26S蛋白酶体在博来霉素诱导大鼠肺纤维化中的作用研究  

Effect of 26S proteasome on bleomycin-induced pulmonary fibrosis in rats

作　　者：袁殷茹 张敏 YUAN Yin-ru;ZHANG Min(Department of Respiratory Medicine,Guangzhou Red Cross Hospital,Medical College,Jinan University,Guangzhou 510220,Guangdong Province,China)

机构地区：[1]广州市红十字会医院/暨南大学医学院附属广州红十字会医院呼吸内科

出　　处：《中国临床药理学杂志》2019年第20期2555-2558,2562,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81100042)

摘　　要：目的 探讨26S蛋白酶体在博来霉素诱导的大鼠肺纤维化形成中的作用。方法 42只SD大鼠随机分为对照组6只、模型组18只和实验组18只。模型组和实验组大鼠从气管内滴入10 mg·kg^-1博来霉素建立肺纤维化动物模型。实验组自造模当日开始,腹腔注射0. 1 mg·kg^-1MG132,qd,直至处死前1 d。对照组和模型组均给予腹腔注射等体积0. 9%NaCl。对照组于造模后第7天处死,模型组和实验组于造模后第7,14和28天分批处死。用HE染色和Masson染色观察肺组织炎症及纤维化情况,用Western Blot法检测Ⅰ型胶原α1(COL1A1)的表达,用酶联免疫吸附实验法检测肺组织20S蛋白酶体活性的表达情况。结果 对照组、模型组(第7,14和28天)和实验组(第7,14和28天)的肺泡炎评分分别为(0. 50±0. 58),(2. 21±0. 84),(2. 42±0. 55),(2. 60±0. 55),(2. 19±0. 55),(2. 22±0. 71)和(1. 43±0. 55)分,肺纤维化评分分别为(0. 25±0. 50),(2. 01±0. 71),(2. 22±0. 44),(2. 42±0. 55),(2. 09±0. 55),(2. 02±0. 45)和(1. 51±0. 55)分,模型组各时间点的上述指标与对照组比较,差异均有统计学意义(均P <0. 05),实验组第28天的上述指标与同时期模型组比较,差异均有统计学意义(均P <0. 05)。对照组、模型组(第7,14和28天)和实验组(第7,14和28天)的COL1A1蛋白表达量分别为(0. 29±0. 02),(0. 69±0. 04),(0. 77±0. 04),(0. 93±0. 11),(0. 67±0. 01),(0. 62±0. 03)和(0. 52±0. 03),模型各组与对照组比较,差异均有统计学意义(均P <0. 05),实验组第14和28天与同时期模型组比较差异均有统计学意义(均P <0. 05)。对照组、模型组(第7,14和28天)和实验组(第7,14和28天)的肺组织20S蛋白酶体活性分别为(98. 69±6. 98),(300. 55±31. 85),(438. 57±77. 96),(450. 27±94. 99),(172. 65±61. 79),(281. 64±57. 79),(204. 64±33. 96);模型各组与对照组比较差异均有统计学意义(均P <0. 05),各时间点的实验组与同时期模型组比较差异均有统计学意义(均P <0. 05)。�Objective To investigate the effect of 26 S proteasome on bleomycin-induced pulmonary fibrosis in rats and to explore the possible molecular mechanism.Methods SD rats were randomly divided into three groups:control,model and experimental groups.The model and experimental groups were intratracheally instilled with bleomycin(10 mg·kg^-1),and the control group was subjected to equivalent saline.The rats of experimental groups were intraperitoneal injection of MG132(0.1 mg·kg^-1·d^-1)daily until the day before execution.The rats of model and experimental groups were sacrificed on the 7 th,14 th and 28 th experiment day.HE and Masson staining were used to observe pulmonary alveolitis and lung fibrosis.The expression levels of collagen typeⅠalpha 1(COL1A1)was detected by Western blotting method.The expression levels of 26S and 20S proteasome,and the activity of 20S proteasome were detected by enzyme-linked immunosorbent assay.Results The scores of pulmonary alveolitis of control,model(d7,d14,d28)and experimental(d7,d14,d28)groups were(0.50±0.58),(2.21±0.84),(2.42±0.55),(2.60±0.55),(2.19±0.55),(2.22±0.71)and(1.43±0.55),the scores of lung fibrosis were(0.25±0.50),(2.01±0.71),(2.22±0.44),(2.42±0.55),(2.09±0.55),(2.02±0.45)and(1.51±0.55),the differences of above factors between control and model groups at different time were statistically significant(all P<0.05),and the difference between experimental and model groups on the 28 th experiment day were statistically significant(P<0.05).The expression levels of COL1A1 protein of control,model(d7,d14,d28)and experimental(d7,d14,d28)groups were(0.29±0.02),(0.69±0.04),(0.77±0.04),(0.93±0.11),(0.67±0.01),(0.62±0.03)and(0.52±0.03),the differences between control and model groups were statistically significant(all P<0.05),and the differences between experimental and model groups on the 14 th and 28 th experiment day were statistically significant(all P<0.05).The activity of 20S proteasome of control,model(d7,d14,d28)and experimental(d7,d14,d28)groups were(

关 键 词：肺纤维化 泛素-蛋白酶体通路 26S蛋白酶体 MG132 

分 类 号：R97[医药卫生—药品]