Effect and mechanism of 5 (S), 6 (R), 7-trihydroxyheptanoic acid methyl ester on pregnant mice complicated with fetal growth restriction induced by antenatal dexamethasone / 中华围产医学杂志

ABSTRACT

ObjectiveTo investigate the effects of 5(S),6(R),7-trihydroxyheptanoic acid methyl ester (BML-111) on pregnant mice with fetal growth restriction(FGR) induced by antenatal dexamethasone and its probable mechanism. MethodsThe mice were mated overnight,with day 1 of pregnancy designated as the day on which spermatozoa were presented in a vaginal smear.The pregnant mice were then randomly divided into control group,dexamethasone group and BML-111 group.From 9 to 14 days of pregnancy,pregnant ICR mice of control,dexamethasone and BML-111 group were treated separately with saline,dexamethasone(5 mg/kg) and dexamethasone at 800 am,and two hours later they were treated separately again with 1 mg/kg saline,saline and BML-111.On the day 18 of gestation,they were sacrificed after blood were collected from their eyeballs.The serum lipoxin A4 was measured with enzyme-linked immunosorbent assay. Fetuses were delivered by cesarean section; the placenta and uterus were immediately removed and frozen.Gene expressions of 11β-hydroxysteroid dehydrogenase 2 ( 11β-HSD2 ),interleukin-1β (IL-1β) in placenta and lipoxin A4 receptor-formyl peptide receptor 3 (FPR3)in uterine were detected by reverse transcriptionpolymerase chain reaction and compared with analysis of variance.The 11β-HSD2 protein in mice placenta was detected by immunohistochemistry. ResultsThe mean fetal weight of dexamethasone group was (0.823±0.054) g,lower than that of the control group and BML-111 group [(1.103±0.218) g and (0.992 ± 0.207) g] (t =- 4.108 and - 2.890,P ＜ 0.05 respectively).Protein expression of 11β-HSD2 in dexamethasone group (0.030±0.019) was weaker than that in control group (0.058±0.015,t=-3.107,P＜0.05) or in BML-111 group (0.049±0.026,t=-2.211,P＜0.05).The expression of 11β-HSD2 mRNA in dexamethasone group (0.457±0.062) was lower than that in control group (0.943±0.057,t=-9.418,P＜0.05) or in BML-111 group (0.698±0.071,t=-4.617,P＜0.05).Expression of IL-1β mRNA in dexamethasone group (0.543±0.103)was less than that in control group (0.710± 0.085,t=-3.736,P＜0.05) but more than that in BML-111 group (0.229 ±0.031,t=7.025,P＜0.05). The expression of FPR3 mRNA in dexamethasone group (0.323 ± 0.019) was less than that in control group (0.857 ± 0.057,t =-14.630,P＜0.05) or in BML-111 group (0.499 ±0.050,t=-4.822,P＜0.05).The serum concentration of lipoxin A4 in dexamethasone group was lower than that in control group [(64.463±22.144) pg/ml vs (101.610±24.916) pg/ml,t=3.152,P＜0.05].ConclusionsBML-111 regulate the expression of 11β-HSD2 and then protect against FGR resulted from too much prenatal application of dexamethasone.