Expression of toll-like receptor 4/NF-κB signaling pathway in acute necrotizing pancreatitis-associated lung injury and intervention of lipoxin A4 analogue
10.3760/cma.j.issn.1671-0282.2019.10.014
- VernacularTitle: Toll样受体4/NF-κB信号通路在急性重症胰腺炎相关肺损伤中的表达及脂氧素A4类似物的干预作用研究
- Author:
Liming WANG
1
;
Zequn NIU
;
Jiangli SUN
;
Hui FENG
;
Honghong PEI
;
Longfei PAN
Author Information
1. Emergency Department, Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, China
- Publication Type:Journal Article
- Keywords:
TLR4;
Lipoxin A4;
Acute necrotizing pancreatitis;
Acute lung injury
- From:
Chinese Journal of Emergency Medicine
2019;28(10):1251-1256
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of toll-like receptor 4 (TLR4)/NF-κB signaling pathway in acute necrotizing pancreatitis (ANP)-associated lung injury and the intervention of lipoxin A4 (LXA4) analogue.
Methods:Forty-five Sprague-Dawley rats were randomly(random number)divided into the sham operation group, experimental group, and intervention group, each group containing 15 rats. ANP animal models were prepared by injecting sodium taurocholate into biliopancreatic tube in the experimental group. No sodium taurocholate was injected into biliopancreatic duct in the sham operation group. After the preparation of ANP animal models in the intervention group, LXA4 was injected through the tail vein. Rats in each group were randomly divided into 3 subgroups (n=5 each subgroup). The serum amylase, TNF- α, IL-1β, IL-6 and endotoxin levels were detected 6, 12 and 24 h after the operation. The lung injury scores were assessed and the lung wet/dry weight ratio was calculated. The expressions of TLR4 and NF-κB p65 in lung tissues were detected by Western blot.
Results:Serum levels of amylase, TNF-α, IL-1β, IL-6 and endotoxin in the experimental and intervention groups were significantly higher than those in the sham operation group, while the levels of the above indicators in the intervention group was significantly lower than those in the experimental group, and the differences were statistically significant (P<0.05). Postoperative lung injury scores and lung wet/dry weight ratio in the experimental group were significantly higher than those in the sham operation group, and the differences were statistically significant (P<0.05). Lung injury scores in the intervention group 6 h after operation had no significant difference compared with those in the sham operation group (P>0.05), while lung wet/dry weight ratio in the intervention group 6 h after operation, and lung injury scores and lung wet/dry weight ratio in the intervention group 12 h or 24 h respectively after operation were significantly higher than those in the sham operation group, with statistically significant differences (P<0.05). Postoperative lung injury scores and lung wet/dry weight ratio in the intervention group were significantly lower than those in the experimental group, and the differences were statistically significant (P<0.05). The expressions of TLR4 and p65 in the lung tissues of the experimental and intervention groups were significantly higher than those of the sham operation group, and the expressions of TLR4 and p65 in the lung tissues of the intervention group were significantly lower than those of the experimental group, with statistically significant differences (P<0.05).
Conclusions:LXA4 can reduce the severity of acute necrotizing pancreatitis-associated lung injury, and its mechanism is related to reducing the stimulation of endotoxin, thus inhibiting TLR4 signaling pathway and the activation of p65 to down-regulate the level of pro-inflammatory cytokines.
