Kucuk Mutlu, Ugur Yilmaz Canan, Orhan Nurcan, Ahishali Bulent, Arican Nadir, Elmas Imdat, Gürses Candan, Kaya Mehmet
Department of Laboratory Animals Science, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Department of Laboratory Animals Science, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey; Department of Pharmaceutical Bioscience, Biomedical Centrum, Uppsala University, Uppsala, Sweden.
J Stroke Cerebrovasc Dis. 2018 Dec;27(12):3411-3418. doi: 10.1016/j.jstrokecerebrovasdis.2018.08.003. Epub 2018 Sep 12.
Preeclampsia is a disorder characterized by high blood pressure and often proteinuria during pregnancy. It is known that a subseptic dose of bacterial lipopolysaccharide (LPS) induces production of proinflammatory cytokines, and possibly increasing the risk for developing preeclampsia. We investigated the effects of LPS on the blood-brain barrier (BBB) integrity in pregnant rats with N(omega)-nitro-l-arginine methyl ester (L-NAME) induced preeclampsia.
Starting from the 10th day of gestation, pregnant rats were given L-NAME for 10 days to produce hypertension and proteinuria. Animals were then treated with a single injection of LPS on the 19th day of pregnancy. Arterial blood pressure and proteinuria were measured on the day of the experiment, which was 24 hours after the LPS injection. The BBB integrity was assessed by using Evans blue (EB) and horseradish peroxidase (HRP) tracers.
Proteinuria was observed in varying degrees, and the arterial blood pressure increased in L-NAME-treated pregnant rats (P < .01). The overall brain EB content did not increase in these preeclamptic rats when compared to pregnant animals, and LPS treatment also did not change EB content. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in the capillary endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated with L-NAME (P < .01). However, LPS did not change the amounts of HRP that mainly accumulated in brain capillary endothelial cells of these animals.
Our results suggest that, in this experimental setting, LPS does not change the severity of BBB disruption observed in preeclamptic animals.
子痫前期是一种在孕期以高血压并常伴有蛋白尿为特征的病症。已知亚败血症剂量的细菌脂多糖（LPS）可诱导促炎细胞因子的产生，并可能增加患子痫前期的风险。我们研究了LPS对N（ω）-硝基-L-精氨酸甲酯（L-NAME）诱导的子痫前期孕鼠血脑屏障（BBB）完整性的影响。
从妊娠第10天开始，给孕鼠注射L-NAME，持续10天以诱发高血压和蛋白尿。然后在妊娠第19天对动物单次注射LPS。在LPS注射24小时后的实验当天测量动脉血压和蛋白尿。通过使用伊文思蓝（EB）和辣根过氧化物酶（HRP）示踪剂评估BBB的完整性。
在接受L-NAME治疗的孕鼠中观察到不同程度的蛋白尿，且动脉血压升高（P <.01）。与正常孕鼠相比，这些子痫前期大鼠的全脑EB含量并未增加，LPS处理也未改变EB含量。超微结构观察发现，在接受L-NAME治疗的孕鼠大脑皮质和海马体的毛细血管内皮细胞中，经常可见含有HRP反应产物的囊泡（P <.01）。然而，LPS并未改变主要积聚在这些动物脑毛细血管内皮细胞中的HRP量。
我们的结果表明，在本实验条件下，LPS不会改变子痫前期动物中观察到的BBB破坏的严重程度。
