Curcumin Attenuates Pulmonary Inflammation in Lipopolysaccharide Induced Acute Lung Injury in Neonatal Rat Model by Activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) Pathway.
Curcumin Attenuates Pulmonary Inflammation in Lipopolysaccharide Induced Acute Lung Injury in Neonatal Rat Model by Activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) Pathway.
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DOI：
10.12659/msm.908714
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发表时间：
2018-02-26
期刊：
影响因子：
--
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Cheng K;Yang A;Hu X;Zhu D;Liu K
本研究旨在探讨姜黄素对内毒素(LPS)诱导的新生儿急性肺损伤(ALI)的治疗作用及其可能的分子机制。用脂多糖建立ALI新生动物模型。给动物注射姜黄素和/或过氧化物酶体增殖物激活受体γ(PPARγ)抑制剂BAGE(双酚A二缩水甘油醚)。通过测定PaO2和肺湿/干重比(W/D)评价肺水肿程度。用EMSA法测定PPARγ活性。采用双抗体夹心法检测大鼠肺泡灌洗液中高迁移率族蛋白1(HMGB1)、糖基化终产物分泌型受体(RAGE)、肿瘤坏死因子α(肿瘤坏死因子α)、白介素6(IL6)、转化生长因子β1(β1)水平。免疫印迹法检测肺组织中HMGB1、RAGE、血红素氧合酶1、肿瘤坏死因子α、白介素6和转化生长因子β1的表达水平。姜黄素可明显改善新生ALI大鼠的肺功能，提高PaO2，降低W/D。姜黄素可上调新生ALI大鼠肺组织PPARγ活性和HO1的表达水平，而肺组织PAR活性和HO1表达水平则受到抑制。姜黄素可显著降低新生ALI大鼠肺组织和肺泡灌洗液中HMGB1、RAGE、肿瘤坏死因子α、白介素6和转化生长因子β1的水平。PPARγ抑制剂BAGE给药不利于姜黄素减轻肺水肿、抑制炎性细胞因子的表达和恢复PPARγ/HO1信号的激活。姜黄素通过抑制PPAR、γ/HO1调节的HMGB1/RAGE促炎通路诱导的炎症反应，减轻内毒素诱导的ALI大鼠肺水肿。
This study aimed to investigate the therapeutic effect of curcumin in lipopolysaccharide (LPS) induced neonatal acute lung injury (ALI) and the possibly associated molecular mechanisms. ALI neonatal animal model was established by using LPS. Curcumin and/or peroxisome proliferator-activated receptor γ (PPARγ) inhibitor BADGE (bisphenol A diglycidyl ether) were administrated to animals. Lung edema was evaluated by PaO2 and lung wet/dry weight ratio (W/D) measurements. EMSA was used to determine the PPARγ activity. Levels of high-mobility group box 1 (HMGB1), secretory receptor for advanced glycation end products (RAGE), tumor necrosis factor α (TNFα), interleukin 6 (IL6), and transforming growth factor β1 (TGFβ1) in bronchoalveolar lavage fluid (BALF) were examined by ELISA. Western blotting was used to evaluate the expression levels of HMGB1, RAGE, heme oxygenase 1 (HO1), TNFα, IL6, and TGFβ1 in lung tissue. Curcumin administration significantly improved lung function by increasing PaO2 and decreasing W/D in neonatal ALI rats. Curcumin treatment upregulated the PPARγ activity and expression level of HO1 which were suppressed in lung tissue of neonatal ALI rats. Elevated levels of HMGB1, RAGE, TNFα, IL6, and TGFβ1 in both lung tissue and BALF from neonatal ALI rats were decreased dramatically by curcumin treatment. PPARγ inhibitor BADGE administration impaired curcumin’s alleviation on lung edema, inhibitory effects on inflammatory cytokine expression and recovery of PPARγ/HO1 signaling activation. Curcumin alleviated lung edema in LPS-induced ALI by inhibiting inflammation which was induced by PPARγ/HO1 regulated-HMGB1/RAGE pro-inflammatory pathway.
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