丹参川芎嗪与硫酸镁对妊娠期高血压疾病大鼠的治疗效果及对胎盘组织缺氧诱导因子-1α、可溶性血管内皮生长因子受体-1表达的影响

Effect of salvia miltiorrhiza and ligustrazine and magnesium sulfate on the recovery and expression of HIF-1αand sFLT-1 in placenta of HDCP rats

目的:探讨丹参川芎嗪与硫酸镁对妊娠期高血压疾病(HDCP)大鼠的治疗效果及对胎盘组织中缺氧诱导因子-1α(HIF-1α)、可溶性血管内皮生长因子受体-1(sFLT-1)的影响。方法:建立HDCP模型,随机分为HDCP组、硫酸镁组、丹参组,分别给予HDCP大鼠腹腔注射0.9%生理盐水、100 mg/kg硫酸镁、丹参川芎嗪,对照组为正常妊娠组给予腹腔注射0.9%生理盐水,记录胎鼠发育情况;对胎盘组织进行H-E染色;RT-PCR、免疫印迹检测胎盘组织中HIF-1α、sFLT-1 mRNA及蛋白水平。结果:与对照组相比,其余3组大鼠血压、尿蛋白值均升高,说明妊娠期高血压建模成功。与HDCP组相比,硫酸镁组、丹参组大鼠用药后血压、尿蛋白值下降明显。对照组胎鼠及胎盘质量均高于HDCP组、硫酸镁组、丹参组;与HDCP组比较,硫酸镁组、丹参组胎鼠、胎盘质量明显增加。对照组未出现死胎;与HDCP组比较,硫酸镁组、丹参组死胎率下降。对照组胎盘结构正常,细胞完整;HDCP组出现胎盘结构萎缩,绒毛数目显著减少,有坏死的绒毛纤维素样出现,细胞异常增殖;丹参组胎盘组织结构异常减轻,坏死绒毛纤维素样减少且优于硫酸镁组。与对照组比较,HDCP组胎盘组织HIF-1α、sFLT-1 mRNA及蛋白水平明显升高;与HDCP组比较,硫酸镁、丹参组上述指标水平明显下降,且丹参组低于硫酸镁组。结论;丹参川芎嗪与硫酸镁均对妊娠期高血压大鼠有明显治疗作用,胎鼠妊娠结局较好,丹参川芎嗪效果更佳,其作用机制可能与降低大鼠胎盘HIF-1α、sFLT-1表达有关。

Objective:To explore the therapeutic effects of salvia miltiorrhiza and ligustrazine and magnesium sulfate on hypertensive disorders complicating pregnancy(HDCP)in rats and on expression of hypoxia-inducible factor-1α(HIF-1α)and soluble vascular endothelial growth factor receptor-1(sFLT-1).Methods:Pregnancy-induced hypertension syndrome models were established among normal pregnant rats,and they were randomly divided into intraperitoneal injection of 0.9%saline),magnesium sulfate group(intraperitoneal injection of 100 mg/kg of magnesium sulfate),and salvia miltiorrhiza group(HDCP rats were given intraperitoneal injection of salvia miltiorrhiza and ligustrazine),and the remaining were the control group(intraperitoneal injection of 0.9%normal saline).The development of the fetus were recorded.H-E stained placenta tissue.RT-PCR and Western blotting methods were used to detect levels of HIF-1α,sFLT-1 mRNA and protein in placental tissues.Results:Compared with control group,blood pressure and urine protein values were elevated in the other three groups of rats,which showed that gestational hypertension HDCP model was successful.Compared with the HDCP group,blood pressure and urine protein value decreased significantly in the magnesium sulfate group and salvia miltiorrhiza group.The body mass of fetal rats,placenta were higher in the control group than HDCP group,the magnesium sulfate group,and salvia miltiorrhiza group.The control group did not appear dead fetus.Compared with the HDCP group,fetal rats and placenta body mass in the magnesium sulfate group,salvia miltiorrhiza group increased significantly.In the control group,the placenta structure was normal and the cells were intact.In the HDCP group,the placenta structure was atrophy,the number of villi was significantly reduced,the necrotic villi cellulose appeared,and the cell proliferation was abnormal.In the salvia miltiorrhiza group,the abnormal tissue structure and the necrotic villi cellulose were reduced,which was better than that in the magnesium sulfate group.Compared with the control group,the mRNA and protein levels of HIF-1αand sFLT-1 in the HDCP group were significantly increased.Compared,with the HDCP group,the above indexes in the magnesium sulfate and salvia miltiopsis group were significantly decreased,but in the salvia miltiorrhiza group was lower than magnesium sulfate group.Conclusion:Both salvia miltiorrhiza and ligustrazine and magnesium sulfate have obvious therapeutic effects on HDCP rats with gestational hypertension,the pregnancy outcome of fetal rats is better.The former is better.The mechanism of action may be related to the decrease of HIF-1αand sFLT-1 expression in rat placenta.