| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
To clarify the pathogenesis of preeclampsia, we investigated the relationship between poor placentation and the maternal endothelial cell dysfunction from the viewpoint of neutrophil induced oxidative damage.
Firstly, we studied neutrophil endothelial interaction in preeclampsia. In preeclampsia, the dominance of neutrophil O_2 production over NO production results in the elaboration of the O_2 derivatives, hydrogen peroxide (H_2O_2), and ONOO-, both of which directly damage endothelial cells. In addition, preeclampsia is characterized by the presence of serum factors that enhance neutrophil superoxide production. The postpartum disappearance of the serum enhancing effect on neutrophil O_2 production in preeclampsia suggesting that placental ischemia may be important in initiating the systemic neutrophil activation seen in preeclampsia.
Next, we studied the effect of N-nitro-arginine methyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, on morphologic changes in the placenta, maternal blood pressure and serum TNF-a in pregnant rats during the initial stage of placentation. The NOS inhibition at mid-gestation in pregnant rats is associated with increases in arterial pressure, placental apoptosis and serum TNF-a, all of which have been implicated as pathophysiological features of preeclampsia.
These findings suggest that placental ischemia/hypoxia causes maternal neutrophil reactive oxygen radicals (ROS) production as a consequence of enhanced maternal production of inflammatory cytokines, and that the increased ROS produced by neutrophils may mediate the endothelial damage in women with preeclampsia.
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