摘要
目的探讨蛋白酪氨酸激酶(JAK)信号传导子和转录活化子1(STAT1)信号转导通路在肺纤维化中的作用机制。方法将30只Wistar大鼠随机分为博莱霉素(BLM)组和生理盐水(NS)组,分别于气管内灌注BLM及NS后第7、14、28天处死。右肺支气管肺泡灌洗,进行细胞分类、计数;左肺组织匀浆测定胶原含量;免疫组化法测定STAT1、血小板源性生长因子(PDGF)和纤溶酶原激活物抑制剂1(PAI-1)蛋白的表达。结果BLM组肺组织胶原含量在7、14、28 d均明显高于NS组(P<0.01);BLM组肺组织STAT1、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),且与支气管肺泡灌洗液中的细胞总数呈正相关(r=0.880,P均<0.01);BLM组肺组织中PAI-1表达在第7天开始升高,第28天达高峰,且与肺组织中胶原含量呈正相关(r=0.952,P<0.01)。结论JAK/STAT1信号转导通路可能通过调节STAT1、PDGF和PAI-1表达,参与肺纤维化的形成。
Objective To study the expressions of STAT1, PDGF and PAI-1 in lung tissue of rats pulmonary fibrosis model induced by bleomycin（BLM）, and discuss the possible mechanism of JAK and STAT1 pathway. Methods Thirty Wistar rats were randomly divided into two groups （ 15 in each group） ： BLM group and 0.9% NaCl solution （NS） group. The BLM group was intratracheally instilled with belomycin （5 mg/kg）. The NS group was intratracheally instilled with NS in the same volume. Five rats in each group were sacrificed at 7,14and 28 days after intratracheal instillation. The bronchoalveolar lavage fluid （BALF） of right lung was performed and the cell counting as well as differentiation were figured out. collagen contents of the left lung tissue were assessed by hydroxyproline concentration. Lung expressions of STAT1, PDGF and PAI-1 protein were assessed by immunohistochemistry. Results The collagen in BLM group significantly increased compared with NS group at day 7 ; At day 14 and 28 the collagen in BLM group continued to elevate, and there was significant difference compared with NS group（ P 〈 0.01 ）. The expressions of STAT1 and PDGF protein in BLM group after bleomycin administration were the highest at day 7 and still elevated over NS group at day 28, and they were correlated with the total number of cells in BALF, respectively（ r = 0. 880 ,P all 〈 0.01 ）. At day 7 the expression of PAI-1 protein was significantly increasing in BLM group, and was the highest at day 28. The expression of PAI-1 protein was correlated with the collagen contents of lung （r = 0.952,P 〈 0.01 ）. Conclusions There existed increased expressions of STAT1, PDGF and PAL1 protein in lung tissue in bIeomycin-induced pulmonary fibrosis rats. JAK and STAT1 pathway might take part in pulmonary fibrosis through increasing expressions of STAT1, PDGF and PAL1 protein.
出处
《山东医药》
CAS
北大核心
2008年第34期4-6,共3页
Shandong Medical Journal
基金
四川省卫生厅基金资助项目(040054)。
