摘要
目的观察地塞米松(dexamethasone,DXM)对肺纤维化大鼠肺组织信号传导子和转录活化子1(STAT1)和血小板源性生长因子(PDGF)表达的影响,探讨其抗纤维化的作用机制。方法45只Wistar大鼠随机分为地塞米松组(DXM组)、博来霉素组(BLM组)和对照组(NS组):①DXM组,气管内灌注BLM(5mg/kg,用生理盐水配制BLM溶液浓度为5mg/ml)诱导肺纤维化,随后每日用地塞米松3mg/kg腹腔注射进行干预;②BLM组,气管内灌注BLM(剂量与用法同上),随后每日用生理盐水(NS)3mg/kg腹腔注射进行干预;③NS组,气管内灌注和腹腔注射均用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;采用免疫组织化学法测定STAT1和PDGF蛋白的表达。结果①BLM组BALF中细胞总数在第7天达到高峰,第14天和第28天开始下降;DXM不同时间组细胞总数均低于BLM组,尤其以第7天差异明显(P<0.05);②BLM组肺组织中STAT1和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),均与BALF中的细胞总数呈正相关(r=0.880和0.902,P均<0.01);DEX组STAT1和PDGF蛋白表达明显低于同期BLM组(P<0.01)。结论地塞米松能够抑制BLM诱导的肺泡炎和肺纤维化程度,其机制可能通过早期抑制肺组织STAT1和PDGF的表达而发挥作用。
Objective To study the effect of dexamethasonc on pulmonary, fibrosis model induced by bleomycin in rats and the expression of STAT1 and PDGF in lung tissue, and to discuss the possible mechanism. Methods Forty - five Wistar rats were randomly divided into three groups （15 in each group）. They were dexamethasone group （DXM group） , bteomycin group （BLM group） and control group （NS group） （1） The DEX group were intratracheally instilled with belomycin （BLM） （5mg/kg,in l ml 0. 9% NaCl solution） , and then were treated with dexamethasone 3mg/kg via celiac injection daily;（2） BLM group were intratracheally instilled with B LM （5mg/kg） , and then were treated with saline 3mg/kg via celiac injection daily;（3） NS group were intratracheally instilled with saline （5mg/kg） , and then were treated with saline 3mg/kg via celiac injection daily. Five rats in each group were sacrificed at 7,14,and 28 days after intratra- chel instillation. Histological changes of the lungs were evaluated by HE stain. The bronehoalveolar lavage fluid （BALF） of right lung was gotten and the cells counting as well as differentiation were figured out. The expression of STAT1 and PDGF protein was assessed by im- munohistoehemistry. Results （ 1 ） The total number of inflammatory cells in BALF in BLM group was the highest at day 7 and diminished at day 14 and 28, which was significant different compared with that of the NS group（ P 〈 0. 01 ）. The total number of inflammatory cells in BALF in DEX group was significantly less than that in related subgroups of BLM, especially at day 7 （P 〈 0. 05 ）. （2） The expression of STAT1 and PDGF protein in BLM group after bleomycin administration was 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. 892 and 0. 902, P 〈 0.01 ）. （ 3 ） The expression of STAT1 and PDGF in DEX group all reduced significantly as compared with that in BLM group. Conclusion Dexamethasone can reduce the extent of alveolitis and fibrosis in bleomycin - induced pulmonary fibrosis in rats. It can also reduce the injury of lung. It suggests that the inhibition of STAT1 and PDGF protein in lung may be the mechanism of dexamethasone to treat pulmonary fibrosis.
出处
《医学研究杂志》
2009年第2期40-42,116,共4页
Journal of Medical Research
基金
四川省卫生厅资助项目(0447)
滨州医学院科技计划(BY2006KJ04)
关键词
肺纤维化
博来霉素
地塞米松
信号传导子和转录活化子1
血小板源性生长因子
Pulmonary fibrosis
Bleomycin
Dexamethasone
Signal transduction and activation of transcription - 1 （ STAT1 ）
Platelet derived growth factor （PDGF）
作者简介
通讯作者：范贤明，电子信箱：fxm129@163．com.
