酸吸入致大鼠肺纤维化初步探索

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机制并与博来霉素致纤维化比较。方法雄性SD大鼠120只，随机分为正常对照组、博来霉素组、高浓度盐酸组、中浓度盐酸组和低浓度盐酸组，每组24只。博来霉素组气管内一次性注入博来霉素诱导纤维化，盐酸组每周气管内滴注不同浓度盐酸1次，正常对照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RT-PCR方法测定肺组织转化生长因子β1（TGF—β1）的mRNA表达，用免疫组化的方法半定量测定结缔组织生长因子（CTGF）的表达。结果盐酸组肺泡炎程度始终显著高于对照组（P〈0．01），28d达到或者超过博来霉素组水平。盐酸组纤维化程度随时间逐渐增强，显著高于对照组沪〈0．01或0．05），但始终未超过博来霉素组（P〉0．05）。盐酸组肺组织的TGFβ1 mRNA在28d时达到博来霉素组水平，至42d时全面超过博来霉素组水平。高、中浓度盐酸组CTGF表达高于正常阴性对照组（P〈0．05），且随滴注次数增加及时间延长而增强。结论本实验反映经常性胃食管酸反流引起的酸吸入与肺纤维化相关。

Correlation of Experimental Acid Aspiration and Pulmonary Fibrosis in Rats

Objective To study the pathology and possible mechanism of pulmonary fibrosis in rats induced by experimental hydrochloric acid （HCl） inhalation and compared with traditional bleomycin- induced fibrosis. Method One-hundred and twenty male SD rats were randomly divided into nomal control, bleomycin, high, middle and low-dose HCl group.The bleomycin group was intratracheally injected bleomycin, the HCl groups were intratracheally injected HCl once per week, and the control group was given saline in the same way.Six rats of each group were randomly sacrificed on day 7, 14, 28 and 42 respectively.The histological changes of the lung tissue were evaluated by HE and Masson＇s trichrome staining. The mRNA expression of transforming growth factor-β1（TGF-β1） were assayed by RT-PCR. The CTGF expression were analyzed by immunohistochemistry. Results Hydrochloride groups has significantly higher alveolitis levels （P〈0.0 1） and can reach or exceed the level of bleomycin group after 28d. Fibrosis in hydrochloric acid groups were increased gradually over time, but not consistently exceeded bleomycin group （P〉0.05）. Similar results appear in the TGF-[31 mRNA and CTGF expression in immunohistochemical identification. Conclusion The results revealed the relationship between the gastroesophageal reflux disease （GERD） and idiopathic pulmonary fibrosis （IPF）.