黄芪注射液对子痫前期大鼠胎盘NF-κB、MMP-9、转录因子的影响

Impact of Astragalus injection on NF-κB, MMP-9 and transcription factors in placenta of rats with preeclampsia

目的观察黄芪注射液对子痫前期大鼠尿蛋白、胎盘核转录因子(NF-κB)、基质金属蛋白酶9(MMP-9)及相关转录因子表达的影响。方法随机将妊娠大鼠分为模型组、黄芪组和对照组,10只/组。在妊娠第13~15 d时,模型组和黄芪组皮下注射N-硝基-L-精氨酸甲酯(L-NAME)50 mg/(kg·d),建立子痫前期大鼠模型;对照组注射等量生理盐水。自妊娠第16 d起,黄芪组腹腔注射黄芪注射液,模型组和对照组注射同体积5%葡萄糖注射液,给药持续5 d。在妊娠第15和20 d时,检测3组动脉压和尿蛋白水平;在妊娠第20 d时,检测3组胎盘组织NF-κB、MMP-9、核转录因子5(NFAT-5)、胎盘生长因子(PLGF)、可溶性血管内皮生长因子受体1(sFlt-1)mRNA表达水平。结果在妊娠第15 d,模型组与黄芪组动脉压和尿蛋白水平高于对照组(P<0.05);在妊娠第20 d,黄芪组动脉压和尿蛋白水平低于模型组(P<0.05),NF-κB、sFlt-1mRNA表达水平为:对照组<黄芪组<模型组,MMP-9 mRNA表达水平为:对照组>黄芪组>模型组,组间差异均显著(P<0.05);模型组NFAT-5 mRNA表达水平明显最高,而PLGF mRNA表达水平最低(P<0.05)。结论黄芪注射液能抑制子痫前期大鼠胎盘组织中的sFlt-1 mRNA、NFAT-5、NF-κB表达,增强PLGF mRNA、MMP-9表达,这可能是其治疗子痫前期的作用机理之一。

Objective To observe the impact of Astragalus injection on the expression of urine protein,nuclear transcription factor(NF-κB)in placenta,matrix metal protease-9(MMP-9)and other transcription factors in rats with preeclampsia.Methods The pregnant rats were randomly divided into a model group,an Astragalus group and a control group,10 rats per group.On Day 13 to 15 of pregnancy,the model group and Astragalus group were subcutaneously injected with N’-Nitro-L-arginine-methyl ester(L-NAME)at a dose of 50 mg/(kg·d),so as to construct the preeclampsia models;the control group was injected with the normal saline with the same amount.Since Day 16 of pregnancy,the Astragalus group was intraperitoneally injected with the Astragalus injection,the model group and control group with 5%glucose injection with the same volume for five days.On Day 15 and 20 of pregnancy,the arterial pressure and urine protein levels in these three groups were detected;on Day 20 of pregnancy,the expression levels of NF-κB in placenta tissues,MMP-9,nuclear factor of activated T cells 5(NFAT-5),placental growth factor(PLGF),and soluble vascular endothelial growth factor receptor 1(sFlt-1)mRNA were detected for all three groups.Results On Day 15 of pregnancy,the model group and Astragalus group were higher than the control group in arterial pressure and urine protein levels(P<0.05);on Day 20 of pregnancy,the Astragalus group was lower than the model group in arterial pressure and urine protein levels(P<0.05);the expression rank of NF-κB and sFlt-1 mRNA was control group<Astragalus group<model group;the rank of MMP-9 mRNA expression was control group>Astragalus group>model group,with significant differences among them(P<0.05);the model grouphad the highest expression of NFAT-5 mRNA,and the lowest expression of PLGF mRNA(P<0.05).Conclusion The Astragalus injection can inhibit the expression of sFlt-1 mRNA,NFAT-5 and NF-κB in the placenta tissues of rats with preeclampsia,and reinforce the expression of PLGF mRNA and MMP-9,which may be the working mechanism to cure preeclampsia.