地西泮对妊娠期大鼠宫颈组织MMP-9/TIMP-1表达的影响

The Expression of MMP-9/TIMP-1 in Cervix Tissue of Pregnancy Rat

目的探讨地西泮促进妊娠期大鼠宫颈成熟和扩张的作用及其可能机制。方法建立妊娠大鼠动物模型,随机分为4组,实验3组,分别为大鼠妊娠11d(中期)及18d(晚期)给予地西低剂量(0.5mg·kg-1·d-1)、中剂量(1.0mg·kg-1·d-1)、高剂量(2.0mg·kg-1·d-1),给予0.9%生理盐水(2.0mg·kg-1·d-1)作为对照组。用蛋白印迹法测定其基质金属蛋白酶9(MMP-9)/金属蛋白酶组织抑制因子1(TIMP-1)的蛋白表达。结果随着妊娠进展宫颈组织MMP-9/TIMP-1表达增加,妊娠晚期较中期MMP-9/TIMP-1表达增加明显(P<0.05);妊娠中期不同剂量地西泮组宫颈组织MMP-9/TIMP-1表达与对照组相比无显著性差异;妊娠晚期地西泮中、高剂量组宫颈组织MMP-9/TIMP-1表达均较对照组变化显著(P<0.01),而总MMP-9蛋白浓度的表达无显著差异(P>0.05)。结论一定剂量的地西泮具有增加宫颈组织MMPs活性的作用,从而促进妊娠晚期宫颈成熟和扩张。

Objective To explore the effects of diazepam on MMP-9/TIMP-1 of cervix tissue in pregnancy rat. Methods 40 rats were divided into four groups randomly after establishing rats pregnancy model. Then they were given diazepam once a day for 2 days,in the dosage of 0.5 mg·kg^-1·d^-1 （low dosage）, 1.0 mg·kg^-1·d^-1 （intermediate dosage）,2.0 mg·kg^-1·d^-1 （high dosage） in 11th day（meddle stage）and 18th day （late stage）. The same volume of NS was given as a control group. We determined MMP-9/TIMP-1＇s protein expression with the Western blotting. Results Along with the advance of gestation,expression of MMP-9/TIMP-1 increased. This increase of MMP-9/ TIMP-1 is more significant in late stage than that in middle stage （P 〈 0.05）. Compared with control group,there were no significant change in MMP-9/TIMP-1 in intermediate stage at different dosage of diazepam,but the changes were significant in late pregnancy state at the middle dosage and high dosage （P 〈 0.01 ）. There was no significant change in total concentration of MMP-9 protein. Conclusion Administration of diazepam can decrease cervix tensity and induce the activation of MMP-9, thus promote cervix ripening and dilatation.