Effect of dexmedetomidine pretreatment on TLR4/NF-κB signaling pathway during intestinal ischemia-reperfusion in rats
10.3760/cma.j.issn.0254-1416.2019.01.008
- VernacularTitle:右美托咪定预先给药对大鼠肠缺血再灌注时TLR4/NF-κB信号通路的影响
- Author:
Jing YANG
1
;
Youping WU
;
Yan XU
;
Wenbin XI
;
Hui DENG
;
Chao FU
;
Weifeng TU
Author Information
1. 南方医科大学附属南部战区总医院麻醉科
- Keywords:
Dexmedetomidine;
Intestine;
Reperfusion injury;
Toll-like receptor 4;
NF-κB
- From:
Chinese Journal of Anesthesiology
2019;39(1):31-35
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of dexmedetomidine pretreatment on Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway during intestinal ischemia-reperfusion (I/R) in rats.Methods Twenty-four male Spragne-Dawley rats,weighing 180-220 g,were divided into 3 groups (n =8 each) using a random number table method:sham operation group (S group),intestinal I/R group (I group) and dexmedetomidine pretreatment group (DP group).Intestinal I/R model was established by occlusion of the superior mesenteric artery for 1 h followed by 2-h reperfusion in anesthetized rats.Dexmedetomidine 100 μg/kg was intraperitoneally injected at 30 min before ischemia in DP group.Blood samples were collected from hearts at the end of reperfusion for determination of the serum intestinal fatty acid binding protein (I-FABP) level by enzyme-linked immunosorbent assay.The intestinal tissues were obtained at the end of reperfusion for examination of pathologic changes and for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) contents (by enzyme-linked immunosorbent assay) and expression of TLR4,MyD88,phosphorylated NF-κB p65 (p-NF-κB p65) in total protein and NF-κB p65 in nucleoprotein (by Western blot).The degree of intestinal tissue damage was graded using Chiu's scoring system.Results Compared with S group,the Chiu's score and concentrations of IFABP in serum and contents of TNF-α and IL-1β in intestinal tissues were significantly increased,and the expression of TLR4,MyD88 and p-NF-κB p65 in total protein and NF-κB p65 in nucleoprotein was up-regulated in I/R group,and the Chiu's score was significantly increased,the expression of MyD88 and p-NF-κB p65 was up-regulated (P＜0.05),and no significant change was found in serum I-FABP concentration,contents of TNF-α and IL-1β,or expression of TLR4 in total protein and NF-κB p65 in nucleoprotein in DP group (P＞0.05).Compared with I/R group,the Chiu's score,serum I-FABP concentration,and contents of TNF-α and IL-1β were significantly decreased,and the expression of TLR4,MyD88 and p-NF-κB p65 in total protein and NF-κB p65 in nucleoprotein was down-regulated in DP group (P＜0.05).Conclusion The mechanism by which dexmedetomidine pretreatement mitigates intestinal I/R injury may be related to inhibiting activation of TLR4/NF-κB signaling pathway in rats.
