中华围产医学杂志
中華圍產醫學雜誌
중화위산의학잡지
CHINESE JOURNAL OF PERINATAL MEDICINE
2012年
5期
282-287
,共6页
陈金霞%黄引平%许张晔%汤彪%龚建明%汪敏
陳金霞%黃引平%許張曄%湯彪%龔建明%汪敏
진금하%황인평%허장엽%탕표%공건명%왕민
胎儿生长迟缓%庚酸类%11-β-羟甾脱氢酶2型%地塞米松%小鼠
胎兒生長遲緩%庚痠類%11-β-羥甾脫氫酶2型%地塞米鬆%小鼠
태인생장지완%경산류%11-β-간치탈경매2형%지새미송%소서
Fetal growth retardation%Heptanoic acids%11-beta-Hydroxysteroid dehydrogenase type 2%Dexamethasone%Mice
目的 探讨5(S),6(R),7-三羟基庚酸甲酯[5(S),6(R),7-trihydroxyheptanoic acid methyl ester,BML-111]对地塞米松所致小鼠胎儿生长受限的影响及可能机制. 方法 60只清洁级ICR雌性小鼠受孕后随机分为对照组、地塞米松组和BML-111组.地塞米松组孕鼠妊娠第9天开始皮下注射地塞米松(5 mg/kg),2h后皮下注射生理盐水(1 mg/kg) ;BML-111组孕鼠妊娠第9天开始皮下注射地塞米松,2h后腹腔注射BML-111(1 mg/kg);对照组孕鼠相应时间皮下注射生理盐水(1 mg/kg).均为每天1次,连续6d.妊娠第18天眼球取血后处死孕鼠,取胎盘和子宫组织,免疫组织化学方法检测胎盘组织11β-羟基类固醇脱氢酶2(11β-hydroxysteroid dehydrogenase 2,11β-HSD2)蛋白表达；逆转录聚合酶链反应技术检测胎盘组织11β-HSD2、白细胞介素- 1β(in terleukin-1β,IL-1β)及子宫组织脂氧素A4受体——甲酸基肽受体3(formyl peptide receptor 3,FPR3) mRNA的表达；酶联免疫吸附试验检测孕鼠血清脂氧素A4水平.组间差异比较采用单因素方差分析及两两检验.结果 地塞米松组胎鼠平均体重为(0.823±0.054)g,低于对照组[(1.103±0.218)g]及BML-111组[(0.992±0.207)g],差异均有统计学意义(t分别为-4.108和-2.890,P均＜0.05).免疫组织化学方法检测显示,11β-HSD2表达于绒毛部位合体滋养层细胞胞质内,地塞米松组11β-HSD2蛋白表达强度较对照组及BML-111组低(0.030±0.019与0.058±0.015和0.049±0.025),差异均有统计学意义(t分别为-3.107和-2.211,P均＜0.05).地塞米松组11β-HSD2 mRNA也较对照组及BML-111组低,分别为0.457±0.062、0.943±0.057和0.698±0.071,差异有统计学意义(t分别为-9.418和-4.617,P均＜0.05).地塞米松组IL-1β mRNA(0.543±0.103)介于对照组(0.710±0.085)及BML-111组(0.229±0.031)之间,差异有统计学意义(t分别为-3.736和7.025,P均＜0.05).地塞米松组FPR3 mRNA(0.323±0.019)较对照组(0.857±0.057)及BML-111组(0.499±0.050)低,差异有统计学意义(t分别为-14.630和-4.822,P均＜0.05).地塞米松组孕鼠血清脂氧素A4浓度[(64.463±22.144)pg/ml]低于对照组[(101.610±24.916)pg/ml],差异有统计学意义(t=3.152,P＜0.05). 结论 孕鼠过早过多接触地塞米松可导致胎儿生长受限.BML-111可能通过调节11β-HSD2的表达,从而改善糖皮质激素在孕鼠体内的代谢而对地塞米松所致胎儿生长受限起保护作用.
