烟雾暴露对大鼠肺血管壁碱性成纤维细胞生长因子及基质金属蛋白酶12表达的影响

Effects of cigarette smoke exposure on expression of basic fibroblast growth factor and matrix metalloproteinase-12 in pulmonary vascular of rats

目的观察碱性成纤维细胞生长因子（basicfibroblastgrowthfactor，bFGF）及基质金属蛋白酶12（matrixmetalloproteinase-12，MMP12）在烟雾暴露大鼠肺血管壁上的表达情况，并探讨它们在肺血管重塑中的作用。方法40只雄性SD大鼠按随机数字表法分为对照组（C组）、烟雾暴露1月组（Slm组）、烟雾暴露2月组（S2m组）、烟雾暴露3月组（S3m组），每组10只，建立烟雾暴露大鼠模型。HE染色观察肺动脉组织形态学改变并测量各组大鼠肺血管管壁厚度占血管外径的百分比（WT％）及管壁面积占血管总面积的百分比（WA％）；VG染色观察胶原纤维增生情况；免疫组织化学染色检测bFGF和MMP12在肺血管壁的表达，用平均灰度值反映蛋白表达量，并分别分析bFGF与WT％、WA％的相关性，MMP-12与WT％、WA％的相关性，以及bFGF与MMP12的相关性。结果①随着烟雾暴露时间的延长，WT％、WA％值逐渐增高，各组间比较差异均有统计学意义（P〈0．05）②随着烟雾暴露时间的延长．bFGF、MMP—12蛋白表达的阳性率增加，各组问差异均有统计学意义（P〈0．05）。③bFGF与wT％（r=-0．748，P〈0．05）、WA％（r=-0．834，P〈0．05）呈正相关，MMP-12与WT％（r=-0．565，P〈0．05）、WA％（r=-0．504，P〈0．05）呈正相关，bFGF与MMP-12呈正相关（r=0．738，Pd0．05）。结论烟雾暴露町以上调肺血管壁bFGF、MMP-12蛋白的表达，这可能在烟雾暴露大鼠所致肺血管重塑的发生机制中发挥一定作用。

Objective To observe the expression of basic fibroblast growth factor （bFGF） and matrix metalloproteinase-12 （MMP-12） in puhnonary vascular wall induced by cigarette smoke exposure in rats, and to explore their role in pulmonary vascular remodeling. Methods 40 male SD rats were randomly divided into control group, smoke exposure for one month group, smoke exposure for two months group, smoke exposure for three months group, with ten rats in each group. The ratio of pulmonary vascular wall thickness and vascular external diameter （WT%）, and the ratio of pulmonary vascular wall area and total pulmonary vascular area （WA%） were measured by the image analysis system. The collagen fiber formation was observed by Van Gieson staining. The expressions of bFGF and MMP 12 in pulmonary vascular wall were detected by immunohistochemical staining, the protein expression was reflected by average grey value. Results （1） As the extension of smoke exposure time, WT% and WA% were increased gradually, there was statistical significance among groups （ P 〈0.05）. （2）As the extension of smoke exposure time,bFGF and MMP 12 protein expressions increased, there was statistical significance among groups （ P 〈0.05）. （3）bFGF was positivily correlated with WT% （ r = -0. 748, P 〈 0.05） and WA% （r = -0. 834, P 〈 0.05）, MMP-12 was positivily correlated with WT% （r =-0. 565, P d0.05） and WA% （ r =-0. 504, P d0.05）,bFGF was positively related with MMP-12 （ r =0. 738, P〈0.05）. Conclusions By upregulating the expressions of bFGF and MMP-12 protein in pulmonary vascular,cigarette smoke exposure induces the remodeling of pulmonary vascular.