PI3K/Akt信号介导血管生成参与口腔黏膜下纤维化形成的机制研究

Mechanism of PI3K/Akt Signal Mediating Angiogenesis in the Formation of Oral Submucosal Fibrosis

目的基于磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol-3-kinase/protein kinaseB,PI3K/Akt)信号探讨口腔黏膜下纤维化(oral submucous fibrosis,OSF)血管生成的机制。方法在C57BL/6J小鼠中建立OSF模型,分为对照组、OSF组、LY2940002组和OSF+LY2940002组,每组12只小鼠。免疫组织化学分析血管生成,苏木精-伊红(hematoxylin-eosin,HE)染色、VanGieson染色(VG染色)、Masson染色进行组织病理学分析,检测成纤维细胞迁移和侵袭能力,Westernblot检测PI3K/Akt的表达。结果与对照组相比,OSF组小鼠HE染色主要表现为口腔黏膜上皮萎缩;OSF组VG染色和Masson染色胶原蛋白较多。与对照组和OSF组中、晚期相比,OSF组小鼠早期口腔黏膜下的血管数量在增加。与对照组比较,OSF组小鼠的黏膜下组织血管数量增加(P<0.05);与OSF组比较,OSF+LY2940002组和LY2940002组小鼠血管数量减少(P均<0.05)。与对照组比较,OSF组小鼠的PI3K/Akt表达水平增加,成纤维细胞迁移和侵袭能力增加(P均<0.05);与OSF组比较,OSF+LY2940002组小鼠的PI3K/Akt的表达下调,抑制了OSF细胞的迁移和侵袭能力(P均<0.05)。结论PI3K/Akt信号可能促进OSF细胞的迁移和侵袭以及口腔黏膜血管生成。

Objective To investigate the mechanism of angiogenesis in oral submucous fibrosis(OSF)based on phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signal.Methods The OSF model was established among the C57BL/6J mice,which was divided into control group,OSF group,LY2940002 group and OSF+LY2940002 group,with 12 mice in each.Angiogenesis was analyzed by immunohistochemical;epidemiology of tissue was analyzed by hematoxylin-eosin(HE)staining,Van Gieson(VG)staining and Masson staining;migration and invasion abilities of fibroblasts were detected;the expression of PI3K/Akt was detected by Western blot.Results Compared with the control group,HE staining in OSF group mainly showed atrophy of oral mucosa epithelium;VG staining and Masson staining in the OSF group showed more collagen.Compared with the control group and OSF group in middle and late stage,early oral submucous vascular number of mice in OSF group increased.Compared with control group,the number of blood vessels in the submucosal tissue of mice increased in the OSF group(P<0.05);compared with OSF group,the number of blood vessels of mice in OSF+LY2940002 group and LY2940002 group decreased(all P<0.05).Compared with the mice in control group,the expression level of PI3K/Akt increased,migration and invasion ability of fibroblast in OSF group increased(all P<0.05);compared with OSF group,expression of PI3K/Akt of mice in OSF+LY2940002 group downregulated,the migration and invasion abilities of OSF cell were inhibited(all P<0.05).Conclusion PI3K/Akt signal may promote the migration and invasion of OSF cells as well as angiogenesis in the oral mucosa.