丹参素治疗妊娠期高血压大鼠效果及机制探讨  

Effect and mechanism of Danshensu on pregnancy-induced hypertension rats

作　　者：刘莎莎 孙国强[1] 吴利荣[2] LIU Shasha;SUN Guoqiang;WU Lirong(Maternal and Child Health Hospital of Hubei Province,Wuhan 430070,China;不详)

机构地区：[1]湖北省妇幼保健院,武汉430070 [2]武汉科技大学附属汉阳医院

出　　处：《山东医药》2021年第8期46-50,共5页Shandong Medical Journal

基　　金：湖北省自然科学基金项目(WJ2019M227)。

摘　　要：目的观察丹参素治疗妊娠期高血压(PIH)大鼠的效果,并探讨其机制。方法SD孕鼠随机分为正常组,PIH组,丹参素低、中、高剂量组,阳性对照组,每组10只。除正常组外,其余各组均于妊娠第14天建立PIH模型;妊娠第18天,丹参素低、中、高剂量组和阳性对照组分别经尾部肌肉注射5、10、20 mg/kg的丹参素和100 mg/kg的硫酸镁,1次/天,共给药3 d;PIH组只造模不给予其他药物;正常组经尾静脉注射生理盐水。于妊娠第20天检测24 h尿蛋白量;妊娠第21天检测大鼠尾动脉收缩压;对各组大鼠行剖宫术,测定胎鼠身长、体质量,统计死胎率、畸形率;采用HE染色观察胎盘组织绒毛形态变化;采用ELISA法检测血清一氧化氮(NO),Western blotting法检测胎盘组织中的可溶性血管内皮生长因子受体1(sFlt-1)、胎盘生长因子(PLGF)、磷酸化一氧化氮合酶(p-eNOs)蛋白。结果造模各组大鼠血压、24 h尿蛋白量、胎鼠畸形率、胎鼠死亡率、胎盘组织sFlt-1蛋白表达均高于正常组,胎盘质量、胎鼠体质量、体长、血清NO水平、胎盘组织PLGF和p-eNOS蛋白表达低于正常组(P均<0.05)。PIH组、阳性对照组及丹参素低、中、高剂量组的血压、24 h尿蛋白量依次降低(P均<0.05)。PIH组、阳性对照组、丹参素中剂量组、丹参素高剂量组大鼠胎盘质量、胎鼠体质量、体长依次增高,胎鼠畸形率、胎鼠死亡率、胎盘组织sFlt-1蛋白表达依次降低,血清NO水平、胎盘组织PLGF和p-eNOS蛋白表达依次升高(P均<0.05)。丹参素各组各项观察指标两两相比,P均<0.05。与PIH组相比,丹参素低、中、高剂量组及阳性对照组大鼠胎盘组织绒毛数目减少、结构萎缩等病理损伤程度减轻。结论丹参素可降低PIH大鼠血压,其对PIH的治疗作用可能与抑制胎盘组织sFlt-1表达、上调PLGF表达,提高胎盘组织eNOs活性和血清NO合成,改善胎盘血管功能有关。Objective To observe the effect of Danshensu on pregnancy-induced hypertension(PIH)rats and to investigate the mechanism.Methods SD pregnant rats were randomly divided into the control group,PIH group,lowdose(5 mg/kg),medium-dose(10 mg/kg),high-dose(20 mg/kg)Danshensu groups,and positive control group(100 mg/kg).Except the control group,the PIH models were established on the 14th day of pregnancy in all the other groups;on the 18th day of pregnancy,corresponding doses of Danshensu were given by tail intramuscular injection,once a day,for a total of 3 days;the models were made in the PIH group without drug treatment.On the 20th day of pregnancy,the 24-hour urine protein was measured;on the 21st day of pregnancy,the rats’tail artery systolic blood pressure was measured.We performed cesarean section on rats in each group to measure the body length and weight of fetal rats,and calculated the fetal death rate and deformity rate.The pathological changes of rat placenta were observed by HE staining;the level of serum NO was detected by nitric oxide(NO)kit;the expression levels of soluble fms-like tyrosine kinase-1(sFlt-1),placental growth factor(PLGF),and endothelial nitric oxide synthase(eNOS)protein were detected by Western blotting.Results Compared with the control group,the blood pressure,24-hour urine protein content,the deformity rate,mortality rate and the SFlt-1 protein expression in the placental tissues were higher in the model rats,while the placental mass,body mass of fetal rats,body length,serum NO level,and the PLGF and p-eNOS protein expression levels in the placental tissues were lower(all P<0.05).The blood pressure and 24-hour urine protein in the PIH group,the positive control group,and the low-dose,medium-dose,and high-dose Danshensu groups decreased in turn(all P<0.05).The rat placenta mass,body mass of of fetal rats,and body length increased,the deformity rate,mortality rate,and sFlt-1 protein expression in the placental tissues decreased,and the serum NO level,PLGF and p-eNOS protein expression l

关 键 词：妊娠期高血压 丹参素 可溶性血管内皮生长因子受体1 胎盘生长因子 一氧化氮 血管功能 妊娠结局 

分 类 号：R714.25[医药卫生—妇产科学]