基质金属蛋白酶抑制剂引起大鼠流产的实验模型

Rat Model of Abortion Induced by Matrix Metalloproteinases Inhibitor 1,10-phenanthroline

目的应用基质金属蛋白酶抑制剂1,10菲罗啉作用于妊娠大鼠造成流产的模型,以验证基质金属蛋白酶在正常妊娠中的作用。方法妊娠Wistar大鼠随机分为4组,A组腹腔注射生理盐水作为对照组,B、C、D组分别于妊娠早期、妊娠中期及妊娠全程腹腔注射基质金属蛋白酶抑制剂1,10-菲罗啉,各组例数均为10例。于受孕21.5d剖宫产,统计胎仔数、胚胎丢失数及流产率,并分别称取胎仔体重和胎盘重量,RTPCR检测胎盘基质金属蛋白酶-9(MMP-9)mRNA的表达。结果基质金属蛋白酶抑制剂1,10-菲罗啉能导致大鼠胚胎丢失,自B组至D组流产率逐渐增高,并且C组和D组胎仔体重明显低于对照组,RT-PCR亦证实孕鼠腹腔注射1,10-菲罗啉后其胎盘MMP9mRNA的表达显著下降,其下降程度与1,10-菲罗啉的干预时限成正比。结论基质金属蛋白酶抑制剂在妊娠期抑制MMPs的表达,使MMPs的分泌不足,导致流产或胎鼠宫内生长迟缓,提示MMPs在胎盘滋养细胞浸润和妊娠的维持中具有重要作用。

Objective To investigate abortion induced by 1,10-phenanthroline （a matrix metaUoproteinase inhibitor） in rats, and to explore the detrimental influence of metalloproteinases on pregnancy. Methods Pregnant Wistar rats were randomly divided into 4 groups, 10 rats in each group. Group A （control group） was injected intraperitoneally with saline 0.25 ml every other day. Group B,C and D were treated by intraperitoneal injection of 1,10-phenanthroline in a dose of 25 mg/kg every other day,on gestational d0.5～ d7,d0.5 ～ d14 and d0.5～d21 ,respectively. All rats were terminated on d21.5. Number of offspring, number of embryo loss, weight of offspring and weight of placenta were counted or measured. Expression of MMP-9mRNA in placenta was examined by reverse transcription-polymerase chain reaction （RT-PCR）. Results The embryo loss rate in group B, C and D was significant higher than that in group A （P 〈 0.001 ）. The embryo loss rate in group B, C and D was significantly lower than that of group （ P 〈 0.005）. Expression of MMP-9mRNA in placenta was significantly decreased in group B, C and D compared with that of group A （ P 〈 0. 001 ）. Conclusion A rat model of abortion induced by matrix metalloproteinases inhibitor 1,10-phenanthroline is successfully established. Embryo loss and abortion in pregnant rats can be induced by this procedure. MMPs play an important role in the invasion of trophoblasts and the maintenance of placenta during pregnancy.