Inhibition of macrophage migration inhibitory factor attenuates inflammation and fetal kidney injury in a rat model of acute pancreatitis in pregnancy
Inhibition of macrophage migration inhibitory factor attenuates inflammation and fetal kidney injury in a rat model of acute pancreatitis in pregnancy
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DOI：
10.1016/j.intimp.2018.12.068
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Wang, Wei-xing
中科院分区：
文献类型：
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作者：
Li, Man;Yu, Jia;Wang, Wei-xing
妊娠期急性胰腺炎（APIP）是妊娠期的一种严重疾病，多发生在妊娠晚期。它可能导致其他并发症，包括早产和高胎儿死亡率。在本研究中，我们在大鼠模型中研究了巨噬细胞迁移抑制因子（MIF）抑制剂（S，R）-3-（4-羟基苯基）-4，5二氢-5-异恶唑乙酸甲酯（ISO-1）对母体急性坏死性胰腺炎（ANP）相关胎儿肾损伤的保护作用及其潜在机制。采用牛磺胆酸钠盐水溶液逆行胆胰管灌注建立APIP大鼠模型。模型诱导前30 min腹腔注射ISO-1。测量母体血清淀粉酶、脂肪酶、肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-1β的水平。评估母体胰腺及胎儿肾损伤情况，检测胎儿肾脏中MIF、磷酸化p38MAPK（p-p38）、核因子κB（NF-κB）、TNF-α、IL-1β的表达情况。结果显示，胎鼠在APIP期间表现出明显的急性肾损伤，而用ISO-1预处理的孕鼠则显着减轻了病变。 ISO-1 还显着降低了 MIF 的表达以及 p38MAPK、NF-κ B 的激活以及 TNF-α 和 IL-1 beta 的水平。这些结果表明，ISO-1 可以通过抑制 MIF 介导的 p38MAPK/NF-kappa B 信号通路来减轻炎症反应，从而减轻 ANP 妊娠大鼠的胎儿肾损伤。
Acute pancreatitis in pregnancy (APIP) is a severe disease during pregnancy that mostly occurs during the third trimester. It can lead to additional complications including preterm delivery and high fetal mortality. In this study, we investigated the protective effects of (S, R)-3-(4-hydroxyphenyl)-4, 5dihydro-5-isoxazole acetic methyl ester (ISO-1), an inhibitor of macrophage migration inhibitory factor (MIF), on fetal kidney injury associated with the maternal acute necrotizing pancreatitis (ANP) and its potential mechanisms in a rat model. The APIP rat model was induced by retrograde infusion of sodium taurocholate saline solution into biliopancreatic duct. ISO-1 was given by intraperitoneally injection 30 min before the model was induced. The levels of maternal serum amylase, lipase, tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL)-1 beta were measured. Maternal pancreas and fetal kidney injury were evaluated, and the expressions of MIF, phospho-p38MAPK (p-p38), nuclear factor-kappa B (NF-kappa B), TNF-alpha, IL-1 beta in fetal kidneys were detected. The results showed that fetal rats exhibited obvious acute kidney injury during APIP, and pregnant rats pretreated with ISO-1 notably attenuated the lesions. ISO-1 also significantly reduced the expression of MIF and the activations of p38MAPK, NF-kappa B, as well as the levels of TNF-alpha and IL-1 beta. These results indicated that ISO-1 could attenuate fetal kidney injury in pregnant rats with ANP by inhibiting MIF mediated p38MAPK/NF-kappa B signal pathways to reduce inflammatory response.