动脉中膜平滑肌细胞凋亡促进受体骨髓细胞参与移植物动脉硬化的研究-外科学(普外科)专业论文.docxVIP

免疫组化显示靶基因 p53 和 Bcl-XL 在移植动脉壁特异性表达，且以移植动 脉中膜为主。病理组织学分析提示 p53 基因转染特异性诱导移植动脉中膜平滑肌 细胞凋亡，引起血管壁 SDF-1α 和 TGF-β 表达明显升高，并促进移植动脉新生内 膜形成及动脉硬化；而 Bcl-XL 基因转染显著抑制中膜平滑肌细胞凋亡，下调 SDF-1α 和 TGF-β 表达水平，从而减少移植动脉内膜增生。PCR 分析提示 p53 转 染组新生内膜细胞中的雄性来源细胞 (Sry mRNA 水平) 较载体组显著增多 (P0.01) ，而 Bcl-XL 组新生内膜细胞中的雄性来源细胞较载体组显著减 少 (P0.01)。 研究结论： 移植动脉中膜平滑肌细胞凋亡通过上调 SDF-1α 和 TGF-β 表达诱导受体外周 血骨髓干细胞迁移至移植动脉内膜，并诱导其分化增殖为新生内膜细胞，促进移 植物动脉内膜增生及动脉硬化 【关键词】移植；动脉硬化；细胞凋亡；血管平滑肌细胞；骨髓细胞 Abstract Background：Transplant arteriosclerosis (TA) caused by chronic rejection is the major factor of chronic transplant dysfunction. Transplant arteriosclerosis is characterized by neointimal proliferation. Diffusive intimal hyperplasia modifies blood flow, ultimately leading to allograft ischemic and loss of function. Recipient bone marrow cells migrating and differentiating into vascular smooth muscle cells (VSMCs) contribute to allograft artery neointimal expansion. However, the role of medial smooth muscle cells in this process still remains to be established. Objective: To explore the biological function and its molecular mechanism of VSMCs apoptosis in the development of allograft neointimal proliferation via recipient bone marrow cells. Method and results: Aortic transplant was performed on sex-mismatched bone marrow transplantation from male SD rats to female SD rats. Lentivirus vectors carried with p53 or Bcl-XL which were promoted by specific SMC-promoter SM22α were employed to transfect into aortic allograft. Then the aortic grafts were harvested for histological evaluation and immunohistochemistry. The results indicated that allograft artery transfected with p53 promotes medial VSMCs apoptosis and increases the expression of SDF-1α and TGF-β, subsequently induces allograft neointimal proliferation. Conversely, apoptosis of medial VSMCs inhibited by transfection of Bcl-XL reduces the expression of SDF-1α and TGF-β and decreases the neointimal formation in allograft artery. PCR assay demonstrates that apoptosis of medial