合并酸误吸的特发性肺纤维化大鼠抑酸治疗研究
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摘要
目的探讨抑酸治疗对合并酸误吸的特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)大鼠病情发展及转归的影响。方法 36只雄性SD大鼠随机分为正常对照组10只、模型组6只、抑酸组10只和糖皮质激素组10只。模型组、抑酸组和糖皮质激素组大鼠经鼻滴入博来霉素(7μg/g)建立IPF模型,对照组经鼻滴入生理盐水;建模后28 d,抑酸组和糖皮质激素组大鼠雾化吸入稀盐酸建立酸误吸模型,并分别给予盐酸雷尼替丁、醋酸泼尼松灌胃治疗28 d;对照组和模型组给予生理盐水雾化吸入和灌胃。治疗28 d后,观察4组大鼠肺组织病理改变,并检测pa(O_2)及血清丙二醛(malondialdehyde, MDA)水平。结果抑酸组和糖皮质激素组治疗28 d后肺组织病理炎症细胞及成纤维细胞较模型组减少;治疗28 d后对照组大鼠血清MDA水平[(6.820±0.470)nmol/L]低于模型组[(16.040±1.680)nmol/L]、抑酸组[(11.860±2.550)nmol/L]和糖皮质激素组[(10.310±3.230)nmol/L](P<0.05),抑酸组和糖皮质激素组低于模型组(P<0.05),抑酸组与糖皮质激素组比较差异无统计学意义(P>0.05);pa(O_2)对照组[(11.594±1.016)kPa]、模型组[(11.037±0.552)kPa]、抑酸组[(11.390±0.788)kPa]及糖皮质激素组[(11.247±1.002)kPa]两两比较差异均无统计学意义(P>0.05)。结论抑酸治疗一定程度上可减轻合并酸误吸的IPF大鼠肺泡炎症及肺纤维化程度。
Objective To explore the influence of acid suppression therapy on the development and prognosis of idiopathic pulmonary fibrosis(IPF) in rats with acid aspiration. Methods Thirty-six SD male rats were randomly divided into normal control group(n=10), model group(n=6), acid suppression group(n=10) and glucocorticoid group(n=10). The IPF model was established by intranasal drip of bleomycin(7 μg/g) in model group, acid suppression group and glucocorticoid group, while normal saline was intranasally dripped in control group. By day 28 after modeling, acid aspiration model was established by inhaling dilute hydrochloric acid by atomization in acid suppression group and glucocorticoid group, followed by 28-day lavage with ranitidine hydrochloride and prednisone acetate. Normal saline was used for atomization and lavage in both control group and model group. After 28-day treatment, the histopathological changes of lung tissues were observed, and the levels of pa(O_2) and malondialdehyde were measured. Results After 28-day treatment, inflammatory cells and fibroblasts were less in acid suppression group and glucocorticoid group than those in model group. The serum malondialdehyde level was significantly lower in control group((6.820±0.470) nmol/L) than that in model group((16.040±1.680) nmol/L), acid suppression group((11.860±2.550) nmol/L) and glucocorticoid group((10.310±3.230) nmol/L)(P<0.05), lower in acid suppression group and glucocorticoid group than that in model group(P<0.05), and showed no significant difference between acid suppression group and glucocorticoid group(P>0.05). No significant difference was found in multiple comparison in the level of pa(O_2) among control group((11.594±1.016) kPa), model group((11.037±0.552) kPa), acid suppression group((11.390±0.788) kPa) and glucocorticoid group((11.247±1.002) kPa)(P>0.05). Conclusion Acid suppression therapy can alleviate the degree of alveolar inflammation and pulmonary fibrosis in IPF rats complicated with acid aspiration.
Objective To explore the influence of acid suppression therapy on the development and prognosis of idiopathic pulmonary fibrosis(IPF) in rats with acid aspiration. Methods Thirty-six SD male rats were randomly divided into normal control group(n=10), model group(n=6), acid suppression group(n=10) and glucocorticoid group(n=10). The IPF model was established by intranasal drip of bleomycin(7 μg/g) in model group, acid suppression group and glucocorticoid group, while normal saline was intranasally dripped in control group. By day 28 after modeling, acid aspiration model was established by inhaling dilute hydrochloric acid by atomization in acid suppression group and glucocorticoid group, followed by 28-day lavage with ranitidine hydrochloride and prednisone acetate. Normal saline was used for atomization and lavage in both control group and model group. After 28-day treatment, the histopathological changes of lung tissues were observed, and the levels of pa(O_2) and malondialdehyde were measured. Results After 28-day treatment, inflammatory cells and fibroblasts were less in acid suppression group and glucocorticoid group than those in model group. The serum malondialdehyde level was significantly lower in control group((6.820±0.470) nmol/L) than that in model group((16.040±1.680) nmol/L), acid suppression group((11.860±2.550) nmol/L) and glucocorticoid group((10.310±3.230) nmol/L)(P<0.05), lower in acid suppression group and glucocorticoid group than that in model group(P<0.05), and showed no significant difference between acid suppression group and glucocorticoid group(P>0.05). No significant difference was found in multiple comparison in the level of pa(O_2) among control group((11.594±1.016) kPa), model group((11.037±0.552) kPa), acid suppression group((11.390±0.788) kPa) and glucocorticoid group((11.247±1.002) kPa)(P>0.05). Conclusion Acid suppression therapy can alleviate the degree of alveolar inflammation and pulmonary fibrosis in IPF rats complicated with acid aspiration.
引文
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[9] 中华医学会呼吸病学分会间质性肺疾病学组.特发性肺纤维化诊断和治疗中国专家共识[J].中华结核和呼吸杂志,2016,39(6):427-432.
[10] KILLIC T, PARLAKPINAR H, POLAT A, et al. Protective and therapeutic effect of molsidomine on bleomycin-induced lung fibrosis in rats[J]. Inflammation,2014,37(4):1-15.
[2] 齐军,尚圣云,李振华,等.特发性肺纤维化与胃食管反流的相关性研究[J].中华内科杂志,2015,54(8):695-698.
[3] 陈碧,蒋捍东.胃食管反流病与特发性肺纤维化[J].中华结核和呼吸杂志,2016,39(2):137-139.
[4] LEE J S, COLLARD H R, ANSTROM K J, et al. Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomized controlled trials[J]. Lancet Respir Med,2013,1(5):369-376.
[5] 邱元胜,闫仁淑.布地奈德雾化吸入干预博莱霉素致大鼠肺纤维化实验研究[J].中华实用诊断与治疗杂志,2012,26(11):1086-1088,1091.
[6] 李飞,于洪涛,朱明慧,等.特发性肺纤维化患者发生肺动脉高压的危险因素分析[J].中华实用诊断与治疗杂志,2018,32(11):1096-1099.
[7] 贺琛,俞小卫.特发性肺纤维化的治疗与进展[J].临床肺科杂志,2015,20(10):1890-1892.
[8] 耿艳艳,周植星,胡倩倩,等.特发性肺纤维化治疗靶点及药物研究进展[J].中国新药杂志,2015,24(1):46-51.
[9] 中华医学会呼吸病学分会间质性肺疾病学组.特发性肺纤维化诊断和治疗中国专家共识[J].中华结核和呼吸杂志,2016,39(6):427-432.
[10] KILLIC T, PARLAKPINAR H, POLAT A, et al. Protective and therapeutic effect of molsidomine on bleomycin-induced lung fibrosis in rats[J]. Inflammation,2014,37(4):1-15.