丹参川芎嗪注射液对妊娠期高血压大鼠胎盘PLGF和sFLT-1的影响

Effects of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection on placental PLGF and sFLT-1 in hypertensive disorder complicating pregnancy rats

目的 探讨丹参川芎嗪注射液对妊娠期高血压(HDCP)大鼠胎盘生长因子(PLGF)和可溶性血管内皮生长因子受体-1(sFLT-1)的影响。方法 36只HDCP大鼠(孕15 d)随机平分为3组-模型组、硫酸镁组与丹参川芎嗪组,分别给予注射等剂量0.9%氯化钠溶液、硫酸镁、丹参川芎嗪注射液治疗6 d;另取12只受孕成功大鼠作为空白对照组,连续6 d注射等剂量的0.9%氯化钠溶液。在孕15、21 d采用大鼠无创尾动脉血压监测仪测尾动脉血压,全自动生化分析仪7100定量测定各组大鼠24 h尿蛋白水平,蛋白质印迹法检测胎盘PLGF和sFLT-1的表达情况。结果 模型组、硫酸镁组和丹参川芎嗪组大鼠孕15 d的收缩压、舒张压与24 h尿蛋白比较,差异均无统计学意义(P> 0.05);硫酸镁组与丹参川芎嗪组孕21 d的收缩压与舒张压、24 h尿蛋白低于孕15 d,也低于模型组,丹参川芎嗪组也低于硫酸镁组,差异均有统计学意义(P <0.05)。硫酸镁组与丹参川芎嗪组孕21 d的胎鼠重量均高于模型组,丹参川芎嗪组高于硫酸镁组,差异均有统计学意义(P <0.05)。硫酸镁组与丹参川芎嗪组孕21 d的胎盘PLGF相对表达量均高于模型组,sFLT-1相对表达量均低于模型组,差异均有统计学意义(P <0.05);丹参川芎嗪组PLGF相对表达量高于硫酸镁组,sFLT-1相对表达量低于硫酸镁组,差异均有统计学意义(P <0.05)。结论 丹参川芎嗪注射液在HDCP大鼠中的应用能降低胎盘sFLT-1表达水平,提高PLGF表达水平,从而促进降低血压与尿蛋白含量,提高胎鼠重量。

Objective To investigate the effects of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection on placental growth factor(PLGF)and soluble vascular endothelial growth factor receptor-1(sFLT-1)in hypertensive rats during pregnancy.Methods Thirty-six cases of pregnancy-induced hypertensive rats(15 days pregnant)were equally randomly divided into three groups-model group,magnesium sulfate group and Salviae Miltiorrhizae and Ligustrazine Hydrochloride group.There were given equal-dose 0.9%sodium chloride solution,magnesium sulfate,and Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection were injected for 6 days.Another 12 successfully conceived rats were taken as the blank control group,and were injected with the same dose of 0.9%sodium chloride solution for 6 consecutive days.At the 15th and 21st day of pregnancy,non-invasive tail artery blood pressure monitor was used to measure tail artery blood pressure,automatic biochemical analyzer 7100 was used to quantitatively measure the 24 h urine protein level of rats in each group,and Western blotting was used to detect the expression of placental PLGF and sFLT-1.Results There was no significant difference in systolic blood pressure,diastolic blood pressure and 24 h urine protein among the model group,magnesium sulfate group and Salviae Miltiorrhizae and Ligustrazine Hydrochloride group at 15 days of gestation(P>0.05);the systolic blood pressure,diastolic blood pressure and 24 h urine protein at 21 days of pregnancy in the magnesium sulfate group and the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group were lower than those at the 15th day of pregnancy,were lower than the model group,and the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group were also lower than the magnesium sulfate group,the differences were statistically significant(P<0.05).The weight of fetuses in the magnesium sulfate group and the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group at 21 days of pregnancy were higher than that of the model group,and the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group were higher than that of the magnesium sulfate group,the differences were statistically significant(P<0.05).The relative expression levels of PLGF in the placenta of the magnesium sulfate group and the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group at 21 days of pregnancy were higher than that of the model group,the relative expression of sFLT-1 was lower than that of the model group,the differences were statistically significant(P<0.05);the relative expression of PLGF in the Salviae Miltiorrhizae and Ligustrazine Hydrochloride group was higher than that of the magnesium sulfate group,and the relative expression of sFLT-1 was lower than that of magnesium sulfate group,the differences were statistically significant(P<0.05).Conclusion The application of Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection in pregnancy-induced hypertensive rats can reduce the expression level of placenta sFLT-1 and increase the expression level of PLGF,thereby promoting the reduction of blood pressure and urine protein content,and increasing the weight of fetal rats.