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子痫前期转基因大鼠模型中的血管内滋养层细胞侵袭、螺旋动脉重塑及子宫胎盘血流动力学

Endovascular trophoblast invasion, spiral artery remodelling and uteroplacental haemodynamics in a transgenic rat model of pre-eclampsia.

作者信息

Geusens N, Verlohren S, Luyten C, Taube M, Hering L, Vercruysse L, Hanssens M, Dudenhausen J W, Dechend R, Pijnenborg R

机构信息

Department of Woman and Child, Katholieke Universiteit Leuven, Leuven, Belgium.

出版信息

Placenta. 2008 Jul;29(7):614-23. doi: 10.1016/j.placenta.2008.04.005. Epub 2008 May 27.

DOI:10.1016/j.placenta.2008.04.005
PMID:18502502
Abstract

The aim of the present study was to evaluate the depth of endovascular trophoblast invasion and associated remodelling of spiral arteries in a transgenic model of pre-eclampsia in the rat, a species showing a comparable deep invasion during normal pregnancy as the human. Pre-eclamptic (PE) transgenic rats (TGR) (hAngiotensinogen female x hRenin male) and non-PE reversely mated (RM) TGR rats were compared to normal Sprague-Dawley rats (C). Day 18 implantation sites were collected and the presence of endovascular trophoblast, fibrinoid, endothelial and smooth muscle cells were evaluated in spiral arteries in three parallel layers in the mesometrial triangle using an image analysis system (KS-400). In a separate group of animals peak-systolic and end-diastolic velocities were measured by Doppler in uterine and arcuate arteries, and the resistance indices (RI) were calculated. In PE and RM rats, the entire mesometrial triangle contained significantly more endovascular trophoblast and vascular fibrinoid deposits than the C group. No difference was found between the groups in the overall amount of smooth muscle surrounding the lumen, but in the PE and RM groups significantly more muscle was present in parts of the contours covered by trophoblast. There was significantly less CD31-positive endothelium in the total lumen contours of the PE and RM groups than in the C group, but in parts of the contours covered by trophoblast more residual endothelium was present in both TGR groups. Comparison of the three layers indicated deeper invasion in both the PE and RM groups than in the C group. By Doppler analysis of the proximal uterine artery the RI was found to be significantly lower in the PE and the RM group than in the C group. In the arcuate artery, the RI was significantly lower in the PE group as compared to the RM and C groups. We conclude that in this transgenic PE rat model there is deeper endovascular invasion of spiral arteries and decreased RI of uterine arteries at day 18 of pregnancy.

摘要

本研究的目的是在大鼠子痫前期转基因模型中评估血管内滋养层细胞浸润深度以及螺旋动脉的相关重塑情况,大鼠在正常妊娠期间与人类一样会出现类似深度的浸润。将子痫前期(PE)转基因大鼠(TGR)(h血管紧张素原雌性×h肾素雄性)和非PE反向交配(RM)的TGR大鼠与正常的斯普拉格-道利大鼠(C)进行比较。收集妊娠第18天的着床部位,使用图像分析系统(KS-400)在子宫系膜三角区的螺旋动脉三个平行层中评估血管内滋养层细胞、纤维蛋白样物质、内皮细胞和平滑肌细胞的存在情况。在另一组动物中,通过多普勒测量子宫动脉和弓形动脉的收缩期峰值和舒张末期速度,并计算阻力指数(RI)。在PE和RM大鼠中,整个子宫系膜三角区的血管内滋养层细胞和血管纤维蛋白样沉积物明显多于C组。各组管腔周围平滑肌总量无差异,但在PE和RM组中,滋养层覆盖的部分轮廓中平滑肌明显更多。PE和RM组总管腔轮廓中的CD31阳性内皮细胞明显少于C组,但在滋养层覆盖的部分轮廓中,两个TGR组的残留内皮细胞更多。三层比较表明,PE和RM组的浸润均比C组更深。通过对子宫近端动脉的多普勒分析,发现PE组和RM组的RI明显低于C组。在弓形动脉中,PE组的RI明显低于RM组和C组。我们得出结论,在这个转基因PE大鼠模型中,妊娠第18天时螺旋动脉的血管内浸润更深,子宫动脉的RI降低。

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