Analysis of angiogenesis in fibrinolytic factordefficient mice

纤溶因子缺陷小鼠血管生成分析

• 批准号: 09670062
• 负责人: MATSUO Osamu
• 金额: $ 1.86万
• 依托单位: Department of Physiology, Kinki University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670062/
• 关键词: Fibrinolysis; t-PA; u-PA; PAl-1; PLGF; Capsule; Knock out mouse; Fibrin; Angiogenesis; Endothelial cells

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.

分别建立缺失胎盘生长因子（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剂（PAl-1）基因的小鼠系。胶囊植入法可用于分析这些小鼠的伤口愈合过程，因为在胶囊植入后观察到肉芽组织和组织液的形成呈时间依赖性增加。该模型表明，与野生型小鼠相比，缺乏PLGF延迟了伤口愈合早期胶囊内肉芽组织的形成。然而，在胶囊中存在纤维蛋白时，它得到了显着改善，这表明纤维蛋白是诱导组织修复的良好基质。该方法同样适用于不同纤溶因子小鼠。纤维蛋白胶囊对不同纤溶因子小鼠肉芽组织再生也有一定的促进作用。然而，这些小鼠的组织修复率没有差异。囊内液体和囊内组织提取物中基质金属蛋白酶的活性以及培养的内皮细胞的增殖均不受这些纤溶因子缺乏的影响。因此，在胶囊植入模型中，u-PA、t-PA和PAl-1对血管生成过程的影响不明显。