硫酸镁对胎儿生长受限孕鼠胎盘组织半胱氨酸天冬氨酸蛋白酶3表达的影响

目的探讨硫酸镁对胎儿生长受限(FGR)孕鼠胎盘组织半胱氨酸天冬氨酸蛋白酶3(caspase-3)表达的影响,及硫酸镁治疗FGR的机理。方法烟熏法构建FGR模型。实验对象分为对照组(10只)、治疗组(18只)、FGR组(10只)。治疗组中低剂量(硫酸镁300 mg／kg)治疗10只、高剂量(硫酸镁600 mg／kg)治疗8只,皮下注射给药。络合指示剂方法测孕鼠血清Mg2+(血镁)浓度。物理测量胎鼠的各项生理指标。链霉菌抗生物素蛋白-过氧化物酶连接(SP)法及RT-PCR法检测胎盘组织caspase-3的表达情况。结果(1)FGR组孕鼠血镁浓度为(0．55±0．03)mmol／L,高、低剂量治疗组孕鼠血镁浓度分别为(0．72±0．13)、(0．61±0．03)mmol／L,高、低剂量治疗组分别与FGR组比较,差异均有统计学意义(P<0．01)。(2)FGR组孕鼠胎盘重量为(0．63±0．05)g,其胎鼠体重为(2．95±0．46)g,高剂量治疗组分别为(0．80±0．16)、(3．58±0．10)g,两组分别比较,差异均有统计学意义(P<0．05、P<0．01)。(3)FGR组胎盘组织caspase-3 mRNA表达量为0．626±0．036,其蛋白表达量为199．5±4．7,高剂量治疗组分别为0．361±0．030、183．0±3．3,差异均有统计学意义(P< 0．05),低剂量治疗组caspase-3 mRNA表达量为0．525±0．029,与高剂量治疗组比较,差异也有统计学意义(P<0．05)。(4)孕鼠血镁浓度与胎鼠重量、胎盘组织caspase-3 mRNA及蛋白表达量有显著相关性(r=0．899,P=0．038;r=-0．747,P=0．033;r=-0．915,P=0．001)。结论硫酸镁能降低胎盘组织caspase-3 mRNA及蛋白表达,硫酸镁可能通过抑制胎盘caspase-3的表达,减少胎盘滋养细胞、血管内皮细胞等功能细胞的凋亡,从而改善FGR胎鼠的低体重现象。

Effect of magnesium sulfate on fetal rats of fetal growth retardation and its relation with expression of caspase-3 on the placenta of maternal rat

OBJECTIVE: To investigate the effect of magnesium sulfate on the fetal rats of fetal growth retardation (FGR) and its relation with expression of caspase-3 on the placenta of maternal rat. METHODS: Model of FGR was constructed according to the method of passive smoking. The pregnant rats were divided into control group (n = 10), therapy group (n = 18) and FGR group (n = 10). The therapy group rats were given different doses of magnesium sulfate by subcutaneous injection: low dose group (300 mg/kg, n = 10), high dose group (600 mg/kg, n = 8). Serum concentration of magnesium sulfate was monitored. The expression of caspase-3 was measured by immunohistochemistry method and RT-PCR. RESULTS: Both of the concentration of magnesium sulfate in high and low dose groups (0.72 +/- 0.13), (0.61 +/- 0.03) mmol/L were higher than the FGR group (0.55 +/- 0.03) mmol/L (P < 0.01); the weight of placenta and fetal rat in high dose group [(0.80 +/- 0.16) and (3.58 +/- 0.10) g] were more than those of FGR group [(0.63 +/- 0.05) and (2.95 +/- 0.46) g] (P < 0.05, P < 0.01); the expression of mRNA and protein of caspase-3 in high dose group [(0.361 +/- 0.030), (183.0 +/- 3.3)] was lower than the FGR group [(0.626 +/- 0.036), (199.5 +/- 4.7)] (P < 0.05); the expression of mRNA in low dose group (0.525 +/- 0.029) was higher than the high dose group (P < 0.05); serum concentration of magnesium sulfate of maternal rat was correlated with the weight of fetal rat (r = 0.899, P = 0.038) and the expression of mRNA and protein of caspase-3 in placenta (r = -0.747, P = 0.033; r = -0.915, P = 0.001). CONCLUSION: It is suggested that magnesium sulfate increases the weight of fetal rat probably by depressing the expression of caspase-3 of placenta, which improves the placental function.