血管活性肠肽对LPS诱导大鼠肺泡巨噬细胞表达MMP-9的影响  

Effects of vasoactive intestinal peptide on LPS-induced MMP-9 expression by alveolar macrophages in rats

作　　者：刘永平[1] 管茶香[1] 白洪波[1] 秦晓群[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）》2005年第6期645-649,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(39800053);湖南省卫生研究课题(2003-B-205)

摘　　要：目的:探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对经脂多糖(lipopolysaccharide,LPS)诱导大鼠肺泡巨噬细胞分泌和表达基质金属蛋白酶-9(MMP-9)的影响.方法:采用逆转录聚合酶链式反应(RT-PCR)及明胶酶谱法(gelatin zymography),观察经LPS诱导的大鼠肺泡巨噬细胞给予不同浓度的VIP(10-10～10-6 mol/L)作用24 h后MMP-9基因表达量和活性的变化.结果:(1)正常肺泡巨噬细胞仅分泌和表达少量的MMP-9,经不同浓度LPS(0.1～10 mg/L)诱导后MMP-9活性和表达均明显高于未经LPS诱导的对照组(P<0.01);(2)不同浓度VIP (10-10～10-6 mol/L)的干预,均可下调LPS诱导的MMP-9的活性和表达(P<0.01);(3)该作用可被蛋白激酶C和钙调蛋白的相应阻断剂H-7,W-7部分逆转(P<0.01).结论:VIP能降低LPS诱导的大鼠肺泡巨噬细胞MMP-9的表达及活性,其细胞内信号途径可能与蛋白激酶C和钙调蛋白有关,提示VIP在肺内炎症时可能具有保护性作用.Objective To explore the role of vasoactive intestinal peptide （VIP） on LPS-induced MMP-9 expression by alveolar macrophages （AM） in rats. Methods LPS-induced cultured Wistar rats AMs were treated with different concentrations of VIP （ 10^-10～10^-6mol/L） for 24 h. AMs and the supernatant were collected to measure the MMP-9 expression and activity by RT-PCR and gelatin zymography, respectively. Results The MMP-9 activity and expression of LPS-induced AMs were significantly higher than those in the control group （P〈0.01 ）. VIP （ 10^-9～10^-6mol/L） down-regulated LPS-induced MMP-9 activity and its expression. The effects were diminished by H-7 and W-7, an antagonist of protein kinase C （PKC） and calmodulin （CAM） （P 〈0.01）. Conclusion VIP can decrease LPS-induced MMP-9 activity and its expression, which may be related to protein kinase C and calmodulin pathway. VIP may have protective roles in the lung injury.

关 键 词：血管活性肠肽 肺泡巨噬细胞 基质金属蛋白酶-9 脂多糖 

分 类 号：R563[医药卫生—呼吸系统]