当归多糖对子痫前期大鼠胎盘灌注的影响及机制研究

Effect of Angelica Polysaccharide on Placental Perfusion in Preeclampsia Rats and Its Mechanism

目的:探讨当归多糖对子痫前期(PE)胎盘灌注的影响及可能机制。方法:建立PE大鼠模型,随机分为正常对照组、模型对照组、当归多糖100、200 mg/kg组和硫酸镁270 mg/kg组,各组给予相应药物或等体积5%羧甲基纤维素钠溶液。检测各组孕鼠尾动脉压和尿蛋白含量;观察各组孕鼠妊娠结局;超声造影观察各组胎鼠脐动脉、大脑中动脉和孕鼠子宫动脉搏动指数(PI)、阻力指数(RI)、收缩期峰值流速与舒张期最低流速比值(S/D);HE染色观察胎盘组织病理学变化;免疫荧光染色观察胎盘微血管密度;Western blot法检测胎盘组织血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)蛋白表达。结果:与正常对照组比较,模型对照组胎盘组织明显受损,血管减少,孕鼠孕10 d后尾动脉压和尿蛋白含量、死胎数比例、胎鼠脐动脉、大脑中动脉和孕鼠子宫动脉的PI、RI和S/D升高,胎鼠体质量、微血管密度减少、胎盘VEGF、PLGF蛋白表达降低(P<0.05);与模型对照组比较,当归多糖100、200 mg/kg组和硫酸镁270 mg/kg组胎盘组织病理学变化明显改善,孕10 d后尾动脉压和尿蛋白含量、死胎数比例、胎鼠脐动脉、大脑中动脉和孕鼠子宫动脉的PI、RI和S/D降低,胎鼠体质量、微血管密度升高、胎盘VEGF、PLGF蛋白表达升高(P<0.05)。结论:当归多糖对PE大鼠具有治疗作用,可上调VEGF、PLGF蛋白表达,增加胎盘血流灌注,改善PE症状。

Objective:To investigate the effect of Angelica polysaccharide on placental perfusion in preeclampsia(PE)and its mechanism.Methods:A PE rat model was established,and rats were randomly divided into a normal control group,a model control group,two Angelica polysaccharide groups(100 and 200 mg/kg),and a magnesium sulfate(270 mg/kg)group.All the rats were administrated with corresponding drugs or equal volume of 5%carboxymethyl cellulose sodium solution.The tail arterial pressure and urinary protein content of pregnant rats were detected,and the pregnancy outcomes were observed.The pulsatility index(PI),resistance index(RI),and systolic diastolic ratio(S/D)of the umbilical artery,middle cerebral artery in fetal rats,and uterine artery in pregnant rats were observed by ultrasonic contrast.Hematoxylin-eosin(HE)staining was used to observe placental histopathological changes,and immunofluorescence staining was used to observe placental micro vessel density.Western blot was used to determine the protein expressions of vascular endothelial growth factor(VEGF)and placental growth factor(PLGF)in the placental tissue.Results:As compared with the normal control group,the placental tissue of rats in the model control group was significantly damaged,and the blood vessels were reduced.After 10 d of pregnancy,the tail artery pressure,the content of urine protein,the ratio of fetal mortality,PI,RI,and S/D in the umbilical artery,middle cerebral artery of fetal rats,and uterine artery of pregnant rats in the model control group were increased,while fetal body weight,micro vessel density,and protein expressions of VEGF and PLGF were down-regulated(P<0.05).As compared with the model control group,the histopathological changes in placenta in the Angelica polysaccharide groups(100 and 200 mg/kg)and the magnesium sulfate(270 mg/kg)group were significantly improved.After 10 d of pregnancy,the tail artery pressure,the content of urine protein,the ratio of fetal mortality,PI,RI,and S/D in the umbilical artery,middle cerebral artery of fetal rats,and uterine artery of pregnant rats in the administration groups were decreased,while fetal body weight,micro vessel density,and the protein expressions of VEGF and PLGF were up-regulated(P<0.05).Conclusion:Angelica polysaccharide has the therapeutic effect on PE rats by up-regulating the protein expressions of VEGF and PLGF and increasing the placental blood perfusion.