Inhibitory effect of aminoguanidine on bleomycin-induced pulmonary toxicity in rat  

氨基胍对博莱霉素诱发大鼠肺毒性的抑制作用(英文)

作　　者：陈晓玲[1] 黄善生[1] 李文斌[1] 王殿华 王新良[1] 

机构地区：[1]河北医科大学基础医学研究所病生研究室,石家庄中国050017

出　　处：《Acta Pharmacologica Sinica》2001年第8期711-715,共5页中国药理学报（英文版）

摘　　要：AIM: To observe the inhibitory effect of aminoguanidin (AG) on the pulmonary toxicity induced by bleomycin A5(BLM-A5) in rat. METHODS: The contents of hy-droxyproline, nitrite/nitrate (NO2/NO3 ), and malondi-aldehyde (MDA), which reflect fibrosis, nitric oxide (NO) production, and hyperoxidative injury of lung, were investigated by colorimetry. Histologic and mor-phometric examination of lung was also carried out on histological sections stained with hematoxylin and eosin (HE). RESULTS: (1) The content of hydroxyproline in lung and MDA in out-going pulmonary blood (OPB) increased from 14 d to 30 d after intratracheal administration of BLM-A5. Collapsed alveoli and fibrotic areas were seen and a lot of fibroblasts appeared in the lung in-terstitum of the rats 30 d after BLM-A5. (2) The NO2 / NO3- content increased in supernatant of alveolar macro-phage culture and in OPB. (3) The increment of hydroxyproline in lung and MDA in OPB induced by BLM-A5 was alleviated by aminoguanidine (AG, 20 mg-kg-1-d-1, ip). AG also reduced the histologic and morphometric changes in lung interstitum. (4) The augment of NO2 /NO3- in OPB was blocked by AG. CONCLUSION: AG had inhibitory effect on pulmonary injury and fibrosis induced by BLM- A5, and the inhibitory effect was related to the decrease of NO production in lung.目的:观察氨基胍(AG)对博莱霉素A_5(BLMA_5)诱发大鼠肺毒性作用的影响。方法:BLM-A_5(5mg·kg^(-1))气管滴注诱发大鼠肺损伤和肺纤维化形成;在气管滴注BLM-A_5的同时及之后21d腹腔注射AG(20mg·kg^(-1)·d^(-1),ip)。化学比色法测定肺组织羟脯氨酸含量、肺泡巨噬细胞培养上清液中NO_2^-/NO_3^-含量、出肺血中NO_2^-/NO_3^-含量;HE染色组织切片上观察组织形态学变化。结果:(1)滴注BLM-A_5后d14至30,肺组织羟脯氨酸含量和出肺血中的MDA含量逐渐升高;注BLMA_5后d30,肺间质可见萎陷的和纤维化的肺泡,并出现大量的成纤维细胞。(2)滴注BLM-A_5后d7至14,出肺血NO_2^-/NO_3^-含量升高;肺泡灌流液中巨噬细胞培养上清液中NO_2^-/NO_3^-含量升高。(3)AG明显抑制出肺血MDA含量和肺羟脯氨酸含量的升高;AG还减轻肺间质组织形态学变化。(4)AG明显抑制出肺血NO_2^-/NO_3^-含量的升高。结论:AG对BLM-A_5诱发的大鼠肺损伤和纤维化有抑制作用,此作用与其抑制肺内NO大量生成有关。

关 键 词：BLEOMYCIN TOXICITY pulmonary fibrosis GUANIDINES 

分 类 号：R96[医药卫生—药理学]