降钙素基因相关肽对人支气管上皮细胞分泌MMP-9的影响  

Effect of calcitonin-gene-related peptide on MMP-9 production in human bronchial epithelial cells

作　　者：管茶香[1] 刘永平[1] 崔艳茹[1] 于芳[1] 孙国瑛[1] 刘惠君[1] 

机构地区：[1]中南大学湘雅医学院生理学系,长沙410078

出　　处：《中南大学学报（医学版）》2007年第5期771-775,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(39800053)~~

摘　　要：目的:探讨降钙素基因相关肽(calcitonin-gene-related peptide,CGRP)对人支气管上皮细胞分泌基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)/明胶酶B的影响及其机制。方法:采用逆转录聚合酶链式反应及明胶酶谱法,观察给予不同浓度的CGRP(10-10～10-6mol/L)刺激及CGRP10-6mol/L刺激后不同时间点(6,12,18,24,36和48h)MMP-9活性和基因表达量的变化。结果:体外培养的人支气管上皮细胞能分泌MMP-9;CGRP干预呈剂量及时间依赖方式上调人支气管上皮细胞MMP-9的活性和MMP-9 mRNA的表达(P<0.01);CGRP上调人支气管上皮细胞MMP-9活性和表达的作用可为蛋白激酶C阻断剂H-7及钙调蛋白阻断剂W-7部分逆转(P<0.05)。结论:CGRP可明显上调人支气管上皮细胞MMP-9的活性和表达,其胞内信号转导机制与蛋白激酶和钙调蛋白信号途径有关。Objective To examine the expression of matrix metalloproteinase-9 （ MMP-9 ） in human bronchial epithelial cells treated with calcitonin-gene-related peptide （CGRP）. Methods RT-PCR and gelatin zymography were performed to examine the dynamic expression and activity of MMP-9 in human bronchial epithelial cells at different doses （10^-10, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L） and different time points （ 6,12,18,24,36, and 48 h） after the stimulation of CGRP. Results The unstimulated human bronchial epithelial cells only secreted a small amount of MMP-9. After the CGRP stimulation, the expression of MMP-9 presented in a concentration-dependent （10^-l0, 10^-9, 10^-8, 10^-7, and 10^-6mol/L） and time-dependent （6,12,18,24,36, and 48 h ） manners （ P 〈 0.01 ） in human bronchial epithelial cells. The effect of CGRP could be dimin- ished by H-7 and W-7, an antagonist of protein kinase C （PKC） and calmodulin （CAM） （P 〈 0.05 ）. Conclusion CGRP can stimulate the secretion and expression of MMP-9 in human bronchial epithelial cells, and the signal transduction is partly via the PKC and CaM pathway.

关 键 词：降钙素基因相关肽 人支气管上皮细胞 基质金属蛋白酶-9 

分 类 号：R363[医药卫生—病理学]