Role of Notch pathway in Toll-like receptor 4 mediated inflammatory re-sponse in renal ischemia reperfusion injury in rats
10.3969/j.issn.1000-4718.2016.03.016
- VernacularTitle:Notch 通路在大鼠肾脏缺血再灌注损伤TLR4介导的炎症反应中的作用
- Author:
Xiaochang XU
;
Ye ZHU
;
Huitao ZHANG
;
Pingzhen CHEN
;
Jing ZHENG
;
Ning JIA
;
Yujing LIN
;
Lingling LI
;
Hua ZHANG
- Publication Type:Journal Article
- Keywords:
Kidney;
Ischemia-reperfusion injury;
Notch pathway;
Toll-like receptor 4;
Inflammation
- From:
Chinese Journal of Pathophysiology
2016;32(3):485-491
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the role of the Notch pathway in Toll-like receptor 4 ( TLR4 )-mediated in-flammatory response in renal ischemia reperfusion injury ( IRI) in rats.METHODS: A total of 75 male sprague-Dawley rats were randomly divided into sham operation group , IRI group and DAPT treatment group .Blood samples and the kid-neys were obtained at 6 h, 12 h, 24 h, 48 h and 72 h after reperfusion .The concentrations of blood urea nitrogen ( BUN) and serum creatinine (Scr) were measured.The serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were detected by ELISA, and the expression of Notch1, TLR4 and NF-κB p65 in the renal tissues was assessed by im-munohistochemistry and Western blot .RESULTS: The serum levels of BUN, Scr, TNF-αand IL-6 in IRI group were markedly increased as compared with sham group (P<0.05).The protein levels of Notch1, TLR4 and NF-κB p65 in re-nal tubular epithelial cells in IRI group was significantly enhanced as compared with sham group ( P<0.05 ) .In DAPT group, the serum levels of BUN, Scr, TNF-αand IL-6 were significantly reduced compared with IRI group (P<0.05), and the protein levels of Notch1, TLR4 and NF-κB p65 were apparently less than those in IRI group (P<0.05).CON-CLUSION:Significant changes of renal function , a rise of serum inflammatory factor including TNF-αand IL-6 and en-hanced expression of Notch 1, TLR4 and NF-κB p65 in the renal tissue occurred in the rats with IRI .γ-Secretase inhibitor DAPT attenuates TLR4-mediated inflammatory response in the renal IRI through the inhibition of Notch 1 and down-regula-tion of NF-κB.
