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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 prevention and treatment of preeclamptic mouse model and to explore the minimum dose and optimal time of aspirin for preventing preeclampsia. Methods Phosphatidylserine / phosphatidylcholine micelles were used to establish the model of preeclampsia mice by continuous tail vein injection on the 5th to 16th day of gestation. The normal mice were treated with normal saline as the control, The mice in M0, M1, M2, and M3 groups were treated with saline (M0, m0) on the 10th to 16th days (m0, m1, m2 and m3) (M1, m1 group), 0.27 mg / d (M2, m2 group) and 0.53 mg / d (M3, m3 group). The blood pressure, 24 h urinary protein and placenta weight, birth weight, litter size and stillbirth rate were measured. The placental fibrin deposition area was observed by immunohistochemistry. Results ① The area of blood pressure, urinary protein and placental fibrin deposition in mice in M0 and m0 group were significantly higher than those in normal control group (P <0.05). ② The differences of M0 and M0 in observation group were statistically significant (P <0.05) ; There was no significant difference between M1 and M0 groups (P> 0.05); there was no significant difference between M2 and M3 groups (P> 0.05); ③m0, m1, m2 and m3 groups had no significant difference P> 0.05). Conclusion Low dose aspirin 0.27 mg / d (equivalent to human 100 mg / d) on the 5th day of gestation can effectively improve the placental blood circulation, reduce the formation of micro-thrombi in the placenta and improve the prognosis of female rats and fetuses.