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

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（5mg／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1d开始腹腔注入0．5％激动素（0．5mL／100g），每日1次。分别于第3、7、14、28d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）、PAl．1含量。结果模型组第7d肺泡炎最明显，到28d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7d时HYP含量开始升高，28d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3d开始下降，至7d时最低，14d仍显著低于其他两组（P〈0．05），28d时三组间无明显差异（P〉0．05）。模型组血浆u-PA水平在第3d开始下降，至7d时最低，与其他两组比较有显著差异（P〈0．05），14d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14d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3d开始升高，至7d时最高，14d时仍显著高于其他两组（P〈0．05），28d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14d时无显著差异（P〉0．05）。模型组血浆PAI-1在第3d开始升高，至7d时最高，显著高于其他两组（P〈0．05），但14d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。

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

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-PA, but the t-PA plasma contents in group B were still significantly lower than those in group A on the 14^th day （ P 〈 0. 05 ）. The PAI-1 contents of lung tissue in group B began to increase on the 3^rd day, reached the maximum on the 7^th day ,was still significantly higher than those in other two groups （ P 〈 0.05 ） , and there was no significant difference among three groups on the 14^th day. The PAI-1 contents in group C decreased compared with those in group B （P 〈 0. 05 ）, but still higher than those in group A （ P 〈 0. 05 ）, and there was no difference among them on the 14^th day. The PAI-1 plasma contents in group B began to increase on the 3rd day, reached the maximum and was significantly higher than other two groups on the 7^th day （P 〈 0.05 ） , and there was no significant difference among three groups on the 14＇h day. Conclusion The contents of u-PA and t-PA are increased by inhibiting PAI-1 generation in lung tissue through kinetin treatment, so that, kinetin can suppress pulmonary fibrosis induced by BLM-A5.