糖皮质激素对高氧诱导新生大鼠肺组织RAGE-NF-&kappa;B通路的影响

胡剑; 俞敏; 唐云; 田兆方

doi:10.7499/j.issn.1008-8830.2015.01.018

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中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (1) : 81-85. DOI: 10.7499/j.issn.1008-8830.2015.01.018

论著·实验研究

糖皮质激素对高氧诱导新生大鼠肺组织RAGE-NF-κB通路的影响

胡剑, 俞敏, 唐云, 田兆方

作者信息 +

Effects of glucocorticoid on RAGE-NF-κB pathway in hyperoxia-induced lung tissues of neonatal rats

HU Jian, YU Min, TANG Yun, TIAN Zhao-Fang

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文章历史 +

摘要

目的探讨RAGE-NF-κB 信号通路在新生大鼠高氧肺损伤过程中的变化,以及糖皮质激素对其的影响.方法 24 只新生大鼠随机分为空气对照组、高氧模型组和激素干预组.模型组新生大鼠于生后即暴露于95% 氧气浓度环境中1 周,空气对照组大鼠生后仅暴露于同室内空气中饲养7 d,激素干预组于造模后行尾静脉注射地塞米松(1 mg/kg),隔天1 次,共3 次.日龄13 d 时处死全部大鼠,RT-PCR 检测各组肺组织RAGEmRNA 及NF-κB mRNA的表达;Western blot检测RAGE 及NF-κB 蛋白水平;ELISA 法检测血清及肺泡灌洗液(BALF)中TNF-α 和sRAGE 含量;苏木精- 伊红染色后行肺组织病理学评估.结果与对照组和激素干预组相比,高氧模型组肺组织RAGE、NF-κB 的mRNA 和蛋白表达水平均明显增高(均P<0.05),血清中sRAGE 含量明显升高(P<0.01),BALF 中sRAGE 含量下降(P<0.01);与对照组相比,激素干预组肺组织RAGE、NF-κB 的mRNA和蛋白表达水平明显升高(P<0.05),血清中sRAGE 含量明显升高(P<0.05),而BALF 中sRAGE 含量明显下降(P<0.05).结论 RAGE-NF-κB 通路在高氧诱导的新生大鼠肺损伤中活化增强,糖皮质激素可能通过下调RAGE-NF-κB 信号通路对高氧肺损伤发挥保护作用.

Abstract

Objective To explore the change of RAGE-NF-κB signaling pathway during the course of hyperoxiainduced lung injury in newborn rats, and the effect of glucocorticoid on this pathway. Methods Twenty-four Sprague- Dawley neonatal rats were randomly divided into three groups (n=8 each): sham control (control group), hyperoxiainduced acute lung injury (model group) and glucocorticoid-treated acute lung injury (glucocorticoid group). Rats were sacrificed at 13 days after birth. RAGE and NF-κB expression levels in lung tissues were detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factor α (TNF-α) and sRAGE in bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. Lung damage was evaluated by histological examinations. Results RAGE and NF-κB mRNA and protein expression levels in lung tissues were significantly increased in the model and glucocorticoid groups compared with the control group (P<0.05). Serum RAGE concentrations were significantly increased but RAGE concentrations in BALF were significantly reduced in the model and glucocorticoid groups compared with the control group (P<0.05). RAGE and NF-κB expression at both mRNA and protein levels in lung tissues was significantly lower in the glucocorticoid group than in the model group (P<0.05). RAGE concentrations were significantly lower in serum (P<0.05), but were higher in BALF (P<0.05) in the glucocorticoid group than in the model group. Conclusions RAGE-NF-κB pathway plays an important role in hyperoxia-induced lung injury in neonatal rats, and glucocorticoid administration may play a protective role against the lung injury by down-regulating RAGE-NF-κB signaling pathway.

