阿司匹林对小鼠子痫前期防治效果的研究

Effect of aspirin on the pre-eclamptic mouse model

目的研究小剂量阿司匹林防治子痫前期小鼠模型的效果,探讨阿司匹林用于预防子痫前期的最低剂量和最佳时间。方法应用磷脂酰丝氨酸/磷脂酰胆碱微团,于妊娠第5～16天连续尾静脉注射法诱导建立子痫前期小鼠模型,并以应用生理盐水的正常小鼠作对照,分别于妊娠第5～16天(M0、M1、M2、M3组小鼠)、第10～16天(m0、m1、m2、m3组小鼠):给予生理盐水(M0、m0组),阿司匹林0.13 mg/d(M1、m1组)、0.27 mg/d(M2、m2组)和0.53 mg/d(M3、m3组)。测定小鼠的血压、24 h尿蛋白及胎盘体质量、胎仔体质量、胎仔数和死胎率,应用免疫组化方法观察胎盘纤维蛋白沉积面积。结果①M0、m0组小鼠血压、尿蛋白、胎盘纤维蛋白的沉积面积较各自正常对照组明显增加(P<0.05);②M2、M3组各观察指标较M0差异有统计学意义(P<0.05);M1组与M0组比较差异无统计学意义(P>0.05);M2、M3组比较差异无统计学意义(P>0.05);③m0、m1、m2、m3组间比较差异无统计学意义(P>0.05)。结论自妊娠第5天应用小剂量阿司匹林0.27 mg/d(相当于人100 mg/d)能有效改善胎盘的血液循环,减少胎盘微血栓的形成,有效改善母鼠及胎仔的预后。

Objective To study the effect of low-dose aspirin on the pre-eclamptic mouse model,and explore the lowest dose and best time for using aspirin to prevent preeclampsia.Methods To establish the pre-eclamptic mouse model,mice were injected with phosphatidylserine/phosphatidylcholine microvesicles in tail veins from days 5 to 16 of pregnancy.From days 5 to 16（groups M0,M1,M2 and M3）or days 10 to 16（groups m0,m1,m2 and m3）,mice were given saline（M0 and m0）,or aspirin at 0.13mg/d（M1 and m1）,0.27mg/d（M2 and m2） and 0.53mg/d（M3 and m3）.Systolic blood pressure（SBP） and 24h proteinuria were measured.The weights of the placenta and fetus,and the number of fetuses were evaluated.The placental fibrin deposition area was detected using immunohistochemistry.Results ①Compared with the controls,the mice given saline（M0 or m0） showed a significant elevation in SBP,a decrease in proteinuria and a more diffuse fibrin deposition area（P0.05）.②In all above markers,M2 and M3 had significant differences compared with M0（P0.05）,while there was no significant difference between M2 and M3（P0.05）.③There was no significant difference among the mice given aspirin from days 10 to 16 of pregnancy（m1,m2 and m3）（P0.05）.Conclusion Using aspirin at 0.27mg/d（about 100mg/d for human） from day 5 of pregnancy can improve placental blood circulation in the pre-eclamptic mouse model,decrease the formation of microthrombus,and benefit the mother and fetus.