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1 Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582; and 2 Department of Clinical Research, National Ohkura Hospital, Tokyo 157-0063, Japan
We
investigated leukocyte involvement in uterine hypoperfusion and
intrauterine fetal growth retardation (IUGR) induced by ischemia-reperfusion (I/R) in Sprague-Dawley rats. On day
17 of gestation, leukocyte accumulation in the uterus and placenta
subjected to 30 min of ischemia, followed by reperfusion, was
assessed by measuring myeloperoxidase (MPO) activity. Uterine MPO
activity was significantly higher after 1 h of reperfusion than it
was before ischemia (P < 0.05), without any
increase in placental MPO activity. Immunohistochemical staining showed
leukocyte accumulation in the uterus subjected to I/R. The effects of
treatment with monoclonal antibodies against CD11a (WT1) and CD18 (WT3)
at a dose of 0.8 mg/kg on uterine blood flow and IUGR were
investigated. Laser-Doppler flowmetry demonstrated that uterine
hypoperfusion at 2 h after ischemia (blood flow,
51.7 ± 1.2%; P < 0.01) was inhibited by WT1 and
WT3 treatment. I/R-induced IUGR at full term (P < 0.05 vs. nonischemic horn) was prevented by WT1 and WT3 treatment on
day 17. These results indicate that leukocyte accumulation may play an important role in the pathogenesis of uterine hypoperfusion and IUGR induced by I/R in pregnant rats.
uterine blood flow; CD11/CD18 integrin; rat
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