乌司他丁对放射性肺损伤模型大鼠干预作用及层黏连蛋白和羟脯氨酸的影响

Prevention effect of ulinastatin on radiation-induced lung fibrosis in rats

目的探讨乌司他丁对放射性肺损伤的治疗作用及层黏连蛋白（LN）和羟脯氨酸（Hyp）在放射性肺损伤中的变化。方法雌性SD大鼠100只随机分为3组：正常对照组（C组）24只，单纯照射组（R组）40只，乌司他丁治疗组（U组）36只。R组及U组动物麻醉后，行直线加速器全胸部照射一次，剂量为25Gy。U组照射后即按乌司他丁100000U／kg，尾静脉注射，而后每天以相同剂量尾静脉注射7d。C组和R组尾静脉注射等体积生理盐水。于照射后第7、15、30、60、90、150天处死动物，取部分肺组织行HE染色及Masson染色，观察组织学及肺胶原纤维等，使用放射免疫法检测血清中LN水平，碱水解法测定血清中Hyp的含量。结果U组大鼠生存率（88．9％）明显高于R组大鼠（62．5％）。R组大鼠肺部在照射后，早期肺泡明显出现充血和水肿，晚期部分肺泡腔塌陷，可见成纤维细胞构成的成纤维病灶，甚至大面积的肺完全实变；与R组相比，U组中、晚期充血、水肿及肺间隔增宽不明显，少见纤维化病灶及实变。R组血清中LN、Hyp水平随着照射时间逐渐增加，在150d时达到高峰，分别为（129．70±3．48）ng／ml、（193．70±5．41）ng／ml，这与肺部组织学变化趋势基本一致，U组与R组相比却明显减少（P〈0．01）。结论乌司他丁能有效治疗放射性肺损伤，为放射性肺损伤的防治提供了一种新的方法。

Objective To evaluate the effects of ulinastatin on radiation-induced pulmonary fibrosis in Sprague-Dawley（SD） rats and changes of laminin（LN） and hydroxyproline（Hyp） in radiation-induced pulmonary fibrosis. Methods One hundred female SD rats were randomly divided into three groups：group without irradiation or ulinastatin（group C）, group treated with ulinastatin after radiation（group U）, group only received thoracic irradiation（group R）. Whole lungs of rats in group R and group U were irradiated with a total dose of 25 Gy by linear accelerator. The rats were sacrificed on 7, 15,30,60, 90,150 days after irradiation. Radioimmunity was used to determine LN. Colorimetric assay was used to detect the protein level of Hyp. Results Hyp and LN levels significantly increased, severe inflammatory reaction and pulmonary fibrosis developed in rats only receiving thoracic irradiation,however,administration of ulinastatin prevented the inflammatory process and pulmonary fibrosis. Conclusions LN and Hyp play an important role in radiation-induced lung fibrosis,which could be prediction of radiation-induced lung fibrosis. Ulinastatin plays a protective and regulative role on pulmonary fibrosis of rats, which may serve as a novel therapeutic strategy.