硫酸镁对子痫前期大鼠胎盘组织氧化应激损伤和低氧诱导因子1α表达水平的影响

Effects of magnesium sulfate on oxidative stress injury and hypoxia⁃inducible factor 1αexpression level in placental tissues of preeclampsia rats

目的探讨硫酸镁对子痫前期大鼠胎盘组织氧化应激损伤及低氧诱导因子1α(HIF⁃1α)表达水平的影响。方法将30只SD大鼠随机分为空白对照组、子痫前期(PE)组、硫酸镁组各10只,除空白对照组外,均采用内毒素构建PE大鼠模型,硫酸镁组给予硫酸镁80 mg/kg腹腔注射干预,空白对照组、PE组注射同等剂量生理盐水,孕21 d行剖宫产,分离胎盘组织,采用荧光定量聚合酶链反应法(RT⁃PCR)法测定胎盘组织HIF⁃1α水平,并采用紫外比色法测定胎盘组谷胱甘肽过氧化物酶(GPX)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平,采用组织匀浆法测定胎盘组织活性氧(ROS)水平。结果(1)妊娠10 d,各组血压、24 h尿蛋白定量比较差异无统计学意义(均P>0.05),妊娠15 d、妊娠21 d,空白对照组血压、24 h尿蛋白定量无明显变化,PE组、硫酸镁组上述指标均上升(均P<0.05),与同组妊娠10 d比较差异有统计学意义(均P<0.05),且高于空白对照组同时间段血压、24 h尿蛋白定量(均P<0.05),硫酸镁组妊娠21 d血压及24 h尿蛋白定量均低于PE组(均P<0.05);(2)PE组大鼠胎盘质量、仔鼠体质量及身长均低于空白对照组(均P<0.05),硫酸镁组大鼠胎盘质量、仔鼠体质量及身长高于PE组(均P<0.05);(3)PE组、硫酸镁组胎盘组织GPX、SOD均低于空白对照组(均P<0.05),MDA、ROS、HIF⁃1αmRNA高于空白对照组(均P<0.05),硫酸镁组胎盘组织GPX、SOD高于PE组,MDA、ROS、HIF⁃1αmRNA低于PE组(均P<0.05)。结论PE大鼠伴明显氧化应激损伤,且胎盘组织HIF⁃1αmRNA水平较高,而给予硫酸镁干预可减轻其氧化应激损伤,下调HIF⁃1αmRNA表达。

Objective To investigate the effects of magnesium sulfate on oxidative stress injury and hypoxia⁃inducible factor 1α(HIF⁃1α)expression level in placental tissues of preeclampsia rats.Methods Thirty SD rats were randomly divided into the blank control group,preeclampsia(PE)group,and magnesium sulfate group(n=10 each).Except for the blank control group,endotoxin was used in the other groups to establish PE rat model.The magnesium sulfate group was given intraperitoneal injection of 80 mg/kg magnesium sulfate.The blank control group and PE group were injected with the same dose of normal saline.The cesarean section was performed at 21 d after pregnancy,and the placenta tissues were isolated.The level of HIF⁃1αin the placenta tissues was measured by real⁃time fluorescence quantitative polymerase chain reaction(RT⁃PCR)method.The levels of glutathione peroxidase(GPX),malondialdehyde(MDA)and superoxide dismutase(SOD)in the placenta tissues were determined by ultraviolet colorimetry.The tissue homogenate method was used to determine the reactive oxygen species(ROS)level in the placenta tissues.Results(1)At 10 d after the pregnancy,there were no statistically significant differences in the blood pressure and 24 h urinary protein quantification between the groups(all P>0.05).At 15 d and 21 d after the pregnancy,there were no significant change in the blood pressure and 24 h urinary protein quantification in the blank control group,whereas the above indexes increased in the PE group and magnesium sulfate group(all P<0.05),and there were statistically significant differences compared with those at 10 d after pregnancy in the same group(all P<0.05).The blood pressure and 24 h urine protein quantification in the PE group and magnesium sulfate group were higher than those in the blank control group during the same time period(all P<0.05).The blood pressure and 24 h urine protein quantification in the magnesium sulfate group were lower than those in the PE group(all P<0.05).(2)The placenta weight,and weight and length of newborn rats in the PE group were lower than those in the blank control group(all P<0.05),whereas the indexes in the magnesium sulfate group were higher than those in the PE group(all P<0.05).(3)The levels of GPX and SOD in placental tissues in the PE group and magnesium sulfate group were lower than those in the blank control group(all P<0.05),whereas the levels of MDA,ROS and HIF⁃1αmRNA were higher than those in the blank control group(all P<0.05).The levels of GPX and SOD in the magnesium sulfate group were higher than those in the PE group,whereas the levels of MDA,ROS and HIF⁃1αmRNA were lower than those in the PE group(all P<0.05).Conclusion PE rats show significant oxidative stress injury,and the mRNA level of HIF⁃1αis significantly high in placenta tissues.The intervention with magnesium sulfate may reduce oxidative stress injury and down⁃regulate the mRNA expression level of HIF⁃1α.