The Study Of The Effect Of N-acetylcysteine On LPS/NF-κB Signal Transduction And Progesterone Receptor Subtype In Infection Associated Preterm Labor

[Abstract] Objective To study the treatment effect of NAC on the animal model of infection associated preterm labor. Methods 1.Primary culture uterine smooth muscle cells from term pregnant without labor were treated with LPS (10 ug/ml),or LPS+NAC(10umol/l) and intracellular ROS and calcium level were analyzed.After-8h incubation,the cells were collected, NF-κB activity was assessed by Western blotting and IL-8 mRNA was determined by RT-PCR.At the same time,The incubation medium was collected and assayed for IL-8 concentration.2, NAC was administered orally to C 57BL/6 m ice i njected i ntraperitoneally w ith e ither 1 Oug LPS o r s aline solution on day 16 or 15 of gestation.The latency period(time from injection to delivery of the first pup) and fetal viability were recorded.To discriminate between an effect of prematurity from an effect of inflammation,including NF-kB activity and IL-8 mRNA in uterine and maternal and fetal hepatic GSH-PX and MDA,SOD in serum,mice were killed at 4,8,12,24h after injection. 3,The uterine tissues of the threated preterm labor, preterm in labor and term pregnant without labor and in labor were collected from section of lower uterine, and PR-A, PR-B and COX-2mRNA were assayed by SYBR Green RT-PCR and the protein level of those were done by immunohistochemistry. Results After the uterine smooth muscle cells were stimulated with LPS,LPS elicited a time-dependent oxidative burst with H2DCFDA dye oxidation.The intracelluar Ca²⁺ was found to peak after60min with treated with LPS and inhibited by NAC.2, NAC doubled the latency interval of LPS-treated animals to 35.4h,NAC orally in advanced prolonged the latency 44.8h,livebirth rate was raised to 69%,materal and fetal hepatic GSH level was improved and NF-kB were activated after 4 h. The concentration of IL-8 and MDA was raised at 8h.NAC can inhibited the peak. 3 ^ The PR-A/PR-B of preterm in labor were higher than the threaten preterm labor were positive correlation with C0X-2mRNA.NAC+LPS interfered with pregenant mice can inhibit PR-A/PR-B of uterine tissues by LPS (FKO. 05) . Conclusions NAC has a positive treatment on LPS-induced preterm labor in mice,the effect of prophylaxis was more than that of treatment.lt can inhibite the activation of NF-KB/IL-8.reduce ROS and take a protective effect on fetus.2 > NAC can inhibite intracellular Ca2+ and activation of NF-kB/IL-8 signal transduction. 3 ^ The labor onset was associated with PR-A/PR-B,and inhibited by NAC in animal model.