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

doi:10.3877/cma.j.issn.1673-5250.2015.01.007

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 (1 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. Hippocampal neurons in CA1 region were analyzed for apoptosis by TUNEL assay. Relative expression levels of cysteine aspartic 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 hippocampus in rat brains among three groups (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.

Key words: Pre-eclampsia, Hippocampus, Apoptosis, Magnesium sulfate, Caspase 3

表1 3组大鼠孕期各时间点收缩压变化情况比较(mmHg, ±s)

Table 1 Comparison of the blood pressure change at different time points during pregnancy among three groups (mmHg, ±s)

组别	例数	13 d	15 d	19 d
模型组	6	111.4±4.9	141.2±8.2^a	139.2±9.1^c，d
治疗组	6	109.1±3.9	139.9±7.5^b	119.9±6.8
对照组	6	112.3±4.3	108.5±8.2	110.5±8.2
F值	?	2.876	26.758	165.040
P值	?	0.068	0.000	0.000

表1 3组大鼠孕期各时间点收缩压变化情况比较(mmHg, ±s)

Table 1 Comparison of the blood pressure change at different time points during pregnancy among three groups (mmHg, ±s)

组别	例数	13 d	15 d	19 d
模型组	6	111.4±4.9	141.2±8.2^a	139.2±9.1^c，d
治疗组	6	109.1±3.9	139.9±7.5^b	119.9±6.8
对照组	6	112.3±4.3	108.5±8.2	110.5±8.2
F值	?	2.876	26.758	165.040
P值	?	0.068	0.000	0.000

图1 胎鼠脑海马CA1区TUNEL染色，胎鼠脑海马CA1区神经细胞均出现不同程度的凋亡（TUNEL染色，×400；A：模型组；B：治疗组；C：对照组）

Figure 1 Fetal rat hippocampal CA1 area by TUNEL staining (TUNEL staining, ×400; A: model group; B: treatment group; C: control group)

表2 各组胎鼠脑海马组织CA1区神经细胞凋亡情况比较(个/高倍视野)

Table 2 Comparison of hippocampus of fetal rat(per high power field)

组别	例数	凋亡细胞数
模型组	6	67.9±3.3^{a b}
治疗组	6	30.6±1.6^c
对照组	6	9.6±1.8
F值	?	1 931.4
P值	?	0.000

表2 各组胎鼠脑海马组织CA1区神经细胞凋亡情况比较(个/高倍视野)

Table 2 Comparison of hippocampus of fetal rat(per high power field)

组别	例数	凋亡细胞数
模型组	6	67.9±3.3^{a b}
治疗组	6	30.6±1.6^c
对照组	6	9.6±1.8
F值	?	1 931.4
P值	?	0.000

表3 各组间胎脑海马组织中caspase-3 mRNA相对表达水平比较

Table 3 Comparison of caspase-3 mRNA relative expression levels of hippocampus among three groups

组别	例数	caspase-3 mRNA
模型组	6	2.87±0.32^{a b}
治疗组	6	1.69±0.41^c
对照组	6	1.00±0.22
F值	?	1 687.13
P值	?	0.000

表3 各组间胎脑海马组织中caspase-3 mRNA相对表达水平比较

Table 3 Comparison of caspase-3 mRNA relative expression levels of hippocampus among three groups

组别	例数	caspase-3 mRNA
模型组	6	2.87±0.32^{a b}
治疗组	6	1.69±0.41^c
对照组	6	1.00±0.22
F值	?	1 687.13
P值	?	0.000

图2 胎鼠脑海马CA1区caspase-3免疫组化检测（TAB染色，×400；A：模型组；B：治疗组；对照组）

Figure 2 Immunohistochemistry of caspase-3 of fetal rat brain hippocampal CA1 region (TAB staining, ×400; A：model group; B：treatment group; C:control group)

表4 各组间胎鼠脑海马组织CA1区caspase-3蛋白比较

Table 4 Comparison of caspase-3 protein of hippocampus CA1 area among three groups

组别	样本量	－	＋	＋＋	＋＋＋
模型组	24	0	4	13	7
治疗组	24	0	9	14	1
对照组	24	2	22	0	0
χ²值	?	?	36.057	?	?
P值	?	?	0.000	?	?

表4 各组间胎鼠脑海马组织CA1区caspase-3蛋白比较

Table 4 Comparison of caspase-3 protein of hippocampus CA1 area among three groups

组别	样本量	－	＋	＋＋	＋＋＋
模型组	24	0	4	13	7
治疗组	24	0	9	14	1
对照组	24	2	22	0	0
χ²值	?	?	36.057	?	?
P值	?	?	0.000	?	?

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