摘要
目的探究普伐他汀对子痫前期(PE)小鼠胎盘组织中抗凋亡路径的影响。方法将妊娠第9天的ICR小鼠随机分为:对照组(Con)未经任何干预;PE模型组(PE)经尾静脉注射携带sFlt-1片段的腺病毒(Adv-sFlt-1);治疗组(PE+Pravastatin)从第9天开始按体质量喂灌普伐他汀[Pravastatin,5 mg/(kg·d)]。妊娠第19天,收集心脏血液和胎盘。酶联免疫吸附试验(ELISA)测定血清sFlt-1水平。免疫印迹检测胎盘组织激活转录因子-2(ATF-2)、细胞外调节蛋白激酶(ERK)1/2、热休克蛋白(HSP)27、p38 MAPK、信号传导及转录激活蛋白(STAT)3及p53蛋白的磷酸化水平。结果PE模型组小鼠血清sFlt-1水平为(95.73±8.44)ng/mL,显著高于对照组小鼠的(55.32±5.66)ng/mL(P<0.05);胎盘组织ATF-2、p38、ERK、HSP27和STAT3蛋白的磷酸化水平均显著低于对照组(P<0.05);经过普伐他汀治疗后,sFlt-1浓度显著下降,胎盘组织ATF-2、p38、ERK、HSP27和STAT3蛋白的磷酸化水平均显著上升(P<0.05)。结论普伐他汀对PE的治疗作用与激活MAPK通路的抗凋亡路径有关。
Objective To investigate the effect of Pravastatin on the pro-survival/anti-apoptotic pathway in placental tissue of Pre-eclampsia(PE)mice.Methods ICR mice with 8 days of gestation were randomly divided into:control group(Con)without any intervention;PE model group(PE)injected with adenovirus carrying sFlt-1 fragment(Adv-sFlt-1)via tail vein;Treatment group(PE+Pravastatin)was given Pravastatin(Pravastatin,5 mg/(kg·d),since the 9th day of gestation.On the 19th day,heart blood and placenta were collected then serum sFlt-1 level was measured by ELISA method.Western blot was used to measure activating transcription factor-2(ATF-2),extracellular regulated protein kinases(ERK)1/2,heat shock protein(HSP)27,p38 MAPK,signal transducer and activator of transcription(STAT)3 and phosphorylation of p53 protein in the placental tissue.Results The serum sFlt-1 level of the PE model group was(95.73±8.44)ng/mL,which wassignificantly higher than that of the control group(55.32±5.66)ng/mL,and the phosphorylation level of ATF-2,p38,ERK,HSP27 and STAT3 protein in the placenta tissue was significantly lower than that of the control group(P<0.05).After pravastatin treatment,the concentration of sFlt-1 decreased significantly,and the phosphorylation level of ATF-2,p38,ERK,HSP27 and STAT3 protein in the placenta tissue increased significantly(P<0.05).Conclusions The therapeutic effect of Pravastatin on PE is related to the pro-survival/anti-apoptotic pathway that activates the MAPK pathway.
作者
王芙蓉
严谨
贺丰杰
WANG Fu-rong;YAN Jin;HE Feng-jie(Department of Obstetrics, the Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000;the First College of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China)
出处
《基础医学与临床》
2021年第8期1109-1113,共5页
Basic and Clinical Medicine
基金
国家自然科学基金(81173290)。
