丹参川芎嗪对妊娠期高血压疾病大鼠的疗效分析

Efficacy analysis of Salvia-ligustrazine on rats with pregnancy induced hypertension syndrome.

目的:探讨丹参川芎嗪对妊娠期高血压疾病(HDP)大鼠的疗效及其可能机制。方法:将孕鼠随机分为4组,即正常妊娠对照组(空白对照组)、HDP对照组(模型对照组)、HDP硫酸镁治疗组(硫酸镁组)和HDP丹参川芎嗪治疗组(丹参川芎嗪组),每组各20只。妊娠14天(d14)时,用亚硝基左旋精氛酸甲酯(L-NAME)尾静脉注射建立大鼠HDP模型。d14开始,空白对照组和模型对照组孕鼠给予生理盐水,硫酸镁组和丹参川芎嗪组孕鼠分别采用丹参川芎嗪和硫酸镁治疗,持续3天。通过大鼠套尾法进行血压测量、24h尿蛋白测定;观察各组新生鼠的身长、体重、死胎率、后肢畸形率和胎盘重量;FCM法检测各组胎盘细胞凋亡率;Western blot法检测胎盘细胞cyclin B1和p21蛋白的表达。结果:妊娠晚期给予L-NAME,成功建立大鼠HDP,孕鼠血压、尿蛋白显著增加;新生鼠身长、体重和胎盘重量显著降低;死胎及畸形发生率增加;胎盘组织的细胞凋亡率显著增高;cyclinB1蛋白表达显著减少,p21蛋白表达显著增高。与模型对照组比较,经丹参川芎嗪和硫酸镁治疗后,孕鼠血压、尿蛋白均显著降低(P<0.05);孕鼠胎盘重量,新生鼠身长和体重均显著提高(P<0.05);死胎率和新生鼠后肢畸形显著降低(P<0.05);孕鼠胎盘细胞的凋亡率显著降低(P<0.05);cyclin B1蛋白表达激活,而p21蛋白表达下调。与硫酸镁组比较,丹参川芎嗪组的死胎率和新生鼠后肢畸形率均显著降低(P<0.05)。结论:丹参川芎嗪能降低HDP孕鼠的血压、尿蛋白,减少幼鼠死胎及畸形发生率,其可能与丹参川芎嗪激活胎盘cyclin B1蛋白和下调p21蛋白表达,进而降低胎盘细胞凋亡率有关。

Objective： To evaluate the effect and possible mechanism of Salvia-ligustrazine on rats of Hypertensive Disorders in Syndrome（HDP）.Methods： The pregnant rats were randomly divided into control group,model group,magnesium sulfate group,and salvia-ligustrazine group,and every group had 20 rats.The model rats of HPD were made by administration of Nitroso-methyl L refined atmosphere（L-NAME） via caudal vein when the rats had been pregnant for 14d,various experimental agents had been administrated to every group for three days.Blood pressure were measured by the tail-cuff method,urinary protein,placental weight,body length,body weight and hind limb deformity rate of newborn rats were measured,apoptotic rate of placental cells of all experimental rats was detected by FCM,and cyclin B1 protein and p21 protein were analyzed by western blot.Results： The model rats of HPD were established successfully by administration of L-NAME.The blood pressure and urinary protein of pregnant rats were increased when L-NAME had been administrated;body length,body weight of newborn rats and placental weight significantly decreased.Fetal death and deformational rate increased,apoptotic rate of placental cells significantly increased,concomitant with down regulation of cyclinB1 protein and activation of p21 protein.Comparing with model group,the blood pressure and urinary protein of pregnant rats treated with magnesium sulfate and salvia-ligustrazine significantly decreased respectively（P0.05）,placental weight of pregnant rats,body length and body weight of newborn rats significantly increased（P0.05）,fetal death and hind limb deformational rate significantly decreased（P0.05）,apoptotic rate of placental cells significantly decreased（P0.05）,concomitant with activation of cyclinB1 protein and down regulation of p21 protein.Comparing with magnesium sulfate group,fetal death and hind limb deformation rate of salvia-ligustrazine group significantly decreased（P0.05）.Conclusions： Salvia-ligustrazine could decrease blood pressure and urinary protein of rats of HDP,reduce the deformity rate and fetal death rate,which may be related to activation of cyclin B1 protein and down-regulating p21 protein and then reduce placental cells apoptosis.