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Biomechanics on Remodeling of Biological Tissues - Role of Collagen Cross-Linking

生物组织重塑的生物力学——胶原蛋白交联的作用

基本信息

批准号：
18500354
负责人：
HAYASHI Kozaburo
金额：
$ 2.56万
依托单位：
Okayama University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

The area fractions of collagen and elastin in the rat common carotid artery did not change between 8 and 64 weeks, whereas the elastic modulus of wall was significantly larger in 64 weeks old animals compared to younger ones. To know the reason, we have applied a hydromechanical isometric tension method to the analysis of cross-linking of collagen. In the method, a tissue specimen is stretched and heated to above collagen denaturation temperature, and kept at this temperature under constant strain condition. Stress relaxation observed thereafter indicates a measure of the amount of thermally stable, matured cross-linking ; stress reduction is a measure of cross-linking.First, we studies age-related changes of cross-linking in arterial wall using rat common carotid arteries aged 8, 16, 32, and 64 weeks. Small rectangular specimens were attached to a specially designed test apparatus, and immersed in distilled water in a thermostatic bath. While a tensile strain (in vivo strain) was applied to each specimen, specimen temperature was elevated to 100C. While the specimen was kept under this condition, force developed in the specimen was continuously monitored. Half-value period of load, i.e. the time elapsed for the reduction of load to a half, was used as a measure of cross-linking, and it was significantly longer in 64 weeks old animals than in younger ones. This result corresponds well to the results of the elastic modulus of wall, indicating that higher wall stiffness in older arteries is attributable to the larger amount of stable collagen cross-linking. Then, the HIT method was applied to common carotid arteries from DOCA-salt hypertensive rats, and the results were compared with those from the age-matched, normotensive animals. Relative amount of matured cross-links showed a tendency of increasing by hypertension, which explains higher elastic modulus in hypertensive arteries than in normotensive ones.

大鼠颈总动脉中胶原蛋白和弹性蛋白的面积分数在8 ~ 64周龄之间没有变化，而颈总动脉壁弹性模量在64周龄大鼠明显大于幼鼠。为了了解其原因，我们应用了流体力学等张力法来分析胶原蛋白的交联。在该方法中，将组织试样拉伸并加热到胶原变性温度以上，并在恒应变条件下保持在该温度。之后观察到的应力松弛表明了热稳定的成熟交联量的测量；减压是一种交联的方法。首先，我们使用8、16、32和64周龄大鼠颈总动脉研究动脉壁交联的年龄相关变化。小的矩形试样连接在一个专门设计的测试装置上，并浸泡在恒温浴的蒸馏水中。当对每个试样施加拉伸应变（体内应变）时，将试样温度升高到100℃。在此条件下，连续监测试样的受力情况。负荷的半值期，即负荷减少到一半的时间，被用作交联的衡量标准，64周龄的动物比年轻的动物明显更长。这一结果与管壁弹性模量的结果很好地对应，表明老年动脉的管壁刚度较高是由于稳定的胶原交联量较大。然后，将HIT方法应用于doca盐高血压大鼠颈总动脉，并将结果与年龄匹配、血压正常的动物进行比较。成熟交联的相对数量随高血压的增加而增加，这说明高血压动脉的弹性模量高于正常动脉。