雾化吸入氨基胍防止肺纤维化大鼠肺内结缔组织生长因子上调  

Inhalation of aminoguanidine prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats

作　　者：郭红[1] 陈晓玲[1] 陈超[2] 金辉[3] 李淑琴[1] 

机构地区：[1]河北医科大学基础医学研究所病理生理研究室,石家庄050017 [2]河北医科大学药学院药理研究室,石家庄050017 [3]河北医科大学临床学院实验中心,石家庄050017

出　　处：《生理学报》2009年第4期361-366,共6页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.30570789);Natural Science Foundation of Hebei Province;China(No.C2004000582)

摘　　要：本研究观察了雾化吸入氨基胍(aminoguanidine,AG)对博莱霉素(bleomycin,BLM)所致肺纤维化大鼠肺内结缔组织生长因子(connective tissuegrowth factor,CTGF)上调的影响。大鼠气管内一次性滴注BLM复制肺纤维化动物模型,以气管内滴注等容积的生理盐水(normal saline,NS)作对照。在气管滴注BLM后第1天至第30天期间,给大鼠雾化吸入AG(2mmol/L、10mmol/L或50mmol/L,5min/次,一天两次),以雾化吸入NS作对照。采用硝酸还原法、氯胺-T法、Masson染色法、Western blot和RT-PCR分别检测出肺血浆NO2-/NO3-含量(代表NO含量)、肺羟脯氨酸含量、肺胶原纤维含量以及肺CTGF蛋白和mRNA含量。结果显示:气管滴注BLM后第14天大鼠出肺血浆中NO2-/NO3-含量、气管滴注BLM后第30天大鼠的肺羟脯氨酸含量、肺胶原纤维含量、肺CTGF蛋白和mRNA水平均高于相应的对照组大鼠(均P<0.01);上述指标均在雾化吸入10mmol/L和50mmol/L AG后有所改善(出肺血浆中NO2-/NO3-含量P<0.01,其余均P<0.05)。以上结果表明,AG能有效地防止肺纤维化大鼠肺内CTGF的上调,这可能是其防止肺纤维化形成的作用机制之一。Connective tissue growth factor （CTGF） is a known profibrotic cytokine. The purpose of the present study was to explore the effects of inhalation of aminoguanidine （AG） on the up-regulation of connective tissue growth factor （CTGF） in fibrotic lungs of rats. Sprague-Dawley rats received single intratracheal instillation of bleomycin （BLM） or instillation of the same volume of normal saline （NS） as control. From day 1 to day 30 after intratracheal BLM instillation, the rats inhaled AG （2, 10 or 50 retool/L, 5 min/each time） twice a day or inhaled the same volume of NS as vehicle control. The change of nitric oxide （NO） content in lungs was evaluated by nitrite/nitrate （NO2^-/NO3^-） content in out-flowing pulmonary plasma （OPP）. The degree of fibrosis in lung was evaluated by the content of hydroxyproline （chloramine T method） and area of collagen （Masson stain） in lung. The CTGF expression in lung was detected by Western blot and RT-PCR. The contents of NO2^-/NO3^- were increased in OPP of rats on day 14 after the instillation of BLM, compared with those in the rats with instillation of NS [（156±21） μmol/L vs （51±15） μmol/L, P〈0.01]. The content of hydroxyproline, the area of collagen, and the levels of CTGF protein and mRNA were increased in lungs of rats on day 30 after intratracheal instillation of BLM, compared with those in the rats with instillation of NS [hydroxyproline, （51 ± 10） mg/g lung vs （20±5） mg/g lung; area of collagen, （38.7±8.8）% vs （5.7± 1.5）%; CTGF protein, （1±0.25） vs （0.3±0.1）; CTGF mRNA, （0.8±0.2） vs （0.15±0.03）, P〈0.01]. The above-mentioned indices were ameliorated by the inhalation of AG （10 or 50 mmol/L） （NO2^-/NO3^- content, P〈0.01; other indices, P〈0.05）. It is therefore concluded that the inhalation of AG prevented the up-regulation of CTGF in fibrotic lungs of rats suffering from BLM instillation, which might be one of the mechanisms of the anti-fibrosis of AG in lungs.

关 键 词：氨基胍 诱导型一氧化氮合酶 结缔组织生长因子 博莱霉素 纤维化 肺 大鼠 

分 类 号：R563.9[医药卫生—呼吸系统]