降钙素基因相关肽对LPS诱导肺泡巨噬细胞分泌MMP-9的影响

EFFECTS OF CGRP ON LPS-INDUCED MMP-9 SECRETION BY ALVEOLAR MACROPHAGES

目的探讨降钙素基因相关肽(CGRP)对经脂多糖(LPS)诱导大鼠肺泡巨噬细胞分泌基质金属蛋白酶-9(MMP-9)的影响及其机制。方法对经LPS诱导的大鼠肺泡巨噬细胞给予不同浓度的CGRP干预,并同时设置对照,分别收集上清液,采用明胶酶谱法测定LPS、CGRP或二者联合干预后大鼠肺泡巨噬细胞分泌MMP-9的变化。结果①正常肺泡巨噬细胞仅分泌少量MMP-9,各浓度CGRP对其分泌无影响,但经LPS诱导后MMP-9的分泌均明显升高(P<0.01);②不同浓度的CGRP干预呈剂量依赖方式降低LPS诱导的肺泡巨噬细胞MMP-9的分泌(P<0.01)。③CGRP下调LPS诱导的肺泡巨噬细胞MMP-9分泌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可明显下调LPS诱导的大鼠肺泡巨噬细胞MMP-9活性,其机制与蛋白激酶C及钙调蛋白信号途径有关。

To explore the effects of calcitonin-gene-related peptide （CGRP） on LPS-induced MMP-9 secretion by alveolar macrophages（AM） in uitro. Methods： The supematant of LPS-induced Wistar rat AM from different intervention groups were col-lected to measure the activity by gelatin zymography. Results： ①Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner（p〈 0.01 ）. ②The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group（p 〈0.01 ）. ③The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C（PKC） and calmodulin（CaM）（p〈 0.05）. Conclusion. These da-ta suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.