平滑肌细胞迁移在动静脉内瘘内膜增生中的作用机制研究

The Role and Regulating Mechanism of Smooth Muscle Cells in the Intimal Hyperplasia of Native AVF

目的:探讨平滑肌细胞迁移在自体动静脉内瘘(arteriovenous fistula,AVF)内膜增生中的作用及可能的调控机制。方法:标本选自因AVF狭窄或闭塞不能维持正常血液透析治疗,需再次手术的尿毒症患者,通过对AVF失功的静脉侧标本的研究,伊红染色观察血管组织形态学变化,测量各组内膜、中膜厚度;免疫组化观察血管病变中碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、胰岛素生长因子1(insulin-like growth factor,IGF-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达;Western blot检测金属基质蛋白酶2(matrix metallopro-teinase 2,MMP2)、金属基质蛋白酶9(matrix me-talloproteinase 9,MMP9)蛋白水平。结果:AVF流出道侧静脉内膜增生明显导致血管壁增厚,且内膜中可见大量平滑肌细胞及少量炎症细胞,静脉壁中bFGF、IGF-1表达水平明显升高,增生静脉的新生内膜层MMP2、MMP9表达增加,与对照组相比,失功的AVF标本MMP2表达水平显著增加,且差异具有统计学意义(P<0.05)。结论:内膜增生是AVF失功的主要原因,平滑肌细胞可通过中膜向内膜迁移并上调bFGF、IGF-1、MMP2细胞因子的表达以维持内膜的持续增生。

Objective:To study the role of the smooth muscle cells(SMCs)in the outflow venous intimal hyperplasia of native AVF and the possible regulating mechanism.Methods:The specimens from the patients suffered from dysfunction of AVF.Each group tissues were examined for histological changes after staining with HE and were measured thickness of intima and media.Immunohistochemical staining for basic fibroblast growth factor(bFGF),insulin-like growth factor 1(IGF-1)and vascular endothelial growth factor(VEGF).Western blot was used to observe the matrix metalloproteinase 2(MMP2)and matrix metalloproteinase-9(MMP9)expression.Results:The wall of outflow vein thickened obviously because of the intimal hyperplasia and plenty of SMCs and inflammatory cells were found in the venous intima of AVF.The expression levels of bFGF and IGF-1 were obversly higher.Compared with control group,western blot showed that the expression levels of MMP2 and MMP9 were much higher,especially the levels of MMP2,the difference was statistically significant(P<0.05).Conclusion:Intimal hyperplasia is the main cause of dysfunction of AVF.SMCs may migrate and express bFGF、IGF-1 and MMP2 to sustain the venous continued neointimal hyperplasia.