实验性酸吸入与大鼠肺纤维化相关性研究  

Study about correlation of experimental acid inhalation and pulmonary fibrosis in rats

作　　者：陈石[1] 张德平[2] 

机构地区：[1]南京市胸科医院呼吸科二区,210029 [2]南京市鼓楼医院呼吸科,210008

出　　处：《国际呼吸杂志》2010年第14期845-850,F0003,共7页International Journal of Respiration

基　　金：基金项目：江苏省医学135重点人才资助项目（RC2001005）

摘　　要：目的 研究实验性酸吸入与大鼠肺间质纤维化的相关性及其可能的作用机制并与传统的博莱霉素致纤维化作一比较.方法 健康雄性SD大鼠120只,随机分为正常对照组（N组）、博莱霉素组（B组）、高浓度盐酸组、中浓度盐酸组和低浓度盐酸组,每组24只.B组气管内一次性注入博莱霉素诱导纤维化,盐酸组每周气管内滴注不同浓度盐酸1次,N组每周气管内滴注生理盐水1次.各组分别于造模后第7、14、28及42天随机处死6只,取肺组织行HE、Masson染色评价肺组织病理变化,用逆转录-聚合酶链式反应方法测定肺组织转化生长因子β1的mRNA表达,用免疫组织化学方法半定量测定Ⅰ型胶原蛋白、结缔组织生长因子的表达.结果 盐酸组肺泡炎程度始终显著高于N组（P〈0.01）,在开始2周内达到高峰,随后仍旧维持一个相对较高状态,从28 d达到或者超过B组水平.盐酸组纤维化程度随时间逐渐增强,高于N组（P〈0.05或P〈0.01）,但始终未超过B组.盐酸组肺组织转化生长因子β1mRNA在28 d时达到B组水平,至42 d时全面超过B组水平.B组大鼠各时间点肺组织Ⅰ型胶原表达均高于N组及3个盐酸组（P〈0.05）.高、中浓度盐酸组结缔组织生长因子表达从14 d起高于N组（P〈0.05）,且随滴注次数及时间增加而增强.结论 本实验从一个角度反映了经常性胃食管酸反流引起的酸吸入与肺纤维化的相关性,为揭示胃食管反流病与特发性肺纤维化的关系提供了初步的实验室证据.Objective To study the correlation of experimental acid inhalation and pulmonary fibrosis in rats and possible mechanism, and make a comparison with traditional bleomycin-induced fibrosis. Methods 120 healthy male SD rats were randomly divided into normal control group, bleomycin group,high-concentration hydrochloric acid group,middle-concentration hydrochloric acid group,and low-concentration hydrochloric acid group, 24 rats in each group. The rats in bleomycin group were intratracheally injected with bleomycin once to induce pulmonary fibrosis. The rats in hydrochloric acid groups were intratracheally dripped with different concentrations of hydrochloric acid once per week. The rats in normal control group were intratracheally dripped with saline once per week. Six rats of each group were randomly sacrificed on the 7th, 14th,28th and 42th day respectively. HE and Masson staining were used to evaluate the pathological changes of lung tissues. Reverse transcription-polymerase chain reaction was used to detect mRNA expression of transforming growth factor-β1. The expressions of type Ⅰ collagen and connective tissue growth factor were semi-quantitatively determinated by immunohistochemical method. Results The alveolitis level in hydrochloric acid groups was higher than that in normal control group （P〈0. 01）,reached a peak at two weeks,and then still maintained a relatively high status,reached or exceeded that in bleomycin group at the 28th day. The fibrosis level in hydrochloric acid groups gradually increased, was higher than that in normal control group （P〈0. 05 or P 〈0. 01） ,but was not more than that in bleomycin group. The mRNA level of transforming growth factor-pi in lung tissues of hydrochloric acid group reached that in bleomycin group at the 28th day,and exceeded that in bleomycin group at the 42th day. The expression of type Ⅰ collagen in lung tissues of bleomycin group was higher than that in normal control group and hydrochloric acid groups at all time points （P〈0. 05）. The exp

关 键 词：肺纤维化 胃食管反流病 盐酸 博莱霉素 

分 类 号：R285.5[医药卫生—中药学]