Department of General and Transplant Surgery, University of Tübingen, Tübingen, Germany.
Surgery. 2010 Jun;147(6):780-8. doi: 10.1016/j.surg.2009.11.003. Epub 2010 Jan 4.
There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.
One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and 1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.), xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days. Wound-healing was monitored by planimetry and oxygen tension in periphery of the wound using a microcatheter probe. Cellular proliferation in granulation tissue was assessed by immunohistochemical detection of proliferating cell nuclear antigen. The angiogenic activity of isoniazid and niacin was assessed using in vitro and ex vivo models.
Although wound ischemia was evident by decreased oxygen tension (26 +/- 10 mmHg; n = 9) compared with the adjacent nonischemic wounds (51 +/- 8 mmHg; n = 8), neither compound significantly influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin, promoted ischemic wound-healing even though both compounds increased proliferation measured on day 14 (P < .01). In normal wounds, the cumulative change in relative wound area over 14 days was increased by niacin (P = .002), but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036) increased cellular proliferation. Neither isoniazid nor niacin showed activity in either an endothelial tube formation assay or organotypic angiogenic assay under normoxic conditions.
Isoniazid was capable of stimulating wound-healing in ischemic tissue to the level of nonischemic wounds and might offer a novel treatment option for wounds associated with arterial insufficiency. Although active in normal wounds, niacin did not promote ischemic wound-healing.
需要有效的治疗缺血性伤口。我们的目的是检验这样一个假设，即异烟肼或烟酸的全身给药可以增强缺血和非缺血组织中的伤口愈合。
在雄性 Sprague-Dawley 大鼠背部的标准化缺血皮瓣和相邻的非缺血皮上各制造一个 8 毫米全厚的伤口。在受伤后立即开始，每天两次腹膜内给予异烟肼（10mg/kg b.i.d.）、烟酸肌醇酯（30mg/kg）或生理盐水（对照），共 14 天。通过面积测定法和使用微导管探头监测伤口周围的氧分压来监测伤口愈合。通过增殖细胞核抗原的免疫组织化学检测评估肉芽组织中的细胞增殖。使用体外和离体模型评估异烟肼和烟酸的血管生成活性。
尽管伤口缺血导致氧分压降低（26±10mmHg；n=9），与相邻的非缺血伤口（51±8mmHg；n=8）相比，但两种化合物均未显著影响皮内氧分压。异烟肼（P<0.0001），而不是烟酸，促进了缺血性伤口愈合，尽管两种化合物在第 14 天均增加了增殖（P<0.01）。在正常伤口中，14 天内相对伤口面积的累积变化因烟酸而增加（P=0.002），但异烟肼则没有，尽管烟酸（P=0.011）和异烟肼（P=0.036）均增加了细胞增殖。在正常氧条件下，异烟肼和烟酸均未在血管生成管形成测定或器官型血管生成测定中显示活性。
异烟肼能够刺激缺血组织的伤口愈合达到非缺血组织的水平，可能为动脉功能不全相关的伤口提供一种新的治疗选择。尽管在正常伤口中有效，但烟酸并未促进缺血性伤口愈合。
