
;
Wen CHEN
;
Changchun CAO
- Publication Type:Journal Article
- Keywords:
Reperfusion injury;
Inflammation;
Acute renal injury;
IKKα
- From:
Chinese Journal of Nephrology
2013;29(9):670-675
- CountryChina
- Language:Chinese
-
Abstract:
Objective To reveal the role of inhibitor of nuclear factor kappa B kinase alpha (IKKα) in renal inflammation after renal ischemia-reperfusion (IR) injury and its potential associated mechanism.Methods Ischemia-reperfusion injury models were induced in a total of 24 healthy C57BL/6 male mice.Renal function and histological changes were estimated.The expression and site of IKKα,p52,RelB,IL-10 and IL-18 were determined by immunohistochemistry and Western blotting.After the short hairpin RNA(shRNA)targeting IKKα was injected into renal parenchyma,renal function and protein expressions of IKKα,p52,RelB,IL-10,IL-18 were detected.Results Compared with sham-operated group[Scr(7.30±0.13) μmol/L,BUN (8.39± 0.30) mmol/L],levels of Scr [(29.80± 2.10)μmol/L,(27.00±3.40) μmol/L,(23.00±3.70) μmol/L] and BUN [(9.47±3.50) mmol/L,(11.68 ±4.30)mmol/L,(13.12±2.10) mmol/L] were higher on day 1,3,7 and the injury of kidney was serious in IR injury group.Immunohistochemical expression of both IL-18 and IL-10 were increased.Markedly increased IKKα,p52 and RelB protein expression were noted in experiments from day 1 to day 7 during kidney recovery period,with a peak on day 3 and then decreasing toward baseline after day 7.Compared with IR injury group,low-expression of IKKα by injection of shRNA up-regulated the expression of IL-18 and down-regulated the expression of IKKα,p52,RelB and IL-10.Conclusions The NF-κB pathway is activated and IKKα expression is up-regulated during the kidney ischemiareperfusion injury,low-expression of IKKα may block inflammation resolution via down-regulation of alternative NF-κB pathway family members of both p52 and RelB.
