Analysis of angiogenesis in fibrinolytic factordefficient mice

建立胎盘生长因子(PLGF)、尿激酶型纤溶酶原激活物(u-PA)、组织型纤溶酶原激活物(t-PA)和1型纤溶酶原激活物抑制物(PAL-1)基因缺失的小鼠系。包囊植入法可用于分析这些小鼠的伤口愈合过程，因为包囊植入后肉芽组织和组织液的形成呈时间依赖性地增加。这一模型表明，与野生型小鼠相比，在伤口愈合的早期阶段，PLGF的缺乏延迟了包膜内肉芽组织的形成。然而，在胶囊中存在纤维蛋白时，它得到了相当大的改善，这表明纤维蛋白是诱导组织修复的良好基质。该方法同样适用于纤溶因子不同的小鼠。胶囊中的纤维蛋白对纤溶因子不同的小鼠肉芽组织的再生也是有效的。然而，这些小鼠之间的组织修复速度没有差异。这些纤溶因子的缺乏既不影响囊内液和囊内组织提取液中基质金属蛋白酶的活性，也不影响培养内皮细胞的增殖。因此，在包膜植入模型中，u-PA、t-PA和PAL-1对血管生成过程的影响不明显。

The mouse lines which lack the genes for placenta growth factor(PLGF), urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAl-1 ), respectively were established. The capsule-implantation method was useful for the analysis of wound healing process in these mice, since the formation of granulation tissues and tissue fluids were observed to be increased in a time dependent manner after the implantation of capsules. This model demonstrated that the lack of PLGF delayed the formation of granulation tissues inside the capsule at an early stage of wound healing compared with that of wild-type mouse. However, it was considerably improved in the presence of fibrin in the capsule, suggesting that fibrin acted as a good matrix for inducing tissue repair. This method was also applicable in the fibrinolytic factor-diffecient mice. The effect of fibrin in the capsule was also found to be effective for the regeneration of granulation tissues in ery fibrinolytic factor-diffecient mouse. However, there was no difference in the rate of tissue repair among these mice. Neither activities of matrix metalloproteinases in the intracapsular fluids and intracapsular tissue extracts, nor the proliferation of cultured endothelial cells were not influenced by the defficiency of these fibrinolytic factors. Therefore, the effect of u-PA, t-PA and PAl-1 on the process of angiogenesis was not evident by the capsule-implantation model.