【作者】 孟令强；

【导师】 高美华；

【作者基本信息】 青岛大学 ， 病原生物学， 2004， 硕士

【摘要】 目的 从分子水平研究刺激性免疫分子和与细胞凋亡有关因子在糖尿病血管病变中的变化，探讨这些免疫分子之间以及这些免疫分子与糖尿病血管病变发生发展之间的相关性，为早期防治糖尿病血管并发症提供一定的理论依据。 方法 应用酶联免疫吸附实验法(ELISA)测定30例正常人和64例2型糖尿病患者血浆血小板衍化生长因子(PDGF-BB)、血管内皮生长因子(VEGF)、可溶性Fas(sFas)和可溶型补体末端复合物(sC5b-9)的含量。 结果 ①2型糖尿病组与正常对照组比较，血浆sC5b-9含量明显升高(P＜0.01)。②2型糖尿病组与正常对照组比较，血浆PDGF-BB含量明显升高(P＜0.01)。2型糖尿病有血管病变组与糖尿病无血管病变组相比，血浆PDGF-BB明显增高(P＜0.05)。③2型糖尿病组与正常对照组比较，血浆VEGF含量明显升高(P＜0.01)。2型糖尿病有血管病变组与糖尿病无血管病变组相比，血浆VEGF明显升高，差异显著(P＜0.05)。④2型糖尿病组与正常对照组比较，血浆sFas含量明显升高(P＜0.01)。2型糖尿病有血管病变组与糖尿病无血管病变组相比，血浆sFas明显升高(P＜0.05)。 结论 PDGF-BB、VEGF、sFas和补体末端复合物sC5b-9参与了糖尿病血管病变的发生和发展，其可能机制是：长期高血糖使补体调节蛋白CD59被糖化，其抑制补体末端复合物C5b-9形成的功能受损，sC5b-9生成增多。sC5b-9与血管内皮细胞和平滑肌细胞结合致使内皮细胞和平滑肌细胞损伤活化，内皮细胞和平滑肌细胞释放刺激性免疫分子，主要为PDGF-BB和VEGF，另外，PDGF-BB对VEGF的表达具有正调节作用。PDGF-BB和VEGF通过和内皮细胞、平滑肌细胞上相应受体结合，促使平滑肌细胞、单核巨噬细胞、内皮细胞增生和内膜下迁移，同时产生和分泌多种生长因子，再通过自分泌和旁分泌作用，进一步促进这些细胞增殖；内皮细胞和平滑肌细胞损伤活化高表达sFas，sFas通过与细胞膜Fas竞争与Fas配体结合拮抗Fas产生凋亡，使凋亡信号中文摘要减弱。刺激信号的增强、凋亡信号的减弱最终导致糖尿病血管病变的发生和发展。更多还原

【Abstract】 Objective To study the change of irritative immune molecules and factor about cell apoptosis and the relationship between these immune molecules and development of diabetic angiopathy and to provide academic basis for the prevention of diabetic vascular complications.Methods Plasma sC5b-9, PDGF-BB, VEGF and sFas levels were determined by an enzyme-linked immunosorbent assay in 64 cases of non-insulin-dependent diabetes mellitus (NIDDM) and 30 cases of healthy individuals.Results The levels of sC5b-9, PDGF-BB,VEGF and sFas in patients with NIDDM were significantly higher than those in healthy individuals(P<0.01). Levels of PDGF-BB, VEGF and sFas in DM patients with vascular disease were significantly higher than those in DM patients without vascular disease (P<0.05).Conclusions sC5b-9, PDGF-BB, VEGF and sFas may be involved in development and progress of diabetic angiopathy. Long increased glucose level in diabetes causes complement regulatory membrane protein CD59 glycation, which impairs its function to restrict C5b-9 formation. sC5b-9 increases. Insertion of the C5b-9 into endothelial cell and smooth muscle cell membranes causes these cells activation and the release of irritative immune molecules from endothelial cells and smooth muscle cells. These immune molecules mainly contain PDGF-BB and VEGF. In addition, PDGF-BB has certain up-regulation on expression of VEGF. By binding to relevant receptors on endothelial cells and smooth muscle cells, PDGF-BB and VEGF promote proliferation of smooth muscle cells, monocyte-macrophages and endothelial cells and the release of several growth factors which then further promote these cells proliferation by the way of autocrine and paracrine pathway. Activated endothelial cells and smooth muscle cells express sFas which competitively bind Fas ligand with Fas to reverse apoptosis that Fas reduced. Both increased stimulationsignal and decreased apoptosis signal lead to development and progress of diabetic angiopathy.更多还原