摘要
目的 探究普伐他汀对子痫前期(PE)大鼠胎盘氧化应激的改善作用机制.方法 将27只子痫前期大鼠随机分为子痫前期组及普伐他汀高、低剂量组,每组9只,10只健康妊娠大鼠为对照组.普伐他汀高、低剂量组分别予普伐他汀每天50、25 mg·kg-1,对照组与PE组注射等量生理盐水.测量血压及24 h尿蛋白;检测大鼠胎盘及胎鼠体质量;检测血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性;比较胎盘组织缺氧诱导因子1α/血红素氧合酶1(HIF-1α/HO-1)通路相关蛋白表达量.结果 与子痫前期组比较,普伐他汀高、低剂量组舒张压(DBP)、收缩压(SBP)、24 h尿蛋白水平均降低,胎鼠体质量、SOD、CAT水平及核因子E2相关因子2(Nrf2)、HIF-1α、HO-1、血管内皮生长因子(VEGF)蛋白表达量均升高(P＜0.05);与普伐他汀低剂量组比较,普伐他汀高剂量组DBP、SBP、24h尿蛋白水平均降低,胎鼠体质量、SOD、CAT水平及Nrf2、HIF-1α、HO-1、VEGF蛋白表达量均升高(P＜0.05).结论 普伐他汀可缓解PE大鼠症状,减轻氧化应激,其作用机制可能与调控HIF-1α/HO-1信号通路有关.
Abstract
Objective To explore the mechanism of pravastatin on improving placental oxidative stress in rats with preeclampsia(PE).Methods 27 PE rats were randomly divided into PE group,high-dose pravastatin group and low-dose pravastatin group,with 9 rats in each group.10 healthy pregnant rats were used as the control group.High-dose pravastatin group and low-dose pravastatin group were given pravastatin 50 mg·kg-1 and 25 mg·kg-1 per day,respectively.The control group and PE group were injected with the equal amount of normal saline.Blood pressure and 24-hour urine protein were measured.Placental and fetal body masses of rats were detected.The activities of serum superoxide dismutase(SOD)and catalase(CAT)were detected.The expression levels of hypoxia inducible factor 1α/heme oxygenase 1(HIF-1α/HO1)pathway related proteins in placental tissue were compared.Results Compared with PE group,in high-dose pravastatin group and low-dose pravastatin group,diastolic blood pressure(DBP),systolic blood pressure(SBP),and 24-hour urinary protein levels decreased,and the body mass,SOD and CAT levels,and the expression levels of nuclear factor E2-related factor 2(Nrf2),HIF-1α,HO-1 and vascular endothelial growth factor(VEGF)increased(P＜0.05).Compared with low-dose pravastatin group,in high-dose pravastatin group,DBP,SBP,and 24-hour urinary protein levels decreased,and the body mass,SOD and CAT levels,and the expression levels of Nrf2,HIF-1α,HO-1 and VEGF increased(P＜0.05).Conclusion Pravastatin can alleviate the symptoms of PE rats,reduce oxidative stress of PE rats,and its mechanism may be related to the regualtion of the HIF-1α/HO-1 signaling pathway.
基金项目
山西省青年科技研究基金(2020021038-3)
大同市重点研发计划(2020070)
维普
万方数据