Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.

Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.
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急性气管内吸入暴露于异氟烷引起的对大鼠心脏组织转录组的纵向影响。

DOI:
10.1371/journal.pone.0257241
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Cohen MD
Cohen MD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Park SH;Lu Y;Shao Y;Prophete C;Horton L;Sisco M;Lee HW;Kluz T;Sun H;Costa M;Zelikoff J;Chen LC;Cohen MD

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异氟醚(ISO)是一种广泛使用的吸入麻醉剂,在啮齿动物和手术期间的人类实验中使用。虽然ISO尚未被报道会产生持久的副作用,但目前尚不清楚ISO是否会影响某些组织的基因调控,包括心脏。这些变化可能会对易患心力衰竭/其他心脏异常的患者使用这种麻醉剂产生重要影响。为了测试ISO是否可以改变心脏组织中的基因调控/表达,以及这种变化是否随着时间的推移而可逆、延长或迟发,SHR(自发性高血压)大鼠通过气管内吸入97.5%空气/2.5%ISO混合物连续两天(2小时/d)。对照组大鼠只呼吸过滤后的空气。在暴露后第1、30、240和360天,收集大鼠心脏,从左心室提取总RNA,用于整体基因表达分析。数据显示,在暴露后的所有时间点,差异表达基因(DEG)对ISO的反应(与幼稚对照相比)。数据显示,在第1天和第30天,急性ISO暴露导致与创伤、局部免疫功能、炎症和昼夜节律调节相关的DEG;这些影响在第240天消失。在第360天,ISO诱导的其他显著增加的DEG;这些包括与细胞信号、分化和迁移、细胞外基质组织、细胞-底物黏附、心脏发育和血压调节相关的基因表达的变化。在第240天和第360天对一致性DEG的检查表明,迟发性DEG反映了ISO潜在的长期影响;这些DEG包括与氧化磷酸化、核糖体、血管生成、线粒体翻译延长和局部粘连相关的DEG。总之,这些数据表明,急性重复暴露ISO可能会对心脏中的基因表达/调节产生不同的影响。虽然有些变化会自行解决,但其他变化似乎持续时间较长或发病较晚。这种变化是否发生在所有的大鼠模型或人类身上仍有待调查。
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.
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