Natural Killer Cell Reduction and Uteroplacental Vasculopathy
Natural Killer Cell Reduction and Uteroplacental Vasculopathy
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DOI：
10.1161/hypertensionaha.116.07800
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发表时间：
2016-10-01
期刊：
影响因子：
8.3
通讯作者：
Dechend, Ralf
中科院分区：
文献类型：
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作者：
Golic, Michaela;Haase, Nadine;Dechend, Ralf
子宫自然杀伤细胞对子宫胎盘发育和妊娠维持非常重要。它们在妊娠障碍如先兆子痫中的作用尚不清楚。我们通过在建立的大鼠先兆子痫模型（雌性人血管紧张素原xmale人肾素）中给予兔抗去唾液酸GM 1抗血清来减少自然杀伤细胞的数量，并在妊娠结束时（第21天）与接受正常兔血清的先兆子痫对照大鼠进行比较。在100%的抗血清治疗的先兆子痫大鼠（7/7）中，我们观察到妊娠结束时子宫系膜三角区的血管横截面高度变性。这种母体子宫血管病变的特征是血管壁中完全缺乏有核/活细胞，血管周围明显存在纤维化。此外，血管腔内没有血管内滋养层细胞。在对照组，正常兔血清处理的先兆子痫大鼠中，只有20%（1/5）的动物显示出这种血管病变。我们证实了健康妊娠野生型大鼠的结果：抗去唾液酸GM 1治疗后，67%的母体大鼠在妊娠结束时显示血管病变，而兔血清治疗的对照大鼠为0%。这种血管病变与野生型大鼠胎仔体重显著降低和先兆子痫大鼠胎仔脑/肝重量比恶化相关。抗去唾液酸GM 1应用对妊娠期母体高血压和蛋白尿无影响。我们的研究结果显示了自然杀伤细胞在妊娠高血压期间维持血管完整性的新作用。在血压正常的妊娠中，这种完整性似乎对胎儿的生长很重要。
Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogenxmale human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.