左心衰竭小鼠妊娠时左心室的反应及其肥厚重构的病理分子机制  

Cardiac response to pregnancy in a mouse model of left heart failure and its pathological changes on left ventricular remolding

作　　者：徐洪[1] 臧旺福[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院心脏外科,225001

出　　处：《中华临床医师杂志（电子版）》2014年第6期87-93,共7页Chinese Journal of Clinicians(Electronic Edition)

基　　金：2012年上海高校优青科研专项基金(82013011900002)

摘　　要：目的探讨器质性心脏基础疾病左心衰竭合并妊娠时,左心室功能的变化及其肥厚重构的病理分子变化。方法微创主动脉弓缩窄(TAC)建立左心衰竭小鼠,诱导其妊娠,于妊娠晚期超声心动图(TTE)评估心脏结构和功能的变化、病理方法评估测心肌肥厚、间质纤维化以及毛细血管密度,监测器官重量、胎鼠体重、数量以评估左心室反应及其肥厚重构的变化以及对胎鼠的影响。结果重度缩窄sTAC组的妊娠率是62.5%,妊娠期间的死亡率是8.7%,中度缩窄mTAC及假手术组所有小鼠怀孕无死亡,三组中胎鼠的数量和平均体重并无统计学差异(P>0.05);怀孕sTAC小鼠的LVFS%有明显下降(21.6±1.18 vs.15.9±1.41,P<0.05),且左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)进一步扩大(P<0.01);而妊娠sTAC小鼠的LVFS%略有下降至18.1±1.67(P>0.05),其左心室腔并未有进一步明显扩张,且扩张的幅度明显小于未妊娠sTAC小鼠;mTAC小鼠的超声指标均未见明显变化;HE染色发现sTAC组未妊娠小鼠心肌细胞横径明显大于妊娠小鼠(62.04±0.98 vs.48.46±1.33,P<0.05),后者与mTAC妊娠小鼠的心肌细胞横径无明显差异(P>0.05);无论妊娠和非妊娠sTAC小鼠,均显示明显的间质纤维化(P<0.05);而mTAC组和假手术组的纤维化程度均<1%,mTAC或sTAC小鼠,无论有无妊娠,毛细血管密度均有明显下降(P<0.05),未怀孕sTAC小鼠低于怀孕sTAC小鼠(1 675.02±41.15 vs.1 916.91±48.04,P<0.05)。结论妊娠伴随的心血管系统变化会诱使已经衰竭心脏功能进一步恶化,但顺利妊娠分娩仍是完全可能的,其心肌肥厚重构反而轻于未妊娠时,可能机制是高水平的雌激素部分抵消了妊娠状态对心功能的不利影响,延缓心肌肥厚重构的进展,从而有利于心脏收缩功能的保存。Objective To assess cardiac structural responses and the pathological changes of left ventricule （LV） under the compromised conditions of transverse aortic constriction （TAC） induced left heart failure during pregnancy. Methods Based on the successfully established model of pressure overload induced LVH, all operated mice were mated to find out whether these mTAC （moderate TAC） or sTAC （severe TAC） mice can get pregnant or even survive the pregnancy. TTE was deployed again to examine the contractile function of the heart. LV tissues were stained to analyze the interstitial fibrosis, capillary density, and myocyte width to evaluate the status of hypertrophic responses and cardiac remodeling. Maternal and fetal outcomes including maternal death rate, litter size, average body weight of pups were calculated to evaluate the effect of LVH or heart failure on the growth and maturity of mouse fetus in pregnant mice. Results 62.5% of all sTAC mice finally became pregnant with a death rate of 8.7%, while in mTAC group, all mice got pregnant and survived, without maternal death. TTE examination demonstrated that LVFS% in sTAC mice decreased further, especially in non-pregnant sTAC mice, the LVFS% was depressed significantly from 21.6±1.18 to 15.9±1.41 （P〈0.05）, and LV parameters including LVESD and LVEDD increased substantially to （3.73±0.20）mm （P〈0.01） and （4.41± 0.18）mm （P〈0.01）, respectively, which showed an progressively impaired LV contractile function and dilated LV lumen. While LVEDD and LVESD also had noticeable increases in sTAC pregnant mice, but the increases were not statistically significant （P〉0.05）, LVFS%decreased to 18.1±1.67 but no statistical difference （P〉0.05） was found. LVFS%, LVEDD and LVESD of mTAC mice didn＇t have significant changes. Fetal outcomes showed that no significant difference in litter size and average body weight of pups were found in each group, yet, sTAC mice with pathological LV hypertrophy carried more pups with lower avera

关 键 词：妊娠 心力衰竭 小鼠 雌激素类 

分 类 号：R541.6[医药卫生—心血管疾病]