摘要
目的使用高分辨超声血流介导的血管舒张功能(flow-mediated dilation,FMD)评价高盐饮食对子痫前期大鼠内皮功能的影响,为指导子痫前期孕妇合理膳食提供科学依据。方法将18只Sprague Dawley(SD)雌性大鼠随机分为高盐饮食(high-salt diet,HS)组和正常盐饮食(normal-salt diet,NS)组,每组各9只,分别给予高盐饮食和正常盐饮食。8周后受孕,自妊娠第9天起每日在大鼠颈背部皮下注射左旋硝基精氨酸甲酯(NG-nitro-L-arginine methyl ester,L-NAME),直至妊娠第19天建立子痫前期大鼠模型。测量大鼠基线、第4周、第8周、妊娠第8天及妊娠第19天的血压和24 h尿蛋白水平。在妊娠第19天使用高分辨率小动物超声实时分子影像系统检测大鼠股动脉FMD。结果两组大鼠的终末体重无显著差异(t=-1.65,P=0.12);HS组大鼠的收缩压、平均动脉压及24 h尿蛋白水平均显著高于NS组(F_(收缩压)=96.86,P <0.01;F_(平均动脉压)=47.75,P <0.01;F_(24h尿蛋白)=56.54,P <0.01)。两组大鼠的FMD均于300 s时达到峰值,HS组大鼠股动脉FMD峰值显著低于NS组(F=175.35,P <0.01)。结论高盐饮食大鼠股动脉血管舒张功能降低,提示高盐饮食可能对子痫前期内皮功能损害更大。
Objective To evaluate the effect of high-salt diet on endothelial function in preeclampsia rats by flow-mediated dilation(FMD) and provide a scientific basis for guiding reasonable dietary salt in pregnancy women with pre-eclampsia. Method18 Sprague-Dawley(SD) female rats were randomly divided into high-salt diet(HS) group(n = 9) and normal-salt diet(NS) group(n = 9), fed high-salt diet and normal-salt diet respectively. After 8 weeks of conception, NG-nitro-L-arginine methyl ester(L-NAME) was injected subcutaneously into the neck of the rats daily from the gestational day(GD) 9 until the GD 19 to build a pre-eclampsia rat model. Blood pressure and 24-hour urine protein levels were measured at baseline, 4~(th) week, 8~(th) week, GD 8, and GD 19. High-resolution small animal ultrasound real-time molecular imaging system was used on the GD 19 to test femoral artery FMD. Result There was no significant difference in the final body mass between the two groups of rats(t =-1.65, P = 0.12); systolic blood pressure(SBP), mean arterial pressure(MAP) and 24-hour urine protein levels in HS group were higher than those in NS group(F_(SBP)= 96.86, P < 0.01; F_(MAP)= 47.75, P < 0.01; F_(24-hour urine protein)= 56.54, P < 0.01). The FMD of all experimental rats reached the highest point at 300 s. The peak value of FMD in HS group was lower than NS group(F = 175.35, P < 0.01). Conclusion High-salt diet reduces diastolic function of femoral artery in rats indicate that high salt diet may have greater damage to endothelial function in pre-eclampsia.
引文
[1]Huang P,Chen S,Wang Y,et al.Down-regulated CBS/H2Spath w ay is involved in high-salt-induced hypertension in Dahl rats[J].Nitric Oxide,2015,46:192-203.
[2]Kusche-Vihrog K,Schmitz B,Brand E.Salt controls endothelial and vascular phenotype[J].Pflugers Arch,2015,467(3):499-512.
[3]Hypertension in pregnancy.Report of the American College of Obstetricians and Gynecologists'Task Force on Hypertension in Pregnancy[J].Obstet Gynecol,2013,122(5):1122-1131.
[4]Ghulmiyyah L,Sibai B.Maternal mortality from preeclampsia/eclampsia[J].Semin Perinatol,2012,36(1):56-59.
[5]Paneni F,Beckman JA,Creager MA,et al.Diabetes and vascular disease:pathophysiology,clinical consequences,and medical therapy:partⅠ[J].Eur Heart J,2013,34(31):2436-2443.
[6]Puissant C,Abraham P,Durand S,et al.[Endothelial function:role,assessment and limits][J].J Mal Vasc,2014,39(1):47-56.
[7]Soobryan N,Murugesan S,Phoswa W,et al.The effects of silde nafil citrate on uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of pre-eclampsia[J].Eur J Pharmacol,2017,795:101-107.
[8]Shu W,Shu W,Li H,et al.Evaluation of blood vessel injury,oxidative stress and circulating inflammatory factors in an L-NAME-induced preeclampsia-like rat model[J].Exp Ther Med,2018,16(2):585-594.
[9]Briet M,Collin C,Laurent S,et al.Endothelial function and chronic exposure to air pollution in normal male subjects[J].Hypertension,2007,50(5):970-976.
[10]Geelhoed JJ,Fraser A,Tilling K,et al.Preeclampsia and gestat ional hypertension are associated with childhood blood press ure independently of family adiposity measures:the Avon Long itudinal Study of Parents and Children[J].Circulation,2010,122(12):1192-1199.
[11]Chaiworapongsa T,Chaemsaithong P,Yeo L,et al.Pre-eclampsia part 1:current understanding of its pathophy siology[J].Nat Rev Nephrol,2014,10(8):466-480.
[12]Du Pont JJ,Greaney JL,Wenner MM,et al.High dietary sodium intake impairs endothelium-dependent dilation in healthy saltresistant humans[J].J Hypertens,2013,31(3):530-536.
[13]Cappuccio FP.Cardiovascular and other effects of salt consumption[J].Kidney Int Suppl(2011),2013,3(4):312-315.
[14]Oberleithner H,Riethmuller C,Schillers H,et al.Plasma sodium stiffens vascular endothelium and reduces nitric oxide release[J].Proc Natl Acad Sci U S A,2007,104(41):16281-16286.
[15]Paniagua OA,Bryant MB,Panza JA.Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature:diminished activity in hypertensive and hypercholesterolemic patients[J].Circulation,2001,103(13):1752-1758.
[16]Feng W,Ying WZ,Aaron KJ,et al.Transforming growth factor-beta mediates endothelial dysfunction in rats during high salt intake[J].Am J Physiol Renal Physiol,2015,309(12):F1018-F1025.
[17]Koleganova N,Piecha G,Ritz E,et al.Both high and low maternal salt intake in pregnancy alter kidney development in the offspring[J].Am J Physiol Renal Physiol,2011,301(2):F344-F354.
[18]杨宁,李玉明.从多哈理论看妊娠期高血压疾病对子代心血管健康的重大影响[J].中国医学前沿杂志(电子版),2016,8(2):14-17.
[19]李玉明,杨宁.关注生命早期心血管病风险暴露及初始预防[J].中华心血管病杂志,2017,45(4):274-276.