柴胡皂甙d干预肺纤维化VEGF/PEDF表达的实验研究

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。

The Effect of Saikosapoin-d Intervention on VEGF/PEDF Expression in Experimental Pulmonary Fibrosis in Mice

Objective: To investigate the effect of saikosapoin-d (SSd) on the expression of vascular endothelial growth factor (VEGF)/pigment epithelium-derived factor (PEDF) in lung tissue at different times, and to explore its relationship with anti-fibrosis in mice. Methods: Eighty mice were randomly divided into four groups: control group , model group (bleomycin, BLM) and two treatment groups (P< 0.01). Mice in treatment groups were injected intraperitoneally with SSd at different doses (2.0 mg/kg and 1.0 mg/kg) once per day. Samples of lung tissue were stained with Masson method. Hydroxyproline (HYP) content was evaluated. The expressive levels of VEGF and PEDF mRNA were observed by immunofluorescence. The expressive intensity of VEGF and PEDF mRNA was detected by RT-PCR at the 3 th , 7 th , 14 th and 28 th day. Results: In model group and SSd treatment groups, fibrosis was found gradually progressed, which was minor on 28 th day in SSd treatment group than that of BLM group (P<0.01). HYP levels increased gradually in BLM group and SSd group. HYP contents were lower on the 7 th , 14 th and 28 th day in SSd treatment group than those of BLM group (P<0.001). The expression of VEGF increased from the third day and reached the peak on the 7 th day in BLM group and SSd group. Then the expression of VEGF gradually decreased and reached the lowest level at 28 th day. The expression of PEDF presented tendency of elevation gradually. In treatment groups , the expression of VEGF was lower than that in model group. The expression of PEDF mRNA was higher in SSd group than that in model group (P<0.05 or P<0.01). Conclusion: SSd can inhibit pulmonary fibrosis in mice, which may be related to the down-regulation of VEGF and up-regulation of PEDF.