激动素通过抑制纤溶酶原激活物抑制因子1减轻博莱霉素诱导的大鼠肺纤维化  

Kinetin Alleviates Bleomycin-induced Rats Pulmonary Fibrosis by Inhibiting Plasminogen Activator Inhibitor-1

作　　者：王欣燕[1] 黄坤[1] 康小文[1] 李兆国[1] 阳成成[1] 吴晓梅[1] 

机构地区：[1]哈尔滨医科大学第二附属医院呼吸内科,黑龙江哈尔滨150086

出　　处：《中国呼吸与危重监护杂志》2014年第1期44-48,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：黑龙江省卫生厅课题(编号:2009-121)

摘　　要：目的研究激动素对博莱霉素A5(BLM-A5)诱导的大鼠肺纤维化的干预作用。方法雌性Wistar大鼠60只随机分为对照组、模型组和治疗组,每组20只。模型组与治疗组大鼠经穿刺向气管内注入BLM-A5(5 mg/kg),对照组在相同条件下注入等体积生理盐水。治疗组于灌注BLM-A5的第1 d开始腹腔注入0.5%激动素(0.5 mL/100 g),每日1次。分别于第3、7、14、28 d处死大鼠,取肺组织病理切片行HE及Masson染色观察肺部炎症和纤维化情况,ELISA方法检测肺组织羟脯氨酸(HYP)含量及肺组织和血浆中尿激酶型纤溶酶原激活物(u-PA)、组织型纤溶酶原激活物(t-PA)、PAI-1含量。结果模型组第7 d肺泡炎最明显,到28 d时肺纤维化最严重;治疗组肺泡炎及肺纤维化程度均较模型组显著减轻,但仍较对照组严重(P<0.05)。模型组第7 d时HYP含量开始升高,28 d最高;各组变化趋势与肺纤维化变化相一致。模型组肺组织u-PA在第3 d开始下降,至7 d时最低,14 d仍显著低于其他两组(P<0.05),28 d时三组间无明显差异(P>0.05)。模型组血浆u-PA水平在第3 d开始下降,至7 d时最低,与其他两组比较有显著差异(P<0.05),14 d后三组之间无明显差异(P>0.05)。三组t-PA在肺组织和血浆中的含量变化与u-PA基本一致,但在14 d时模型组血浆t-PA含量仍较对照组显著降低(P<0.05)。模型组肺组织PAI-1在第3 d开始升高,至7 d时最高,14 d时仍显著高于其他两组(P<0.05),28 d时三组之间无明显差异(P>0.05);治疗组肺组织PAI-1水平较模型组下降(P<0.05),但仍高于对照组(P<0.05),至14 d时无显著差异(P>0.05)。模型组血浆PAI-1在第3 d开始升高,至7 d时最高,显著高于其他两组(P<0.05),但14 d后三组间无明显差异(P>0.05)。结论激动素通过抑制肺组织PAI-1生成,使u-PA、t-PA含量升高,减轻了博莱霉素A5所致的大鼠肺纤维化。Objective To investigate the therapeutic effect of kinetin on bleomycin A5 （ BLM-AS）- induced pulmonary fibrosis in rats. Methods Sixty female Wistar rats were randomly divided into three groups. Group A （ n = 20） was intratracheally injected with saline as control. Group B （ n = 20） were intratracheally injected with BLM-A5 to establish pulmonary fibrosis model. Group C （n = 20 ） was intratracheally injected with BLM-A5 and received intraperitoneal injection of kinetin at 0.5 mL/100 g once daily. The rats were sacrificed on the 3^rd,7th, 14th and 28th day respectively. HE and Masson staining were performed to observe lung pathological changes. The contents of hydroxyproline （ HYP）, urokinase-type plasminogen activator （u-PA）, tissue-type plasminogen activator （t-PA）, and PAl-1 in lung and plasma were measured by ELISA. Results Alveolitis was most obvious on the 7th day and pulmonary fibrosis was most severe on the 28^th day in group B compared with other two groups （P 〈0. 05）. Alveolitis and pulmonary fibrosis in group C were significantly alleviated compared with group B （P 〈 0. 05 ） , but still more severe than group A （P 〈0. 05）. The HYP contents in group B,eoineided with fibrosis,began to increase on the 7^th day and reached the peak on the 28^th day, significantly higher than those in other two groups （P 〈 0. 05 ）. The u-PA contents of lung tissue in group B began to decline on the 3^rd day,reached the minimum on the 7^th day, and was still significantly lower than those in other two groups （P 〈 0. 05）. On the 14^th day, the u-PA contents had no significant difference among three groups. The u-PA plasma contents in group B began to decline on the 3^rd day, reached the minimum and had significant difference compared with other two groups on the 7^th day （ P 〈0. 05 ） ,and there was no significantly difference among three groups after the 14^th day. The t-PA contents change of lung tissue and plasma in three groups were generally consistent with u

关 键 词：肺纤维化 激动素 纤溶酶原激活物抑制物1 尿激酶型纤溶酶原激活物 组 织型纤溶酶原激活物 

分 类 号：R965[医药卫生—药理学]