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柴胡皂甙d干预肺纤维化VEGF/PEDF表达的实验研究

郑金旭1,许清2   

  1. 1. 江苏大学附属江滨医院呼吸科
    2. 江苏大学附属江滨医院呼吸内科
  • 收稿日期:2011-12-29 修回日期:2012-03-25 出版日期:2012-08-15 发布日期:2012-08-15
  • 通讯作者: 郑金旭

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  • Received:2011-12-29 Revised:2012-03-25 Published:2012-08-15 Online:2012-08-15

摘要: 摘要 目的 观察柴胡皂甙d(saikosaponin-d SSd)对博来霉素(BLM)致肺纤维化小鼠肺组织血管内皮生长因子(VEGF)/色素上皮衍生因子(PEDF)在不同时间表达变化的调节作用,并探讨其与抗肺纤维化作用的关系。 方法 将80只小鼠随机分为4组,正常对照组,模型组,SSd大、小剂量治疗组。治疗组分别每天腹腔注射不同剂量SSd, MASSON染色观察纤维化程度,样本碱水解法检测肺组织中羟脯氨酸(HYP)含量,免疫荧光观察PEDF、VEGF蛋白在肺内表达的规律,RT-PCR观察各时间点PEDF、VEGF mRNA表达的强度。 结果 MASSON染色示模型组、治疗组均纤维化逐渐进展的动态变化;HYP含量随时间逐渐增加;造模组VEGF表达从第三天开始升高,第7天达高峰,之后逐渐下降,28天到最低,PEDF表达总体呈现逐渐增高趋势;治疗组VEGF表达总体比单纯造模组降低,并呈剂量依赖关系;PEDF表达比造模组升高,呈剂量依赖关系;结论 SSd能够抑制肺纤维化进展,机制可能与下调VEGF的表达,上调PEDF的表达有关。

关键词: 柴胡皂甙d, 肺纤维化, 血管内皮生长因子, 色素上皮衍生因子, 小鼠

Abstract: Abstract Objective:To investigate the effect of saikosapoin-d(SSd)on the expression of VEGF/PEDF at different times in lung tissue of Blemycin-induced pulmonary fibrosis in mice,and to explore its relationship with anti-fibrosis. Methods:Eighty mice were randomly divided into four groups: control group,model group and two treatment groups.After modeling,the Mice in the treatment groups were injected intraperitoneally with SSd at different doses once per day.Lung tissue was stained with Masson method,Hydroxyproline(HYP) content was evaluated,the expressive law of VEGF and PEDF was observed by immunofluorescence, the expressive intensity of VEGF and PEDF mRNA was dectected by RT-PCR. Results:In model group and treatment groups, dynamic changes from alveolitis to pulmonary fibrosis could be observed in Masson staining; HYP levels increased gradually,and reached peak on the day of 28.The expression of VEGF in model group began to increase from the third day,reached the peak on the seventh day,then gradually decreased;the expression of PEDF presented tendency which elevates gradually.In treatment groups,the expression of VEGF was lower than in model group;the expression of PEDF mRNA in 2 SSd groups was higher than in model group. Conclusion:SSd can inhibit pulmonary fibrosis in mice, it may be related to the down-regulation of VEGF and up-regulation of PEDF, and this effect is positively related to dose.

Key words: SSd, Pulmonary fibrosis, VEGF, PEDF, Mice