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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 effect of ubiquitin-proteasome inhibitor MG-132 on pulmonary fibrosis in rats. Methods: 45 SD rats were randomly divided into control group, model group, intervention group and treatment group. The animal model of pulmonary fibrosis was established by intratracheal instillation of bleomycin (5mg.kg-1) in the model group and the intervention and treatment group. The control group was infused intratracheally with normal saline. In the intervention group, intraperitoneal injection (0.1 mg.kg-1.d-1) of MG-132 was given on the first day after modeling, and the model group and the control group were injected with the same amount of saline. In the treatment group, 28 MG-132 (0.1 mg.kg-1.d-1) was intraperitoneally injected. Lung coefficient, lung pathology and hydroxyproline (HYP) levels were measured at different time points. Results: The pulmonary coefficient and the content of HYP in lung tissue in intervention group and treatment group were lower than those in model group at each time point (P <0.01, P <0.05), and the degree of alveolitis was lighter than that in model group. Were significantly higher than the control group, but the intervention group and the treatment group 28d lung fibrosis lighter than the model group. Conclusion: Ubiquitin-proteasome inhibitor MG-132 has some effects on pulmonary fibrosis in rats.