Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice
Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice
复制标题
DOI：
10.1016/0047-6374(96)01737-x
复制
发表时间：
1996-07-31
影响因子：
5.3
通讯作者：
Wolf, NS
中科院分区：
文献类型：
--
作者：
Reed, MJ;Penn, PE;Wolf, NS
与随意喂养（AL）的老年小鼠相比，接受长期热量限制（CR）的老年小鼠改善了健康状况，延长了寿命。然而，热量限制对老年小鼠的伤口愈合受损没有好处。为了验证CR小鼠具有增强伤口修复能力的假设，但需要短期额外的营养摄入来显示这一优势，我们评估了在受伤前4周无限制饮食的CR小鼠的伤口愈合情况。研究了两种AL青年（yal）（4-6个月）、AL中年（M AL）（15-17个月）和三种不同的、匹配的老年小鼠(O)（30-33个月）：O AL、O CR和O RF。在每只小鼠的背部制造2个直径为4mm的全厚度穿刺活检皮肤创面。分别于伤后1、2、3、5和7天处死动物并收获伤口。与Y AL和M AL动物相比，O AL和O CR小鼠的伤口修复速度较慢。相比之下，通过伤口面积和组织学标准来评估，O RF小鼠的愈合情况与Y AL和M AL小鼠相似。与O AL和O CR小鼠相比，O RF小鼠的I型胶原mRNA合成增强。通过BrdU的摄取测量，O RF小鼠伤口边缘的内皮细胞和成纤维细胞的数量更多，在体内表现出复制。O RF小鼠具有较高水平的胰岛素样结合蛋白3 （IGFBP-3）。此外，与来自O AL小鼠的成纤维细胞相比，来自O CR小鼠皮肤穿孔活检外植体的成纤维细胞在体外显示出增强的增殖和收缩。总之，与O AL小鼠相比，O RF小鼠表现出更强的伤口修复能力。这种效果似乎部分是通过增强细胞增殖、收缩和胶原蛋白生物合成介导的。此外，短期再喂养诱导血清IGFBP-3 （IGF-1的主要结合蛋白）水平升高。这些数据证实，来自CR动物的细胞具有保留的增殖、生物合成和收缩能力，但需要足够的营养来源才能在伤口愈合中证明这种优势。
Aged mice that have undergone long-term caloric-restriction (CR) have improved health and enhanced longevity in comparison to aged mice that are ad libitum-fed (AL). However, caloric-restriction does not benefit the impaired wound healing of aged mice. To test the hypothesis that CR mice have the capacity for enhanced wound repair, but require a short-term period of additional nutrient intake to show this advantage, we assessed wound healing in CR mice that had been refed (RF) an ad libitum diet for 4 weeks prior to wounding. Two strains of AL young (Y AL) (4-6 months), AL middle-aged (M AL) (15-17 months), and three different, matched cohorts of old mice (O) (30-33 months): O AL, O CR, and O RF were studied. Two full-thickness 4 mm diameter punch biopsy skin wounds were created on the dorsum of each mouse. Animals were sacrificed and wounds were harvested at 1, 2, 3, 5, and 7 days post-wounding. Repair of wounds was slower in O AL and O CR mice compared to Y AL and M AL animals. In contrast, the O RF mice healed similarly to that of the Y AL and M AL mice, as assessed by measures of wound area and histologic criteria. O RF mice demonstrated enhanced synthesis of type I collagen mRNA in comparison to O AL and O CR mice. A greater number of endothelial cells and fibroblasts at the wound edge of the O RF mice exhibited replication in vivo as measured by uptake of BrdU. O RF mice had higher levels of insulin-like binding protein 3 (IGFBP-3). Furthermore, fibroblasts derived from the explant of the punch biopsy of O CR mouse skin revealed enhanced proliferation and contraction in vitro, in comparison to fibroblasts from the O AL mice. In conclusion, O RF mice demonstrate an enhanced capacity to undergo wound repair in comparison to O AL mice. This effect appears to be mediated, in part, by enhanced cell proliferation, contraction, and collagen biosynthesis. In addition, short-term refeeding induced an increase in the serum level of IGFBP-3, the major binding protein for IGF-1. These data confirm that cells from a CR animals have a preserved proliferative, biosynthetic, and contractile capacity, but that an adequate source of nutrients is necessary to demonstrate this advantage in wound healing.