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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 cylindromatosis (CYLD) in alveolar macrophages (AM) induced by acute pancreatitis (AP) and its relationship with NF-κB inflammatory signal transduction pathway. Methods: Sixty adult Sprague-Dawley rats were randomly divided into experimental group and control group. After AM was obtained by bronchoalveolar lavage, the experimental group was given TNF-α stimulation (AP induced ALI in vitro simulation), and the control group was given equal amount of physiology Saline, and each group of AM was treated with 0, 1, 3, 6, 12 h after treatment. The expression of CYLD, NF-κBp65, NEMO and IκBα protein were detected. Results: At each time point, there were no significant changes in the expression of all the inflammatory cytokines and the expressions of CYLD and NF-κB pathway related proteins (P> 0.05). Compared with the control group, there was no significant difference in the indexes of the experimental group at 0h (all P> 0.05), but there were significant differences at the later time points (all P <0.05); while the levels of TNF-α, IL- , NO release increased significantly at 1h, and peaked, and then decreased slowly. From 1h, the expression of CYLD protein was significantly down-regulated and the expressions of NF-κBp65 and IκBα were significantly up-regulated. The expression of NEMO protein From 1h significantly increased, 3h expression decreased, 6,12h expression again rise. There was a significant negative correlation between CYLD and the expression of NF-κBp65, NEMO and IκBα in experimental group (r = -0.759, -0.849, -0.813, all P <0.05). CONCLUSIONS: The expression of CYLD in AM may decrease when ALI is induced by AP, and then the inhibition of NF-κB signaling pathway is weakened. Upregulation of CYLD expression may be an effective way to reduce AP-induced ALI.