Kobayashi Nobuhiko, DeLano Frank A, Schmid-Schönbein Geert W
Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2114-21. doi: 10.1161/01.ATV.0000178993.13222.f2. Epub 2005 Jul 21.
Endothelial cell apoptosis caused by oxidative stress may lead to the loss of microvessels (rarefaction) in hypertension. We examine here the effects of antioxidants on cell apoptosis and rarefaction.
The juvenile spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with superoxide scavengers, Tempol or Tiron, during growth. After the treatment, oxidative stress status, endothelial cell apoptosis rate, and microvessel length density in skeletal muscle and mesentery were evaluated in comparison with age-matched controls. Untreated 16-week-old SHR had higher oxidative stress (P<0.01) and cell apoptosis rate (P<0.05) and lower microvessel length density (371+/-17 mm/mm3 [P<0.01]) compared with age-matched WKY rats (435+/-15 mm/mm3). In the SHR, but not in WKY rats, systemically applied antioxidants attenuated oxidative stress and cell apoptosis rate (P<0.05 versus untreated controls) and prevented the loss of microvessels (411+/-15 mm/mm3 for Tempol [P<0.01 versus untreated control] and 399+/-17 mm/mm3 for Tiron [P<0.05]).
Antioxidant treatment with cell-permeable superoxide scavengers inhibits endothelial cell apoptosis and prevents microvessel rarefaction in the SHR during growth.
氧化应激引起的内皮细胞凋亡可能导致高血压患者微血管的丢失（稀疏化）。我们在此研究抗氧化剂对细胞凋亡和稀疏化的影响。
幼年自发性高血压大鼠（SHR）和血压正常的Wistar-Kyoto（WKY）大鼠在生长过程中用超氧化物清除剂Tempol或Tiron进行治疗。治疗后，与年龄匹配的对照组相比，评估骨骼肌和肠系膜中的氧化应激状态、内皮细胞凋亡率和微血管长度密度。与年龄匹配的WKY大鼠（435±15mm/mm³）相比，未经治疗的16周龄SHR具有更高的氧化应激（P<0.01）和细胞凋亡率（P<0.05）以及更低的微血管长度密度（371±17mm/mm³ [P<0.01]）。在SHR中，而非WKY大鼠中，全身应用抗氧化剂可减轻氧化应激和细胞凋亡率（与未治疗的对照组相比，P<0.05）并防止微血管丢失（Tempol为411±15mm/mm³ [与未治疗的对照组相比，P<0.01]，Tiron为399±17mm/mm³ [P<0.05]）。
用可透过细胞的超氧化物清除剂进行抗氧化治疗可抑制SHR生长过程中的内皮细胞凋亡并防止微血管稀疏化。