导出引用

胡剑, 俞敏, 唐云, 田兆方. 糖皮质激素对高氧诱导新生大鼠肺组织RAGE-NF-κB通路的影响[J]. 中国当代儿科杂志. 2015, 17(1): 81-85 https://doi.org/10.7499/j.issn.1008-8830.2015.01.018

HU Jian, YU Min, TANG Yun, TIAN Zhao-Fang. Effects of glucocorticoid on RAGE-NF-κB pathway in hyperoxia-induced lung tissues of neonatal rats[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(1): 81-85 https://doi.org/10.7499/j.issn.1008-8830.2015.01.018

参考文献

[1] 侯伟, 刘海燕, 李丹, 等. 新生大鼠高氧肺损伤血管内皮生长因子蛋白及其mRNA 表达变化研究[J]. 中国当代儿科杂志, 2008, 10(2): 207-210.
[2] Britton JR. Altitude, oxygen and the definition of bronchopulmonary dysplasia[J]. J Perinatol, 2012, 32(11): 880-885.
[3] 党红星. 氧化应激与支气管肺发育不良研究进展[J]. 国际儿科学杂志, 2012, 39(5): 433-437.
[4] Guo WA, Knight PR, Raghavendran K. The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome[J]. Intensive Care Med, 2012, 38(10): 1588-1598.
[5] Christie JD, Shah CV, Kawut SM, et al. Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction[J]. Am J Respir Crit Care Med, 2009, 180(10): 1010-1015.
[6] Tian Z, Li Y, Ji P, et al. Mesenchymal stem cells protects hyperoxia-induced lung injury in newborn rats via inhibiting receptor for advanced glycation end-products/nuclear factor kappaB signaling[J]. Exp Biol Med(Maywood), 2013, 238(2): 242-247.
[7] 田兆方, 张志敏, 李玉红. GMCSF 对高氧暴露新生大鼠肺组织RAGE-NF-κB 通路的影响[J]. 中华医学杂志, 2011, 30(8): 2143-2147.
[8] Matute-Bello G, Winn RK, Jonas M, et al. Fas (CD95) induces alveolar epithelial cell apoptosis in vivo: implications for acute pulmonary inflammation[J]. Am J Pathol, 2001, 158(1): 153-161.
[9] 轩哲, 薛辛东, 富建华. 早产儿支气管肺发育不良的防治新进展[J]. 中国当代儿科杂志, 2010, 12(5): 412-416.
[10] Ambalavanan N, Mourani P. Pulmonary hypertension in bronchopulmonary dysplasia[J]. Birth Defects Res A Clin Mol Teratol, 2014, 100(3): 240-246.
[11] Yatime L, Andersen GR. Structural insights into the oligomerization mode of the human receptor for advanced glycation end-products[J]. FEBS J, 2013, 280(24): 6556-6568.
[12] Reynolds PR, Wasley KM, Allison CH. Diesel particulate matter induces receptor for advanced glycation end-products(RAGE) expression in pulmonary epithelial cells, and RAGE signaling influences NF-kappaB-mediated inflammation[J]. Environ Health Perspect, 2011, 119(3): 332-336.
[13] 吉萍, 俞敏. 晚期糖基化终末产物受体与肺发育及肺损伤[J]. 国际儿科学杂志, 2013, 40(5): 454-457.
[14] Lizotte PP, Hanford LE, Enghild JJ, et al. Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung[J]. BMC Dev Biol, 2007, 7: 15.
[15] THOMAS W, SPEER CP, 钱莉玲, 等. 支气管肺发育不良的防治—证据及临床应用[J]. 中国当代儿科杂志, 2007, 9(3): 276-277.
[16] 齐骥. 糖皮质激素防治早产儿支气管肺发育不良的进展及争议[J]. 中国循证儿科杂志, 2011, 6(3): 237-240.
[17] Su X, Looney MR, Gupta N, et al. Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury[J]. Am J Physiol Lung Cell Mol Physiol, 2009, 297(1): L1-L5.
[18] Iwamoto H, Gao J, Pulkkinen V, et al. Soluble receptor for advanced glycation end-products and progression of airway disease[J]. BMC Pulm Med, 2014, 14: 68.