| 摘要: |
| 目的探讨血管内皮生长因子（VEGF）受体抑制剂Z-3-[（2，4-二甲基吡咯-5-烃基）亚甲基]-2-吲哚满酮（SU5416）对脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）后肺纤维化的影响。方法90只雄性C57BL/6小鼠随机分为LPS模型组（MG组）、SU5416干预组（TG组）和正常对照组（CG组），每组30只。MG组及TG组小鼠经尾静脉注射0.5mlLPS（5mg/kg）建立小鼠ALI模型；CG组以等体积0.9%氯化钠注射液代替。30min后，TG组小鼠即予腹腔注射0.5mlSU5416（50mg/kg），MG组和CG组小鼠则腹腔注射等体积0.9%氯化钠注射液。于第7、14、28天分别处死3组小鼠各10只；行HE及Masson染色观察小鼠肺损伤改变；检测肺组织匀浆中羟脯氨酸水平；免疫组化法测定肺组织VEGF、CD31表达水平。结果MG组小鼠第7天肺损伤明显，肺呈纤维化改变，第28天纤维化进一步加重；同一时间点，MG组及TG组小鼠肺损伤评分、羟脯氨酸水平、CD31及VEGF表达水平均高于对照组（均P＜0.05），而TG组小鼠上述指标均低于MG组（均P＜0.05）。结论SU5416可减轻LPS诱导小鼠ALI后肺纤维化，其可能通过抑制VEGF、CD31表达发挥作用。 |
| 关键词: 血管内皮生长因子受体抑制剂 急性肺损伤 肺纤维化 VEGF CD31 |
| DOI：10.12056/j.issn.1006-2785.2017.39.02.2016-1484 |
| 分类号: |
| 基金项目:浙江省公益性技术应用研究计划项目（2015C33258）；杭州市社会发展自主申报项目（20160533B18）；杭州市卫生科技计划项目（2011A017） |
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| VEGF receptor inhibitor SU5416 attenuates pulmonary fibrosis in mice with acute lung injury |
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HUANG Xuqing, XU Changqing, TONG Yueyang
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the Affiliated Hospital of Hangzhou Normal University
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| Abstract: |
| Objective To investigate the effect of VEGF receptor inhibitor SU5416 on pulmonary fibrosis after acute lung injury in rats. Methods Ninety C57BL/6 mice were randomly divided into three groups (n=30 in each group). Lung injury was induced by injection of lipopolysaccharide (LPS) via caudal vein in model group and intervention group; mice in control group were injected with 0.5ml normal saline instead. SU5416 (50mg/kg) was given to mice in intervention group and the same volume of normal saline was given to mice in control group and model group. Mice were sacrificed at d7, d14 and d28. Pathological changes of the lung tissue and ALI score and hydroxyprolline contents were examined. The expression of VEGF and CD31 were measured by immunohistochemistry. Results ALI score, the expression of VEGF and CD31, and hydroxyprolline contents in model group and intervention group were higher than those in control group. Compared with model group, these changes were attenuated significantly in intervention group. Conclusion Administration of SU5416 can attenuate LPS-induced pulmonary fibrosis in mice, which is associated with the down-regulation of VEGF and CD31 expression. |
| Key words: Vascular endothelial growth factor receptor inhibitor Acute lung injury Pulmonary fibrosis VEGF CD31 |
