[Changes of matrix metalloproteinase-9 and effect of diazepam on its expression in uterine lower segment during delivery].
OBJECTIVE
To investigate the role of matrix metalloproteinases (MMPs) in onset of labor, and the mechanism of diazepam in promoting cervical ripening.


METHODS
Concentrations of MMP-9 in lower segment of uterus from the group of cesarean section with (56 cases) and without (16 cases) uterine contraction were measured by enzyme linked immunosorbent assay (ELISA) method. Human cervical mechanocytes were cultured respectively with different concentrations of diazepam (0, 0.1, 10, 100 micromol/L). Semi-quantitative RT-PCR was used to study the expression of MMP-9 mRNA, and MMP-9 contents in culture supernatant were measured by ELISA methods.


RESULTS
The concentration of MMP-9 in uterine lower segment tissue in the group of cesarean section with uterine contraction, (3.1 +/- 2.6) ng/mg, was significantly higher than that in the group of cesarean section without uterine contraction, (0.8 +/- 0.4) ng/mg (P < 0.05). In the 1st-stage-labour group from the 44 cases of cesarean section with uterine contraction, MMP-9, (2.2 +/- 2.0) ng/mg, tended to increase with the dilatation of cervix. MMP-9 in the 12 cases of 2nd-stage-labour group was (6.1 +/- 2.5) ng/mg, which was significantly higher than that in the 1st-stage-labour group (P < 0.05). The relative expressions of MMP-9 mRNA in the cells of the blank control group and those with diazepam at final concentrations of 0.1, 10 micromol/L were all time dependent, in another word, the expressions gradually increased over time. There was a remarkable difference between the two groups and blank control group (P < 0.05). In the blank control group and group with diazepam at final concentration of 0.1 micromol/L, the MMP-9 contents in supernatant showed a time dependent increase, with a significant difference between the two groups (P < 0.05).


CONCLUSIONS
MMPs are key mediator in the onset of labor, maturation and dilatation of uterine cervix. Our studies suggest that human cervical mechanocytes play a role in synthesizing and secreting MMP-9 naturally; and diazepam might promote those activities of mechanocytes, thus in part accelerating the degradation of collagen fibers and cervical ripening.
Jin
Zhen
Z
Department of Obstetrics and Gynecology, Second Affiliated Hospital, China Medical University, Shenyang 110004, China.
Wang
Wei
W
Ma
Yan
Y
Guan
Zhe
Z
Wu
Bin
B
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000201:enzymology; D002585:Cesarean Section; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007743:Labor, Obstetric / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D000759:Adjuvants, Anesthesia; D020780:Matrix Metalloproteinase 9; D003975:Diazepam