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.
ABSTRACT
A aldosterona é o mais importante mineralocorticóide circulante. É secretada pela zona glomerulosa da glândula adrenal e atua em orgãos-alvo tais como os rins, cólon, glândulas salivares e sudoríparas por meio de mecanismos genômicos, a fim de manter o equilíbrio hidroeletrolítico do organismo. Mais recentemente vêm surgindo novas descobertas sobre as ações da aldosterona, as quais não se mostram restritas aos alvos clássicos de sua ação. Orgãos como coração, vasos e muitos locais do sistema nervoso central (SNC), são apontados como novos alvos da ação da aldosterona, mostrando efeitos fisiológicos bem como fisiopatológicos, que na maioria das vezes relacionam-se a mecanismos não-genômicos. Os principais efeitos da aldosterona nesses novos alvos incluem: estimulação do apetite ao sódio (Na+), aumento da pressão arterial basal, prejuízo do barorreflexo arterial e produção de hipertrofia e fibrose no tecido cardíaco. Esses novos achados enaltecem o papel da aldosterona como o hormônio-chave no controle cardiovascular. No entanto, os mecanismos envolvidos na produção desses efeitos permanecem desconhecidos e novos estudos são necessários para o seu completo entendimento. O principal objetivo desta revisão será sumariar diversos estudos que indicam o envolvimento da aldosterona nos mecanismos de controle cardiovascular e do equilíbrio hidroeletrolítico do organismo.
Aldosterone is the most important circulating mineralocorticoid. It is secreted by the zona glomerulosa of the adrenal gland and acts on target tissues such as the kidney, colon, salivary and sweat glands by genomic mechanisms to maintain water and salt balance. More recently it has become clear that aldosterone also acts on tissues not directly involved in regulation of water and salt balance. Tissues like the heart, the vascular wall, and the central nervous system (CNS) are targets for aldosterone, which exerts its physiologic and pathophysiologic effects through both genomic and non-genomic mechanisms. The effects of aldosterone on these non-classical targets include sodium appetite, hypertension, impaired baroreceptor reflex, and cardiac hypertrophy and fibrosis. These findings reinforce the importance of aldosterone as a key cardiovascular hormone. The mechanisms that mediate these non-classical effects remain a subject of intense study. This paper reviews the involvement of aldosterone in neural mechanisms that control the cardiovascular system and water and salt balance.