aldosterone cardiomegaly cardiomyopathies mice peripartum period
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摘要

BACKGROUND:The maternal circulatory system and hormone balance both change dynamically during pregnancy, delivery, and the postpartum period. Although atrial natriuretic peptides and brain natriuretic peptides produced in the heart control circulatory homeostasis through their common receptor, NPR1, the physiologic and pathophysiologic roles of endogenous atrial natriuretic peptide/brain natriuretic peptide in the perinatal period are not fully understood.
METHODS:To clarify the physiologic and pathophysiologic roles of the endogenous atrial natriuretic peptide/brain natriuretic peptide-NPR1 system during the perinatal period, the phenotype of female wild-type and conventional or tissue-specific Npr1-knockout mice during the perinatal period was examined, especially focusing on maternal heart weight, blood pressure, and cardiac function.
RESULTS:In wild-type mice, lactation but not pregnancy induced reversible cardiac hypertrophy accompanied by increases in fetal cardiac gene mRNAs and ERK1/2 (extracellular signaling-regulated kinase) phosphorylation. Npr1-knockout mice exhibited significantly higher plasma aldosterone level than did wild-type mice, severe cardiac hypertrophy accompanied by fibrosis, and left ventricular dysfunction in the lactation period. Npr1-knockout mice showed a high mortality rate over consecutive pregnancy-lactation cycles. In the hearts of Npr1-knockout mice during or after the lactation period, an increase in interleukin-6 mRNA expression, phosphorylation of signal transducer and activator of transcription 3, and activation of the calcineurin-nuclear factor of the activated T cells pathway were observed. Pharmacologic inhibition of the mineralocorticoid receptor or neuron-specific deletion of the mineralocorticoid receptor gene significantly ameliorated cardiac hypertrophy in lactating Npr1-knockout mice. Anti-interleukin-6 receptor antibody administration tended to reduce cardiac hypertrophy in lactating Npr1-knockout mice.
CONCLUSIONS:These results suggest that the characteristics of lactation-induced cardiac hypertrophy in wild-type mice are different from exercise-induced cardiac hypertrophy, and that the endogenous atrial natriuretic peptide/brain natriuretic peptide-NPR1 system plays an important role in protecting the maternal heart from interleukin-6-induced inflammation and remodeling in the lactation period, a condition mimicking peripartum cardiomyopathy.

译文

背景: 母体循环系统和激素平衡在妊娠、分娩和产后都动态变化。虽然心内产生的心钠素和脑钠素通过它们共同的受体 NPR1 控制循环稳态, 内源性心房钠尿肽/脑钠尿肽在围生期的生理和病理生理作用尚不完全清楚。
方法: 为了阐明内源性心钠素/脑钠 peptide-NPR1 系统在围生期的生理和病理生理作用, 研究了围产期雌性野生型和常规或组织特异性 Npr1-knockout 小鼠的表型,特别关注母体心脏重量、血压和心脏功能。
结果: 在野生型小鼠中,哺乳期而不是妊娠诱导了可逆的心肌肥大,伴随着胎儿心脏基因 mrna 和 ERK1/2 (细胞外信号调节激酶) 磷酸化的增加。Npr1-knockout 小鼠的血浆醛固酮水平明显高于野生型小鼠,严重的心肌肥大伴纤维化,哺乳期左心室功能障碍。Npr1-knockout 小鼠在连续的妊娠-哺乳期表现出高死亡率。在哺乳期或之后的 Npr1-knockout 小鼠心脏中,interleukin-6 mRNA 表达、信号转导子和转录激活子 3 的磷酸化增加, 观察到活化 T 细胞通路的钙调神经磷酸酶-核因子的激活。药理抑制盐皮质激素受体或神经元特异性删除盐皮质激素受体基因可显著改善哺乳期 Npr1-knockout 小鼠的心肌肥大。Anti-interleukin-6 受体抗体给药倾向于减少哺乳期 Npr1-knockout 小鼠的心肌肥厚。
结论: 这些结果表明野生型小鼠哺乳期诱导的心肌肥厚的特征不同于运动诱导的心肌肥厚, 并且内源性心钠素/脑钠 peptide-NPR1 系统在哺乳期保护母体心脏免受 interleukin-6-induced 炎症和重构方面发挥着重要作用,哺乳期是一种类似于围产期心肌病的情况。

peripartum cardiomyopathy

重症 心肌病 疾病
概述  :  

围产期心肌病是发生于妊娠最末1月或产后前5个月不能分类于任何已知心脏病的特发性心力衰竭,其发病较为突然,急性期病死率可达10%。但如果给予及时诊断和治疗则可明显降低病死率,大部分围产期心肌病患者可在3~6个月内得到恢复。   病理机制 目前尚不清楚围产期心肌病的致病原因。虽然初产妇和年龄>30岁的孕妇、双胎妊娠、高血压病史、先兆子痫以及子痫均与高围产期心肌病发病率相关,但并无因果关系。最近的研究提示炎症和遗传性因素在围产

peripartum

释义   分娩前后;围产期

例句   To evaluate the clinical factors that affect the prognosis of peripartum cardiomyopathy.目的探讨影响围生期心肌病预后的临床因素。

 

cardiomyopathy 英 [,kɑːdɪəʊmaɪ'ɒpəθɪ] 美 [,kɑrdɪomaɪ'ɑpəθi]

释义   n. (尤指原发性的)心肌症,心肌病

例句   Prevention of dilated cardiomyopathy appears to be possible through regular supplementation with these two amino acids.通过定期补充这两种氨基酸似乎可以预防扩张型心肌病。

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