摘要
目的:探讨雾化吸入柠檬酸对贫铀(DU)致大鼠肺成纤维细胞增生的影响及其机制。方法:取大鼠随机分为生理盐水组、模型组和柠檬酸组,后2组灌肺给予贫铀建模。柠檬酸组建模30min后雾化吸入20%柠檬酸,流量为1.44mL.min-1,每日1次,每次20min,连续给药7d。采用湿消化法检测各组大鼠建模给药后第7、15、30天(n=13)时肺铀含量,观察肺组织病理学变化及肺间质胶原沉积情况,免疫组化法检测肺泡区基质金属蛋白酶9(MMP-9)及其组织金属蛋白酶抑制物1(TIMP-1)表达情况。结果:与生理盐水组比较,模型组大鼠肺铀含量和MMP-9、TIMP-1表达均明显增加(P<0.05),且随时间延长肺铀含量逐渐降低;与模型组同时间点比较,柠檬酸组3个时间点肺铀含量和15、30d时MMP-9、TIMP-1表达均明显降低(P<0.05或P<0.01),且柠檬酸组15、30d时MMP-9、TIMP-1表达与生理盐水组比较无明显差异(P>0.05);模型组大鼠15、30d时肺成纤维细胞明显增生、肺间质胶原沉积明显,与其相同时间点比较,柠檬酸组15、30d时增生、沉积均减轻。结论:雾化吸入柠檬酸对贫铀致大鼠肺损伤具有保护作用,其可能机制是降低成纤维细胞增生。
OBJECTIVE： To investigate the effects of aerosol inhalation of citric acid on lung fibroblast proliferation in rat in duced by depleted uranium （DU） and its mechanism. METHODS： Wistar rats were randomly divided into normal saline group, model group and citric acid group. The latter 2 groups were given intrapulmonic administration of DU to establish lung fibroblast proliferation model. 30 min after modeling, citric acid group was given aerosol inhalation of 20% citric acid for 20 min at the flow rate of 1.44 mL.min1 once a day for consecutive 7 days. The contents of DU in lung tissue were determined by wet digestion meth od on 7th, 15th and 30th day after modeling. To observe histopathology change of lung tissue and the deposition of collagen in in terstitial tissue; the expressions of MMP9 and TIMP1 in pulmonary alveolus matrix were determined by immunohistochemical as say. RESULTS： Compared with normal saline group, the contents of DU in lung tissue and the expressions of MMP9 and TIMP1 were increased significantly in model group （P〈0.05）, the contents of DU were decreased gradually with the time increased; com pared with model group at corresponding time, the contents of DU in lung tissue on 7th, 15th and 30th day after modeling and the expressions of MMP9 and TIMP1 on 15th and 30th day after modeling were decreased significantly in citric acid group （P〈0.05 or P〈0.01）, and the expressions of MMP9 and TIMP1 on 15th and 30th day after modeling had no significant difference be tween citric acid group and normal saline group （P〉0.05） ; the significant deposition of collagen in interstitial tissue and signifi cant lung fibroblast proliferation were found in model group on 15th and 30th day after modeling, but the deposition of collagen and lung fibroblast proliferation in citric acid group were relieved, compared with model group at corresponding time. CONCLU SION： Due to inhibiting fibroblast proliferation, aerosol inhalation of citric acid attenuates the rat lung injury induced by DU.
出处
《中国药房》
CAS
CSCD
2012年第25期2313-2315,共3页
China Pharmacy
基金
国家自然科学基金资助项目(30873205)
关键词
贫铀
柠檬酸
雾化吸入
大鼠
成纤维细胞
Depleted uranium
Citric acid
Aerosol inhalation
Rats
Fibroblast
