丹参素对妊娠高血压大鼠妊娠结局的影响

Effects of danshensu on pregnancy outcome and placenta tissues of pregnancy rats with hypertension

目的探究丹参素对妊娠高血压大鼠妊娠结局及胎盘组织胎盘生长因子(PLGF)、p21及细胞周期素B1(cyclinB1)蛋白表达的影响。方法用皮下注射L-精氨酸甲酯(L-NAME)建立妊娠高血压大鼠模型;将60只孕鼠随机分为对照组、模型组、实验组及阳性对照组,每组15只。妊娠第17天起,实验组以尾静脉注射每日40 mg·kg^(-1)丹参素溶液,阳性对照组肌肉注射每日100 mg·kg^(-1)硫酸镁,对照组及模型组则尾静脉注射等量的生理盐水,各组均连续干预至妊娠第20天。分别于妊娠第17和20天用血压测量仪和邻苯三酚红法分别检测各组大鼠尾静脉压及24 h尿蛋白水平;于妊娠第21天剖腹取胎,统计各组妊娠结局;用蛋白免疫印迹法检测各组大鼠胎盘组织中胎盘生长因子(PLGF)、p21、细胞周期素B1(cyclinB1)蛋白表达水平。结果对照组、模型组、实验组及阳性对照组妊娠第17天尾静脉压分别为(102.09±4.21),(136.12±3.99),(135.87±4.02),(136.01±3.79)mmHg;第20天尾静脉压分别为(102.13±3.97),(136.24±3.95),(121.13±2.97),(122.85±3.01)mmHg;第17天大鼠24 h尿蛋白含量分别为(171.06±33.15),(633.21±49.87),(629.86±58.23),(628.97±61.20)mg·L^(-1);第20天大鼠24 h尿蛋白含量分别为(175.38±40.03),(637.96±58.15),(428.21±60.12),(445.37±59.64)mg·L^(-1);大鼠胎盘重量分别是(0.63±0.12),(0.45±0.13),(0.56±0.10),(0.53±0.11)g;胎鼠质量分别是(5.39±0.13),(4.05±0.09),(4.63±0.12),(4.58±0.14)g;PLGF蛋白相对表达量分别为0.31±0.07,0.11±0.05,1.19±0.12,1.05±0.10;p21蛋白相对表达量分别为0.41±0.11,1.38±0.07,0.81±0.11,0.97±0.09;cyclinB1蛋白相对表达量分别为0.94±0.13,0.21±0.07,0.61±0.11,0.57±0.09。模型组与对照组比较,差异均有统计学意义(均P<0.05);实验组及阳性对照组分别与模型组比较,差异均有统计学意义(均P<0.05)。结论丹参素可有效降低妊娠高血压大鼠血压,改善其妊娠结局,其作用机制可能与下调胎盘组织p21蛋白表达及上调胎盘组织PLGF及cyclinB1蛋白表达相关。

Objective To explore the effect of danshensu on pregnancy outcome and the expression of placenta growth factor(PLGF),p21 and cyclinB1 protein in pregnancy rats with hypertension.Methods The model of pregnancy induced hypertension was established by subcutaneous injection of L-arginine methyl ester(L-NAME).A total of 60 SD pregnant rats were equally divided into four groups:the control,model,test and positive control,15 in each group.Pregnancy-induced hypertension(PIH)rat models were established in the rats except the control group.Danshensu solution was administrated in rats from the test group and magnesium sulfate was administrated in positive control group.Normal saline was injected into the rats from the control group and model group.The inventions were stared at the 17 thd of pregnancy and ended at the 20 thd of pregnancy.The venous pressure and 24 h urine protein were measured by blood pressure meter and pyrogallol red method.The pregnancy outcomes of each group were statistically analyzed.The expression of placental growth factor(PLGF),p21、cyclinB1 in the placenta tissue were measured by Western blot assay.Results On the 17 thd of gestation,the venous pressure of the control group,the model group,the test group and the positive control group were(102.09±4.21),(136.12±3.99),(135.87±4.02),(136.01±3.79)mmH g,respectively;on 20 thd of gestation,the venous pressure of the control group,the model group,the test group and the positive control group were(102.13±3.97),(136.24±3.95),(121.13±2.97),(122.85±3.01)mmH g,respectively;on the 17 thd,the 24-hour urinary protein content of rats were(171.06±33.15),(633.21±49.87),(629.86±58.23),(628.97±61.20)mg·L^(-1),respectively;on the20 thd,the 24-hour urinary protein content of rats were(175.38±40.03),(637.96±58.15),(428.21±60.12),(445.37±59.64)mg·L^(-1) respectively;the placental weight were(0.63±0.12),(0.45±0.13),(0.56±0.10),(0.53±0.11)g respectively;the neonatal rat body mass were(5.39±0.13),(4.05±0.09),(4.63±0.12),(4.58±0.14)g respectively;the relative expression of PLGF protein were 0.31±0.07,0.11±0.05,1.19±0.12,1.05±0.10;the relative expression of p21 protein were 0.41±0.11,1.38±0.07,0.81±0.11,0.97±0.09;the relative expression of cyclinB1 protein were 0.94±0.13,0.21±0.07,0.61±0.11,0.57±0.09.Compared between the model group and the control group,the differences were significant(all P<0.05).There were statistically significant differences between the test/positive control group and the model group in the above indicators(P<0.05).Conclusion Danshensu could reduce blood pressure and improve the pregnancy outcome of pregnancy rats with hypertension,the potential mechanism maybe related to the down-regulation of p21 protein and the up-regulation of PLGF and cyclinB1 protein in placenta tissue.