Hyperoxia and angiogenesis
Hyperoxia and angiogenesis
复制标题
DOI：
10.1111/j.1524-475x.2005.00078.x
复制
发表时间：
2005-11-01
影响因子：
2.9
通讯作者：
Hunt, TK
中科院分区：
文献类型：
--
作者：
Hopf, HW;Gibson, JJ;Hunt, TK
我们假设组织高氧会增强伤口模型中的新血管形成，而组织缺氧会抑制新血管形成。因此，我们使用雌性 Swiss-Webster 小鼠来研究差氧治疗对血管生成的影响。将一毫升Matrigel(R) 塞子皮下注射到小鼠体内，Matrigel(R) 是一种基质蛋白的混合物，支持血管生成但本身并不引发血管生成。使用Matrigel 时不添加添加剂或添加血管内皮生长因子(VEGF)或抗VEGF抗体。将动物维持在低氧、常氧或四种高氧环境之一：低氧-13％氧气，1个绝对大气压（ATA）；含氧量正常 - 1 ATA 时含氧量为 21%；高氧-（a-d 组）100% 氧气，每天两次，每次 90 分钟，压力如下：a 组，1 ATA； b 组，2 ATA； c 组，2.5 ATA； d 组，3.0 ATA。测量所有组的皮下氧分压。植入后7天除去Matrigel 。通过显微镜对切片进行分级以确定新血管形成的程度。与暴露于室内空气的对照组相比，所有高氧组的血管生成均显着增加，而缺氧组的血管生成则显着减少。抗 VEGF 抗体消除了 VEGF 的血管生成作用并增加了氧张力。我们得出结论，血管生成在很大范围内与环境 pO(2) 成正比。这证实了血管生成需要氧气的临床印象。间歇性吸氧可以满足缺血组织对氧气的需要。
We hypothesized that tissue hyperoxia would enhance and hypoxia inhibit neovascularization in a wound model. Therefore, we used female Swiss-Webster mice to examine the influence of differential oxygen treatment on angiogenesis. One milliliter plugs of Matrigel(R), a mixture of matrix proteins that supports but does not itself elicit angiogenesis, were injected subcutaneously into the mice. Matrigel(R) was used without additive or with added vascular endothelial growth factor (VEGF) or anti-VEGF antibody. Animals were maintained in hypoxic, normoxic, or one of four hyperoxic environments: hypoxia-13 percent oxygen at 1 atmosphere absolute (ATA); normoxia-21 percent oxygen at 1 ATA; hyperoxia-(groups a-d) 100 percent oxygen for 90 minutes twice daily at the following pressures: Group a, 1 ATA; Group b, 2 ATA; Group c, 2.5 ATA; Group d, 3.0 ATA. Subcutaneous oxygen tension was measured in all groups. The Matrigel(R) was removed 7 days after implantation. Sections were graded microscopically for the extent of neovascularization. Angiogenesis was significantly greater in all hyperoxic groups and significantly less in the hypoxic group compared with room air-exposed controls. Anti-VEGF antibody abrogated the angiogenic effect of both VEGF and increased oxygen tension. We conclude that angiogenesis is proportional to ambient pO(2) over a wide range. This confirms the clinical impression that angiogenesis requires oxygen. Intermittent oxygen exposure can satisfy the need for oxygen in ischemic tissue.