乌司他丁对博莱霉素诱导大鼠肺纤维化的保护作用  

Protective effects of ulinastatin on blemycin A5 - induced pulmonary fibrosis in rats

作　　者：李德军[1] 靳长俊[1] 纪洪生[1] 赵宝[1] 许春阳[1] 夏文君[1] 韩立会[1] 

机构地区：[1]山东大学附属省立医院外科监护室,山东济南250021

出　　处：《中国急救医学》2017年第9期827-829,共3页Chinese Journal of Critical Care Medicine

基　　金：山东省自然科学基金（ZR2011HM063）;天普研究基金（01201006）

摘　　要：目的 探讨乌司他丁（UTI）对博莱霉素诱导大鼠肺纤维化的保护作用。方法 雄性SPF级SD大鼠75只，随机分模型组和治疗组，气管内注入0.4%博莱霉素A5 0.25 mL（5 mg/kg） 诱导大鼠纤维化模型。造模次日常规SPF饲养，治疗组每日给予UTI（20 000 U/kg）治疗。各组动物分别在7、14、28 d处死，分离肺组织，10%中性福尔马林固定，备石蜡切片，进行组织学检查（HE染色）及转化生长因子-β1（TGF-β1）、肿瘤坏死因子-α（TNF-α）免疫组化染色。结果 ①肺组织病理学改变：对照组肺组织结构正常；模型组7 d时表现为肺泡炎,14 d肺泡炎加重,28 d广泛纤维化；治疗组经治疗后病变明显轻于模型组, 有正常肺泡结构存在，与模型组比较纤维化差异有统计学意义（P〈0.01）。②模型组TGF-β1、TNF-α持续高表达，28 d TGF-β1表达最多；治疗组TGF-β1、 TNF-α表达明显低于模型组（P〈0.01）。结论 UTI对博莱霉素A5肺纤维化模型的肺泡炎和肺纤维化有明显的治疗作用,其治疗机制可能主要是通过抑制炎症因子TGF-β1、TNF-α蛋白的表达而实现。Objective To investigate the therapeutic effect and mechanism of ulinastatin on blemycin A5 -induced pulmonary fibrosis in rats. Methods 75 rats were divided into normal group, model group and ulinastatin group. Rat pulmonary fibrosis was induced by intrabronchial injection of blemycin A5（5 mg/kg）. Treatment was started from day 2 to day 28 with ulinastatin（20 000 U/kg）. The pathological changes were observed by hematoxylin and eosin （HE） staining and expressions of transforming growth factor - β1 （TGF - β1 ） protein and tumor necrosis factor - αTNF -α） protein were tested by immunohistochemical technique. Results The pulmonary alveolitis and fibrosis were alleviated remarkable in the lung pathological section in ulinastatin group compared with those in the model group （P 〈 0.01 ）. The expression of TGF- β1 protein and TNF-α protein were decreased significantly than those in the model group （P 〈 0.01 ）. Conclusion Ulinastatin ameliorates the pulmonary fibrosis and its mechanisms may be through decreasing the expression levels of TGF -β1 protein and TNF - α protein.

关 键 词：肺间质纤维化 乌司他丁(UTI) 博莱霉素A5 转化生长因子-β1(TGF-β1) 肿瘤坏死因子-α(TNF-α) 

分 类 号：R285.5[医药卫生—中药学]