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
10.3760/cma.j.issn.1007-9408.2012.05.006
- VernacularTitle:脂氧素受体激动剂5(S),6(R),7-三羟基庚酸甲酯对地塞米松所致小鼠胎儿生长受限的保护作用及可能机制
- Author:
Jinxia CHEN
;
Yinping HUANG
;
Zhangye XU
;
Biao TANG
;
Jianming GONG
;
Min WANG
- Publication Type:Journal Article
- Keywords:
Fetal growth retardation;
Heptanoic acids;
11-beta-Hydroxysteroid dehydrogenase type 2;
Dexamethasone;
Mice
- From:
Chinese Journal of Perinatal Medicine
2012;15(5):282-287
- CountryChina
- Language:Chinese
-
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 8:00 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.
