泛素-蛋白酶体抑制剂对大鼠肺纤维化的影响

Effects of ubiquitin-proteasome inhibitor MG-132 on bleomycin induced pulmonary fibrosis in rats

目的:探讨泛素-蛋白酶体抑制剂MG-132对大鼠肺纤维化的影响。方法:45只SD大鼠随机分成对照组、模型组、干预组和治疗组。模型组和干预、治疗组大鼠气管内滴入博来霉素(5mg.kg-1)建立肺纤维化动物模型,对照组以等量生理盐水气管内滴入。干预组于第造模后第1天起给予MG-132腹腔内注射(0.1mg.kg-1.d-1),模型组和对照组注射等量生理盐水;治疗组于造模后第28天起给予MG-132(0.1mg.kg-1.d-1)腹腔内注射。于不同时间点测肺系数、肺组织行病理学检查及肺组织羟脯氨酸(HYP)含量测定。结果:干预组及治疗组肺系数及肺组织HYP含量各时间点均低于模型组(P<0.01,P<0.05),肺泡炎的程度也轻于模型组;虽然干预组和治疗组肺纤维化程度均明显重于对照组,但干预组28d和治疗组肺纤维化较模型组轻。结论:泛素-蛋白酶体抑制剂MG-132对大鼠肺纤维化有一定的干预、治疗作用。

OBJECTIVE To investigate the effects of ubiquitin-proteasome inhibitor MG-132 on pulmonary fibrosis in rats. METHODS 45 male SD rats were randomly divided into four groups~ control group, model group, intervention group and treatment group. The model group, intervention group and treatment group were intratracheally instilled with bleomycin （5 mg·kg 1）, the control group were subjected to equivalent saline. The intervention group were intraperitoneally injected with MG- 132 （0. 1 mg·kg-1· d-1 ） from the first day after intratraeheal instillation, the model group and control group were intraperitoneally injected with equivalent saline. The treatment group were intraperitoneally injected with MG-132 （0. 1 mg· kg-1·d l ） from 28th day after intratracheal instillation. The lung coefficient, lung pathological manifestations and level of hydroxyproline （HYP） in lung tissue were evaluated at different time points in each group, RESULTS The lung coefficient and level of HYP and in intervention group and treatment group were all lower than those of model group significantly（P〈0. 01, P〈0, 05）, also the same of degree of alveolitis;although the degree of lung fibrosis in intervention group and model group and treatment group were all more severe than those of control group,whereas the degree of lung fibrosis in intervention group at 28th day and treatment group were lessened compared with those of model group, CONCLUSION Ubiquitin-proteasome inhibitor MG-132 can prevent and reduce pulmonary fibrosis to some degree in rats.