SB203580 attenuates acute lung injury and inflammation in rats with acute pancreatitis in pregnancy
SB203580 attenuates acute lung injury and inflammation in rats with acute pancreatitis in pregnancy
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SB203580减轻妊娠期急性胰腺炎大鼠的急性肺损伤和炎症
DOI：
10.1007/s10787-018-0522-9
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发表时间：
2018-08
影响因子：
5.8
通讯作者：
Wang Weixing
中科院分区：
文献类型：
--
作者：
Zhou Yu;Xia Hongmiao;Zhao Liang;Mei Fangchao;Li Man;You Yundong;Zhao Kailiang;Wang Weixing
妊娠期急性胰腺炎（APIP）可导致母胎多脏器损伤，有丝分裂原活化蛋白激酶（MAPK）信号通路可能参与其中；然而，APIP是否会导致急性肺损伤以及P38MAPK信号通路是否参与其发病机制尚不清楚。本研究旨在探讨P38MAPK信号通路的参与以及P38MAPK抑制剂SB203580对APIP诱导的急性肺损伤的保护作用。将24只妊娠后期SD大鼠随机分为4组：假手术（SO）组、SB302580 （SB）组、APIP组和SB + APIP组。造模后6 h处死大鼠。通过血清淀粉酶（AMY）、脂肪酶（LIPA）及组织病理学改变评价胰腺炎的严重程度。采用H&E和免疫荧光法对肺组织和炎症细胞浸润进行组织学评估。测定肺湿/干（W/D）重量比，采用酶联免疫吸附试验（ELISA）检测肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-1β、IL-6水平。Western blot检测大鼠肺组织中磷酸化和总P38、肿瘤坏死因子(TNF)-α、细胞间粘附分子1 （ICAM-1）的蛋白表达。APIP诱导大鼠胰腺和肺部出现明显的病理改变，其病理评分明显高于对照组。结果显示，APIP大鼠肺组织中P38MAPK磷酸化水平升高。与APIP组相比，SB203580干预可减轻胰腺和肺的病理性损伤，降低血清AMY和LIPA，降低肺组织中TNF-α、IL-1β和IL-6的分泌，降低炎症细胞的浸润和肺W/D比，抑制P38MAPK信号通路的激活。这些结果表明，APIP可导致急性肺损伤和炎症，而SB203580可通过抑制P38MAPK信号通路和阻断炎症反应来抑制肺损伤。
Acute pancreatitis in pregnancy (APIP) can lead to multiple maternal and fetal organ injury and mitogen-activated protein kinase (MAPK) signaling pathway may be involved in it; however, whether APIP can result in acute lung injury and P38MAPK signaling pathway is involved in the pathogenesis has not been elucidated. The present study was undertaken to investigate the participation of P38MAPK signaling pathway and the protective effect of SB203580, an inhibitor of P38MAPK on acute lung injury induced by APIP. Twenty-four late-gestation SD rats were randomly assigned to four groups: Sham operation (SO) group, SB302580 (SB) group, APIP group, and SB + APIP group. All the rats were killed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY) and lipase (LIPA) and histopathological changes. Histological assessment of the lung and inflammatory cell infiltration was performed by H&E and immunofluorescence assay. The lung wet/dry (W/D) weight ratio was determined, and the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the protein expression of phosphorylated and total P38, tumor necrosis factor (TNF)-α, and intercellular adhesion molecules 1 (ICAM-1) in lung tissues. Obvious pathological changes existed in pancreas and lung after the induction of APIP, and their pathological scores were significantly higher than that of control group. The results showed that the phosphorylation of P38MAPK was elevated in the lung of APIP rats. Compared with APIP group, the intervention of SB203580 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated the secretion of TNF-α, IL-1β, and IL-6 in lung, reduced the inflammatory cells’ infiltration and lung W/D ratio and inhibited the activation of P38MAPK signaling pathway. These results suggest that APIP can lead to acute lung injury and inflammation and SB203580 can inhibit the lung injury by inhibiting the P38MAPK signaling pathway and blocking the inflammatory responses.
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DOI：
10.1007/978-3-030-26710-0_69
发表时间：
2020
期刊：
Evidence-Based Critical Care
影响因子：
--
作者：
M. Ragland;C. Weiss
通讯作者：
M. Ragland;C. Weiss
影响因子：
3.4
作者：
Zhou Y;Zhao L;Mei F;Hong Y;Xia H;Zuo T;Ding Y;Wang W
通讯作者：
Wang W
DOI：
10.1073/pnas.1514018113
发表时间：
2016-02
期刊：
Proceedings of the National Academy of Sciences
影响因子：
--
作者：
T. Roger;A. Schneider;M. Weier;F. Sweep;D. Le Roy;J. Bernhagen;T. Calandra;E. Giannoni
通讯作者：
T. Roger;A. Schneider;M. Weier;F. Sweep;D. Le Roy;J. Bernhagen;T. Calandra;E. Giannoni
影响因子：
3.1
作者：
R. Zou;Maohua Wang;Ye Chen;Xin Fan;Bo Yang;Juan Du;Xiao-bin Wang;Ke-xuan Liu;Jun Zhou
通讯作者：
R. Zou;Maohua Wang;Ye Chen;Xin Fan;Bo Yang;Juan Du;Xiao-bin Wang;Ke-xuan Liu;Jun Zhou
妊娠期急性胰腺炎大鼠模型胎肺损伤的初步研究
影响因子：
2.8
作者：
Zhao Liang;Zuo Teng;Shi Qiao;Mei Fang-chao;Hong Yu-pu;Deng Wen-Hong;Yu Jia;Hu Peng;Wang Wei-xing
通讯作者：
Wang Wei-xing