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目的研究阿奇霉素脂质体对博来霉素诱导大鼠肺纤维化的保护作用。方法 SD大鼠72只,随机分为空白对照组(n=6)、模型组(n=18)、溶液组(n=24)和脂质体组(n=24),后3组一次性向大鼠气管内注入博来霉素5 mg.kg-1制成肺间质纤维化模型,分别每日尾静脉注射给予生理盐水、阿奇霉素溶液(2.50 g.L-1)和阿奇霉素脂质体(2.61 g.L-1),连续28 d,各组分别于d 7、d 14、d 28和停药后d 28(d 56)处死。各组动物处死后测量肺重系数,测定肺组织匀浆内丙二醛(MDA)、羟脯氨酸(HP)含量,提取肺组织进行HE、Masson染色并进行病理半定量分析。结果博来霉素诱导大鼠肺重系数增加,MDA和HP含量增高、肺泡炎和肺纤维化显著,与空白对照组相比有非常显著差异(P<0.01)。d 7、d 14、d 28溶液组和脂质体组与同时点模型组相比肺重系数、MDA和HP含量均显著降低(P<0.05),脂质体组肺泡炎程度于不同时点均减轻(P<0.05)。脂质体组d 56与d 28相比无明显反弹(P>0.05),而溶液组出现反弹(P<0.05)。结论阿奇霉素脂质体能够有效地治疗病变过程中的肺泡炎,对纤维化有明显的防治作用,停药后能持续有效地发挥作用。
Objective To study the protective effect of azithromycin liposomes on bleomycin-induced pulmonary fibrosis in rats. Methods Totally 72 SD rats were randomly divided into blank control group (n = 6), model group (n = 18), solution group (n = 24) and liposome group Rats were injected bleomycin 5 mg.kg-1 intratracheally to establish pulmonary interstitial fibrosis model. The rats were injected intravenously with saline, azithromycin solution (2.50 gL-1) and azithromycin liposome (2.61 gL -1) for 28 consecutive days. All rats were killed on d 7, d 14, d 28 and d 28 (d 56) after stopping. Lung weights were measured after sacrifice in each group. Malondialdehyde (MDA) and hydroxyproline (HP) contents were measured in lung homogenates. HE and Masson stainings were performed for lung tissue samples and semi-quantitative histopathological analysis was performed. Results Bleomycin induced a significant increase in lung weight index, MDA and HP content, alveolitis and pulmonary fibrosis in rats compared with the control group (P <0.01). Compared with the model group at the same time point, the lung weight coefficient, the content of MDA and HP in d 7, d 14, d 28 solution group and the liposome group were significantly decreased (P <0.05), the degree of alveolitis in the liposome group at different time points (P <0.05). Compared with d 28, d 56 did not significantly rebound in the liposome group (P> 0.05), while the solution group rebounded (P <0.05). Conclusion Azithromycin liposomes can effectively treat alveolitis in the course of the disease, and have obvious preventive and therapeutic effects on fibrosis, and can effectively and continuously exert its effect after stopping the drug treatment.