基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1109-1113.

• 研究论文 • 上一篇    下一篇

普伐他汀激活子痫前期小鼠MAPK抗凋亡信号通路

王芙蓉1, 严谨2, 贺丰杰1*   

  1. 1.陕西中医药大学附属医院 产科, 陕西 咸阳 712000;
    2.陕西中医药大学 第一临床医学院, 陕西 咸阳 712046
  • 收稿日期:2020-06-23 修回日期:2020-08-29 出版日期:2021-08-05 发布日期:2021-07-21
  • 通讯作者: *hefengjie2013@163.com
  • 基金资助:
    国家自然科学基金(81173290)

Pravastatin activates the anti-apoptotic signaling pathway of MAPK in pre-eclampsia mice

WANG Fu-rong1, YAN Jin2, HE Feng-jie1*   

  1. 1. Department of Obstetrics, the Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000;
    2. the First College of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China
  • Received:2020-06-23 Revised:2020-08-29 Online:2021-08-05 Published:2021-07-21
  • Contact: *hefengjie2013@163.com

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。

关键词: 子痫前期, 普伐他汀, sFlt-1, MAPK

Abstract: 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 was significantly 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.

Key words: pre-eclampsia, Pravastatin, sFlt-1, MAPK

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