The role of neutrophil induced oxidative damage in the pathpgenesis of preeclampsia

中性粒细胞诱导的氧化损伤在先兆子痫发病机制中的作用

• 批准号: 18591804
• 负责人: TSUKIMORI Kiyomi
• 金额: $ 2.4万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591804/
• 关键词: Preeclampsia; Neutrophil; Superoxide; Oxidative Damage

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.

为了阐明子痫前期的发病机制，我们从中性粒细胞诱导的氧化损伤的角度探讨了胎盘不良与母体内皮细胞功能障碍的关系。首先，我们研究了子痫前期中中性粒细胞与内皮细胞的相互作用。在先兆子痫中，中性粒细胞产生的 O_2 相对于 NO 的产生占主导地位，导致产生 O_2 衍生物、过氧化氢 (H_2O_2) 和 ONOO-，这两种物质都会直接损伤内皮细胞。此外，先兆子痫的特征是存在增强中性粒细胞超氧化物产生的血清因子。产后血清对子痫前期中性粒细胞 O_2 生成的增强作用消失，表明胎盘缺血可能在启动子痫前期所见的全身中性粒细胞活化中起重要作用。接下来，我们研究了一氧化氮合成酶 (NOS) 抑制剂 N-硝基精氨酸甲酯 (L-NAME) 对子痫前期形态变化的影响。 胎盘形成初期妊娠大鼠的胎盘、母体血压和血清TNF-a。妊娠中期的 NOS 抑制与动脉压、胎盘细胞凋亡和血清 TNF-a 的增加有关，所有这些都与先兆子痫的病理生理学特征有关。这些发现表明，胎盘缺血/缺氧导致母体中性粒细胞活性氧自由基 (ROS) 的产生，这是母体炎症细胞因子产生增强的结果， 中性粒细胞产生的ROS增加可能介导先兆子痫女性的内皮损伤。

项目成果

Difference in neutrophil superoxide generation during pregnancy between preeclampsia and essential hypertension

先兆子痫和原发性高血压妊娠期间中性粒细胞超氧化物生成的差异

• 发表时间: 2007
• 期刊: Hypertension 49
• 作者: Tsukimori K;et. al.
• 通讯作者: et. al.

Increased inflammatory markers are associated with early periventricular leukomalacia

• DOI: 10.1111/j.1469-8749.2007.00587.x
• 发表时间: 2007-08
• 期刊: Developmental Medicine & Child Neurology
• 影响因子: 3.8
• 作者: K. Tsukimori;H. Komatsu;Takazumi Yoshimura;S. Hikino;T. Hara;N. Wake;H. Nakano

Preeclampsia and Preterm delivery

先兆子痫和早产

• 发表时间: 2006
• 期刊: Advanced Medicine, Obstetrics Gynecology Sentan-iryo Co., Ltd.
• 作者: Tsukimori;K
• 通讯作者: K

Neutrophil-derived reactive oxygen species can modulate neutrophil adhesion to endothelial cells in preeclampsia.

中性粒细胞衍生的活性氧可以调节先兆子痫中中性粒细胞与内皮细胞的粘附。

• DOI: 10.1038/ajh.2007.87
• 发表时间: 2008
• 期刊: American journal of hypertension
• 影响因子: 3.2
• 作者: K. Tsukimori;Akitoshi Tsushima;K. Fukushima;H. Nakano;N. Wake
• 通讯作者: N. Wake

Neutrophil function during pregnancy:Is nitric oxide production correlated with superoxide production?

怀孕期间的中性粒细胞功能：一氧化氮的产生与超氧化物的产生相关吗？

• 发表时间: 2006
• 期刊: Am J Reprod Immunol 55
• 作者: Tsukimori K;et. al.
• 通讯作者: et. al.