肺纤维化大鼠肺组织血小板源性生长因子和纤溶酶原激活物抑制剂1表达的研究

目的 观察肺纤维化大鼠肺组织中血小板源性生长因子(PDGF)和纤溶酶原激活物抑制剂1(PAI-1)表达的变化,探讨其在肺纤维化中的作用机制.方法 30只 Wistar大鼠随机分为博莱霉素组(BLM组)和对照组(NS组):①BLM组,气管内灌注BLM(5 mg/kg)诱导肺纤维化;②NS组,气管内灌注NS(剂量与用法同上).于气管内灌注后第7、14和28天各分别处死5只大鼠,取右肺支气管肺泡灌洗液(BALF),进行细胞分类、计数;留取左肺组织匀浆测定羟脯氨酸含量;采用免疫组织化学法测定PDGF和PAI-l蛋白的表达.结果 ①BLM组肺组织中胶原含量在第7天开始升高,第14、28天进行性增高,明显高于NS组(P＜0.01);②BLM组肺组织中PDGF蛋白表达在第7天达高峰,之后下降,第28天时仍高于NS组(P ＜0.05),与BALF中的细胞总数密切相关;③BLM组肺组织中PAI-1的表达在第7天开始升高,第28天达到高峰,与肺组织中胶原的含量密切相关(r=0.952,P＜0.01).结论 PDGF和PAI-1可能通过影响细胞外基质的代谢及胶原的沉积促进肺纤维化的发生.

Expressions of platelet derived growth factor and plaminogen activator inhibitor-1 in lung tissue of pulmonary fibrosis rats induced by bleomycin

Objective To study the expression of platelet derived growth factor and plaminogen activator inhibitor-1 in lung tissue of pulmonary fibrosis models induced by bleomycin in rat,and discuss the possible mechanism.Methods Thirty Wistar rats were randomly divided into two groups(15 in each group),bleomycin group(BLM group)and control group(NS group).①BLM group was intratracheally instilled with belomycin(BLM)(5 mg/kg)for pulmonary fibrosis.②NS group was intratracheally instilled with saline(5 mg/kg).Five rats in each group were sacrificed at 7.14,and 28 days after intratrachel instillation,BALF of right lung was taken for cell classification and calculation.Collagen content of the left lung tissue was assessed by hydroxyproline concentration.The expressions of PDGF and PAI-1 protein were assessed by immunohistochemistry.Results ①The collagen in BLM group significantly increased compared with that in NS group at day 7(P＜0.01);at day 14 and 28 the collagen continued to elevate.and there was significant difference compared with that in NS group(P＜0.01);②the expression of PDGF protein in BLM group after administraton of bleomycin was the highest at day 7 and then declined,but still elevated over NS group at day 2 8(P＜0.05);the expression of PAI-1 protein was significantly increased in BLM group at day 7.and was the highest at day 28.The expession was correlated with the collagen of lung(r=0.952,P＜0.01).Conclusions The deposition of collagen in lung might be the mechanism of PDGF and PAI-1 protein leading to pulmonary fibrosis.