Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy.
Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy.
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DOI：
10.3892/mmr.2018.8672
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发表时间：
2018-05
影响因子：
3.4
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Zhou Y;Zhao L;Mei F;Hong Y;Xia H;Zuo T;Ding Y;Wang W
巨噬细胞移动抑制因子（Macrophage migration inhibitory factor，MIF）是一种炎症细胞因子，参与多种急慢性炎症性疾病的发生发展。然而，其在妊娠急性胰腺炎（APIP）相关急性肺损伤中的作用尚未阐明。本研究旨在探讨MIF拮抗剂（S，R）3-（4-羟基苯基）-4，5-二氢-5-异恶唑乙酸甲酯（ISO-1）对急性肺损伤大鼠肺损伤的影响及其可能机制。18只孕晚期SD大鼠随机分为假手术组（SO）、APIP组和ISO-1组。造模后6 h处死大鼠。检测血清淀粉酶（AMY）、脂肪酶（利帕）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6水平，并进行组织病理学评分。肺损伤通过进行组织学和炎性细胞浸润调查来确定。Western blot检测肺组织中MIF、磷酸化P38、总P38和核因子-κB（NF-κB）蛋白的表达。结果表明，MIF在APIP大鼠肺组织中表达上调。与APIP组相比，ISO-1干预组胰腺和肺组织病理损伤减轻，血清AMY和利帕水平降低，血清TNF-α、IL-1β和IL-6水平降低，肺组织MPO阳性细胞数减少，P38 MAPK和NF-κB B的活化受到抑制。提示MIF在APIP诱导的肺损伤中被激活。本研究结果提示，MIF拮抗剂ISO-1对肺损伤和炎症具有保护作用，其机制可能与抑制P38 MAPK和NF-κB信号通路有关。
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in many acute and chronic inflammatory diseases. However, its role in acute lung injury associated with acute pancreatitis in pregnancy (APIP) has not yet been elucidated. The present study was undertaken to clarify the effect and potential mechanism of MIF antagonist (S,R)3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) in the development of acute lung injury in rats with APIP. Eighteen late-gestation SD rats were randomly assigned to three groups: Sham operation (SO) group, APIP group, and ISO-1 group. All the rats were sacrificed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY), lipase (LIPA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 and assessing the histopathological score. Lung injury was determined by performing histology and inflammatory cell infiltration investigations. Western blot analysis was used to detect the protein expression of MIF, phosphorylated and total P38 and nuclear factor-κB (NF-κB) protein in lungs. The results showed that MIF was upregulated in the lung of APIP rats. Compared with APIP group, the intervention of ISO-1 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated serum concentrations of TNF-α, IL-1β, and IL-6, reduced the number of MPO-positive cells in the lung and inhibited the activation of P38MAPK and NF-κB. These results suggest that MIF is activated in lung injury induced by APIP. Furhtermore, the present findings indicate that the MIF antagonist ISO-1 has a protective effect on lung injury and inflammation, which may be associated with deactivating the P38MAPK and NF-κB signaling pathway.
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