Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations
Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations
复制标题
DOI：
10.1046/j.1524-475x.2001.00223.x
复制
发表时间：
2001-05-01
影响因子：
2.9
通讯作者：
Davidson, JM
中科院分区：
文献类型：
--
作者：
Ballas, CB;Davidson, JM
据报道，衰老会导致伤口愈合时间延长，对年轻大鼠（4个月大）和老年大鼠（36个月大）的穿刺活检伤口愈合的测量表明，老年大鼠在修复的早期阶段伤口愈合有显著延迟，之后的愈合率是相同的。老年动物肉芽组织积累的延迟可能涉及过早的程序性细胞死亡（细胞凋亡）；然而，老龄大鼠海绵肉芽组织和组织培养中凋亡成纤维细胞的数量相对于年轻大鼠较少。肌成纤维细胞表达a-平滑肌肌动蛋白，它们在伤口收缩中被认为是重要的。肉芽组织和培养肉芽组织成纤维细胞中含有a-平滑肌肌动蛋白的肌成纤维细胞的总体丰度和分布无显著差异，与供体年龄无关。肌成纤维细胞和凋亡细胞的空间分布明显。来自肉芽组织和皮肤外植体的成纤维细胞在第5代之前被置于胶原凝胶收缩实验中，以确定它们的体外收缩能力。尽管来自年轻和老年大鼠的肉芽组织成纤维细胞表现出相似的胶原凝胶收缩能力，但来自老年大鼠的皮肤成纤维细胞表现出比年轻皮肤成纤维细胞更大的胶原凝胶收缩行为。老年大鼠的成纤维细胞具有更强的凝胶收缩能力，这在很大程度上是由于这些细胞具有引起全面凝胶降解的能力。明胶酶谱显示，老年大鼠皮肤成纤维细胞凝胶的上清液中基质金属蛋白酶-2的丰度更高。综上所述，这些结果表明，大鼠年龄相关的愈合延迟可能与明显的肌成纤维细胞或凋亡细胞群的出现或丰度无关，蛋白水解可能在老年动物伤口愈合延迟中起重要作用。
Aging has been anecdotally reported to result in prolonged wound healing, Measurement of punch biopsy wound closure in young (4 month old) and old (36 month old) rats indicated there was a significant delay in wound closure by old rats during the early phase of repair, after which closure rates were equivalent. The delay in granulation tissue accumulation in older animals could involve premature programmed cell death (apoptosis); however, apoptotic fibroblasts in sponge granulation tissue and tissue culture were less abundant in samples from old rats relative to young rats. Myofibroblasts express a-smooth muscle actin, and they are believed to be important in wound contraction. There were no significant differences in overall abundance or distribution of a-smooth muscle actin containing myofibroblasts in granulation tissue and in cultured granulation tissue fibroblasts regardless of the age of the donor rat. The spatial distribution of myofibroblasts and apoptotic cells was distinct. Fibroblasts from granulation tissue and skin explants were placed in a collagen gel contraction assay prior to the 5(th) passage to determine their in vitro contractility, While granulation tissue fibroblasts from young and old rats showed similar collagen gel contractility, skin fibroblasts from old rats displayed greater collagen gel contractile behavior than young skin fibroblasts. Greater gel contractility of fibroblasts from old rats appeared to result, in large part, from the ability of those cells to cause generalized gel degradation. Gelatin zymography indicated a greater abundance of matrix metalloproteinase-2 in supernatants from gels containing skin fibroblasts from old rats, Taken together, these results suggest that the age-associated healing delay in the rat may not be related to the appearance or abundance of distinct myofibroblast or apoptotic cell populations, Proteolysis may have a significant role in delayed wound healing in aged animals.