A phosphatidylinositol 3-kinase inhibitor strongly suppressed pulmonary vascular remodeling of allergic vasculitis in a murine model
A phosphatidylinositol 3-kinase inhibitor strongly suppressed pulmonary vascular remodeling of allergic vasculitis in a murine model
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DOI：
10.3109/01902148.2016.1157226
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发表时间：
2016-04-01
影响因子：
1.7
通讯作者：
Yamauchi, Kohei
中科院分区：
文献类型：
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作者：
Oikawa, Yuka;Sasaki, Nobuhito;Yamauchi, Kohei
目的：利用嗜酸性粒细胞浸润的变应性血管炎小鼠模型，研究泛I类PI3K抑制剂ZSTK474对血管重构的影响。方法：用OVA致敏C57BL/6小鼠。阳性对照每天暴露于雾化虫卵7天。另一组小鼠在雾化OVA的同时给予ZSTK474 (30mg/kg, p.o. / d)，连续7天。第3天和第7天分别行支气管肺泡灌洗（BAL），并切除肺进行病理分析。测定细胞差异，测定BAL液中IL-4、IL-5、IL-13和tgf - β的浓度。结果：暴露于OVA后第3天和第7天，zstk474处理组大鼠BALF细胞总数和嗜酸性粒细胞数量均显著降低。暴露于OVA后第3天和第7天，zstk474处理组外周血白细胞总数和嗜酸性粒细胞数量显著降低。zstk474处理组BAL液中IL-4、IL-5、IL-13的浓度也在第3天显著降低。zstk474处理组BAL液中tgf - β的浓度在第3天和第7天也显著降低。与对照组相比，zstk474治疗组病理评分明显降低。结论：PI3K抑制剂ZSTK474对嗜酸性粒细胞浸润的变应性血管炎小鼠模型肺血管重构有抑制作用。PI3K信号转导可能在过敏性血管炎的免疫过程中起关键作用。
Objectives: We investigated the effects of pan-class I PI3K inhibitor, ZSTK474 on vascular remodeling using a murine model of allergic vasculitis with eosinophil infiltration. Methods: C57BL/6 mice were sensitized with OVA. The positive controls were exposed to aerosolized OVA daily for 7days. The other group of mice were administered ZSTK474 (30mg/kg, p.o. daily) in parallel with daily exposure to aerosolized OVA for 7days. On the 3rd and 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of IL-4, IL-5, IL-13 and TGF-beta in BAL fluid were measured. Results: The total cell numbers and eosinophil numbers in BALF were greatly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The numbers of total white blood cells and eosinophils in the peripheral blood were significantly reduced in the ZSTK474-treated group on the 3rd and 7th day after exposure to OVA. The concentrations of IL-4, IL-5, and IL-13 in BAL fluids were also reduced significantly on the 3rd day in the ZSTK474-treated group. The concentrations of TGF-beta in BAL fluids were also reduced significantly on the 3rd and 7th day in the ZSTK474-treated group. The pathological scores reduced significantly in the ZSTK474-treated group compared to the control group. Conclusion: The PI3K inhibitor, ZSTK474 suppressed pulmonary vascular remodeling in the murine model of allergic vasculitis with eosinophil infiltration. PI3K signal transduction may have a critical role in the immunological process that induces allergic vasculitis.