目的 探討5(S),6(R),7-三羥基庚痠甲酯[5(S),6(R),7-trihydroxyheptanoic acid methyl ester,BML-111]對地塞米鬆所緻小鼠胎兒生長受限的影響及可能機製. 方法 60隻清潔級ICR雌性小鼠受孕後隨機分為對照組、地塞米鬆組和BML-111組.地塞米鬆組孕鼠妊娠第9天開始皮下註射地塞米鬆(5 mg/kg),2h後皮下註射生理鹽水(1 mg/kg) ;BML-111組孕鼠妊娠第9天開始皮下註射地塞米鬆,2h後腹腔註射BML-111(1 mg/kg);對照組孕鼠相應時間皮下註射生理鹽水(1 mg/kg).均為每天1次,連續6d.妊娠第18天眼毬取血後處死孕鼠,取胎盤和子宮組織,免疫組織化學方法檢測胎盤組織11β-羥基類固醇脫氫酶2(11β-hydroxysteroid dehydrogenase 2,11β-HSD2)蛋白錶達；逆轉錄聚閤酶鏈反應技術檢測胎盤組織11β-HSD2、白細胞介素- 1β(in terleukin-1β,IL-1β)及子宮組織脂氧素A4受體——甲痠基肽受體3(formyl peptide receptor 3,FPR3) mRNA的錶達；酶聯免疫吸附試驗檢測孕鼠血清脂氧素A4水平.組間差異比較採用單因素方差分析及兩兩檢驗.結果 地塞米鬆組胎鼠平均體重為(0.823±0.054)g,低于對照組[(1.103±0.218)g]及BML-111組[(0.992±0.207)g],差異均有統計學意義(t分彆為-4.108和-2.890,P均＜0.05).免疫組織化學方法檢測顯示,11β-HSD2錶達于絨毛部位閤體滋養層細胞胞質內,地塞米鬆組11β-HSD2蛋白錶達彊度較對照組及BML-111組低(0.030±0.019與0.058±0.015和0.049±0.025),差異均有統計學意義(t分彆為-3.107和-2.211,P均＜0.05).地塞米鬆組11β-HSD2 mRNA也較對照組及BML-111組低,分彆為0.457±0.062、0.943±0.057和0.698±0.071,差異有統計學意義(t分彆為-9.418和-4.617,P均＜0.05).地塞米鬆組IL-1β mRNA(0.543±0.103)介于對照組(0.710±0.085)及BML-111組(0.229±0.031)之間,差異有統計學意義(t分彆為-3.736和7.025,P均＜0.05).地塞米鬆組FPR3 mRNA(0.323±0.019)較對照組(0.857±0.057)及BML-111組(0.499±0.050)低,差異有統計學意義(t分彆為-14.630和-4.822,P均＜0.05).地塞米鬆組孕鼠血清脂氧素A4濃度[(64.463±22.144)pg/ml]低于對照組[(101.610±24.916)pg/ml],差異有統計學意義(t=3.152,P＜0.05). 結論 孕鼠過早過多接觸地塞米鬆可導緻胎兒生長受限.BML-111可能通過調節11β-HSD2的錶達,從而改善糖皮質激素在孕鼠體內的代謝而對地塞米鬆所緻胎兒生長受限起保護作用.
목적 탐토5(S),6(R),7-삼간기경산갑지[5(S),6(R),7-trihydroxyheptanoic acid methyl ester,BML-111]대지새미송소치소서태인생장수한적영향급가능궤제. 방법 60지청길급ICR자성소서수잉후수궤분위대조조、지새미송조화BML-111조.지새미송조잉서임신제9천개시피하주사지새미송(5 mg/kg),2h후피하주사생리염수(1 mg/kg) ;BML-111조잉서임신제9천개시피하주사지새미송,2h후복강주사BML-111(1 mg/kg);대조조잉서상응시간피하주사생리염수(1 mg/kg).균위매천1차,련속6d.임신제18천안구취혈후처사잉서,취태반화자궁조직,면역조직화학방법검측태반조직11β-간기류고순탈경매2(11β-hydroxysteroid dehydrogenase 2,11β-HSD2)단백표체；역전록취합매련반응기술검측태반조직11β-HSD2、백세포개소- 1β(in terleukin-1β,IL-1β)급자궁조직지양소A4수체——갑산기태수체3(formyl peptide receptor 3,FPR3) mRNA적표체；매련면역흡부시험검측잉서혈청지양소A4수평.조간차이비교채용단인소방차분석급량량검험.결과 지새미송조태서평균체중위(0.823±0.054)g,저우대조조[(1.103±0.218)g]급BML-111조[(0.992±0.207)g],차이균유통계학의의(t분별위-4.108화-2.890,P균＜0.05).면역조직화학방법검측현시,11β-HSD2표체우융모부위합체자양층세포포질내,지새미송조11β-HSD2단백표체강도교대조조급BML-111조저(0.030±0.019여0.058±0.015화0.049±0.025),차이균유통계학의의(t분별위-3.107화-2.211,P균＜0.05).지새미송조11β-HSD2 mRNA야교대조조급BML-111조저,분별위0.457±0.062、0.943±0.057화0.698±0.071,차이유통계학의의(t분별위-9.418화-4.617,P균＜0.05).지새미송조IL-1β mRNA(0.543±0.103)개우대조조(0.710±0.085)급BML-111조(0.229±0.031)지간,차이유통계학의의(t분별위-3.736화7.025,P균＜0.05).지새미송조FPR3 mRNA(0.323±0.019)교대조조(0.857±0.057)급BML-111조(0.499±0.050)저,차이유통계학의의(t분별위-14.630화-4.822,P균＜0.05).지새미송조잉서혈청지양소A4농도[(64.463±22.144)pg/ml]저우대조조[(101.610±24.916)pg/ml],차이유통계학의의(t=3.152,P＜0.05). 결론 잉서과조과다접촉지새미송가도치태인생장수한.BML-111가능통과조절11β-HSD2적표체,종이개선당피질격소재잉서체내적대사이대지새미송소치태인생장수한기보호작용.
Objective To 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. Methods The 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. Results The 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]. Conclusions BML-111 regulate the expression of 11β-HSD2 and then protect against FGR resulted from too much prenatal application of dexamethasone.
