过刊浏览

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

郭红, 陈晓玲, 陈超, 金辉, 李淑琴

河北医科大学1 基础医学研究所病理生理研究室；药学院药理研究室；临床学院实验中心，石家庄 050017

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 tissue growth 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 (2 mmol/L、10 mmol/L 或50 mmol/L，5 min/ 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10 mmol/L 和50 mmol/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。

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：R363

[Inhalation of aminoguanidine prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats.] [Ariticle in Chinese]

GUO Hong, CHEN Xiao-Ling, CHEN Chao, JIN Hui, LI Shu-Qin

Department of Pathophysiology, Institute of Basic Medical Science； Department of Pharmacology, College of Pharmaceutical Science； Experimental Center, Clinic College, Hebei Medical University, Shijiazhuang 050017, China

Abstract

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 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 mmol/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.

Key words: aminoguanidine; inducible nitric oxide synthase; connective tissue growth factor; bleomycin; fibrosis; lung; rat

收稿日期：2009-03-16　　录用日期：2009-05-20

通讯作者：陈晓玲　　E-mail: chen_xiaoling123@126.com

引用本文：

郭红, 陈晓玲, 陈超, 金辉, 李淑琴. 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[J]. 生理学报 2009; 61 (4): 361-366.

GUO Hong, CHEN Xiao-Ling, CHEN Chao, JIN Hui, LI Shu-Qin. [Inhalation of aminoguanidine prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (4): 361-366 (in Chinese with English abstract).