硫酸镁对先兆子痫大鼠病理模型子代海马神经细胞的保护作用

Effects of magnesium sulfate on the neuroprotection of hippocampus of fetal rats delivered by experimental rats model of preeclampsia

目的探讨硫酸镁（MgSO4）对先兆子痫（PE）大鼠病理模型子代（胎鼠）海马神经细胞的保护作用。方法选择确定妊娠的18只健康Sprague-Dawley（SD）大鼠为研究对象,按照不同处理方式,随机将其分为3组：模型组（n=6,空白对照）、治疗组（n=6,使用MgSO4治疗2d的PE病理模型大鼠）、对照组（n=6,正常妊娠大鼠）。模型组和治疗组大鼠均于孕龄为14d时,采用微量输液泵经尾静脉缓慢注入1.0g/kg脂多糖溶液诱导建立PE大鼠病理模型,治疗组大鼠于终止妊娠前2d使用MgSO4治疗,60~120mg/（kg·d）×2d,模型组大鼠不接受任何治疗。对照组大鼠仅注射2mL生理盐水。3组大鼠均于孕龄为20d时行剖宫产。采用TUNEL法检测胎鼠脑组织神经细胞凋亡情况,实时荧光定量（RT）-聚合酶链反应（PCR）和免疫组化法测定海马组织中半胱氨酸天冬氨酸蛋白酶（caspase）-3的相对表达水平。结果 13组大鼠于孕龄为13d时收缩压比较,差异无统计学意义（F=2.876,P〉0.05）。模型组和治疗组大鼠孕龄为15d时收缩压较对照组升高,并且差异有统计学意义（P〈0.05）。孕龄为19d时治疗组收缩压较模型组降低,并且差异有统计学意义（P〈0.05）。23组胎鼠脑海马组织CA1区神经细胞凋亡比较,差异有统计学意义（F=1 931.4,P〈0.05）。模型组和治疗组胎鼠脑海马组织CA1区凋亡神经细胞数较对照组明显增高,并且差异均有统计学意义（P〈0.05）;治疗组凋亡神经细胞数较模型组减少,并且差异有统计学意义（P〈0.05）。33组胎鼠脑海马组织中caspase-3mRNA相对表达水平比较,差异有统计学意义（F=1 687.13,P=0.000）。模型组和治疗组胎鼠海马组织中caspase-3mRNA相对表达水平均较对照组升高,并且差异有统计学意义（P〈0.05）,治疗组caspase-3mRNA相对表达水平较模型组下降,并且差异有统计学意义（P〈0.05）。结论常规剂量MgSO4在PE胎鼠脑组织中发挥神经保护作用,其作用机制可能与胎鼠大脑caspase-3活性调控相关。

Objective To explore the effects of magnesium sulfate （MgSO4） on the hippocampal neurons of fetal rats which were delivered by pre-eclampsia （PE） experimental model rats. Methods A total of 18 pregnant Sprague-Dawley （SD） rats were included into this study. They were divided into 3 groups according to different treatment methods., model group （n=6, PE experimental model group without any treatment）, treatment group （n = 6, 2-day MgSO4 treatment of PE experimental model rats） and control group （normal pregnant rats）. Model group and treatment group were given low dose lipopolysaccharides （l μg/kg） to induce experimental rats model of PE. Treatment group were managed by MgSO4 60-120 （mg/kg·d） for 2 days before the caesarean birth at the 20th day of pregnancy. Hippoeampal neurons in CA1 region were analyzed for apoptosis by TUNEL assay. Relative expression levels of cysteine aspartie proteases （caspase）3 of hippocampus in fetal rats were detected by real-time （RT）-PCR and immunohistochemistry. Results ①There was no significant difference on systolic blood pressure at 13th day during pregnancy among three groups （F=2. 876, P〉0. 05）. The systolic blood pressure of model group and treatment group were higher than that of control group on the 15th day during the pregnancy, with significant differences （P〈0.05）, and the systolic blood pressure of treatment group was lower than than of model group on 19th day during the pregnancy with significant difference （P〈0.05）. ②There was no significant difference on neuronal apoptosis of CA1 region of hippoeampus in rat brains among threegroups （F=1 931.4,P〈0. 05）. The number of neuronal apoptosis of CA1 region of neuronal apoptosis in rat brains of model group and treatment group were higher than that of control group （P〈0.05）, and the number of neuronal apoptosis of CA1 region of neuronal apoptosis in rat brains of treatment group was lower than that of model group （P〈0.05）.③ There was no significant difference on the relative expression levels of caspase-3 mRNA of hippocampus in rat brains among three groups （F= 1 687. 13, P= 0. 000）. The relative expression of caspase-3 mRNA of hippocampus in rat brains of model group and treatment group were higher than that of control group （P〈 0. 05）, and the relative expression of caspase-3 mRNA of hippocampus in rat brains of treatment group was lower than that of control group （P〈 0. 05 ）. Conclusions Administration of regular dose of MgSO4 treatment may play a neuroprotective role in the brain of fetal rats who were delivered by experimental rats model of PE and its mechanism may be related to the regulation of fetal brain caspase-3.