摘要
目的:探讨急性胰腺炎(AP)致急性肺损伤(ALI)时肺泡巨噬细胞(AM)中肿瘤抑制因子cylindromatosis(CYLD)的表达及其与NF-κB炎症反应信号通路的关系。方法:60只成年SD大鼠随机均分为实验组与对照组;经支气管肺泡灌洗获取大鼠AM后,实验组给予TNF-α刺激(AP致ALI体外模拟),对照组给予等量生理盐水,每组AM分别在处理后0、1、3、6、12h,行相关炎性因子,以及CYLD、NF-κBp65、NF-κB必须调节蛋白(NEMO)及IκBα蛋白表达检测。结果:对照组各时间点上,AM中释放的各炎症因子、以及CYLD、NF-κB通路相关蛋白的表达水平均无明显变化(均P>0.05)。与对照组比较,实验组各项指标在0h均无差异(均P>0.05),但其后时间点均有统计学差异(均P<0.05);TNF-α、IL-1β、IL-6、NO的释放均在1h明显升高,且达到峰值,其后缓慢下降;从1h开始,CYLD蛋白表达明显下调、NF-κBp65和IκBα蛋白表达明显上调,其后均有所恢复;NEMO蛋白表达从1h明显上调,3h时表达降低,6、12h表达量再次回升。实验组AM中CYLD与NF-κBp65、NEMO及IκBα的表达呈明显负相关(r=-0.759、-0.849、-0.813,均P<0.05)。结论:AM中CYLD的表达可能在AP致ALI时降低,进而其对NF-κB炎症反应信号通路的抑制减弱。上调CYLD的表达可能是减轻AP致ALI的有效途径。
Objective： To investigate the expression of tumor suppressor factor cylindromatosis（CYLD） in alveolar macrophages（AMs） and its relation with NF-κB-dependent inflammatory signaling pathway during acute lung injury（ALI） caused by acute pancreatitis（AP）.Methods： Sixty adult SD rats were equally randomized into experimental group and control group. AMs were harvested by bronchoalveolar lavage, which were treated with TNF-α（for simulation of AP-induced ALI in vitro） in experimental group, and treated with the same amount of normal saline in control group, respectively. In these AMs, the levels of inflammatory factors and the expressions of CYLD, NF-κBp65, NF-κB-essential modulator（NEMO） and IκBα were determined at 0, 1, 3, 6 and 12 h after treatment.Results： At each time point, the releasing levels of all the determined inflammatory factors and expression levels of CYLD and NF-κB pathway-related proteins showed no significant change in control group（all P〉0.05）. In experimental group compared with control group, all parameters showed no significant difference at 0-h time point（all P〉0.05）, but had statistical difference at all the later time points（all P〈0.05）; the releasing levels of TNF-α, IL-1β, IL-6 and NO were all significantly increased and reached their peak values at 1-h time point and then gradually decreased; from 1-h time point, the CYLD expression was significantly down-regulated, while the expressions of NF-κBp65 and IκBα were significantly up-regulated, and then all were slightly recovered later; the NEMO expression was significantly up-regulated at 1-h time point, and declined at 3-h time point, and was elevated again at 6- and 12-h time point. CYLD expression had significantly negative correlation with the expressions of NF-κBp65, NEMO and IκBα in the AMs of experimental group（r=–0.759, –0.849, and –0.813, all P〈0.05） respectively.Conclusion： CYLD expression may be decreased in the AMs during ALI secondary to AP, thus its inhibition to NF-κB-dependent inflammatory signaling pathway is lessened. Up-regulating CYLD expression may probably be an effective approach for alleviating AP-induced ALI.
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2016年第3期357-362,共6页
China Journal of General Surgery
基金
北京市卫生系统高层次卫生技术人才培养计划基金资助项目(2011-3-033)
