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关键词: 血管生成,血管生长因子,抗血管生成因子,基因治疗
血管生成(Angiogenesis)[1]是从先存血管产生新血管的过程,血管生成可发生在伤口愈合、子宫内膜周期性变化、肿瘤、心肌梗塞后和糖尿病。而血管再建(Revascula rization)[2]则包括人工和生物两方面,其中有血管修复、再通和侧支循环的形成,可见于冠状动脉的溶栓、PTCA术和支架均属于血管再建的范畴。血管新生(Neovasculariz ation or neoangiogenesis)[3,4]在血管生成的初始,首先是血管内皮细胞去分化,在各种条件具备的情况下,血管基底膜变薄或和消失,内皮细胞游走并增殖,新基底膜形成,覆盖以内皮细胞和血管平滑肌细胞,最后形成新的血管。那么,目前对这一切的发生机制是怎么样认识的?
1 血管生成的机制
在肿瘤组织中新生血管的研究发现[5]:在血管内皮细胞基底膜降解,具有血管攀的新内皮细胞生长之前,有一系列的生化过程发生,如各种蛋白酶合成增加,血管渗漏纤维蛋白原和血浆酶原,组织因子被激活,局部高凝固性和血管外纤维素沉积,细胞粘附分子增加等。后来又离出许多血管生长因子,见表1,包括酸性和碱性纤维母细胞生长因子(Fi broblast growth factor,FGF)[6],以及血管内皮生长因子家族(Vascular endoth elial growth factor,VEGF)[7]。目前这两个因子在血管生成研究中最受关注。VE gF是由低氧和低血糖诱导,并且与两个酪氨酸激酶家族的特异性受体(KDR)和(FIT-1)结合,两个受体对内皮细胞具有正向调节作用。同时人们又发现体内存在大量抑制正常血管生成的抗血管生成因子,需要“关闭”这些抗血管生成因子才能使血管生成发生,见表2。其中血管抑制素(Angiostatin)[8]和内抑制素(Endostatin)[9]作用最重要。但目前尚不肯定它们的作用。Standker只是把内抑制素从肿瘤组织中提纯,证实是一种血浆纤溶酶原。
促血管生成因子和抗血管生成因子两大系统之间是怎样的关系?又是怎样获得平衡?目前均不清楚。现在仅仅是对这些因子进行深入的研究。现就了解的情况作一总结如表1和表2。
目录:
1 血管生成的机制
2 临床应用血管生成治疗存在的问题及展望
参考文献:
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