Department of Physiology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, 430030, China.
School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2019 Feb;39(1):21-27. doi: 10.1007/s11596-019-1995-5. Epub 2019 Mar 13.
Increased use of pyrethroids and the exposure to pyrethroids for pregnant women and children have raised the concerns over the potential effect of pyrethroids on developmental cardiotoxicity and other abnormalities. The purpose of this study was to investigate whether long term perinatal deltamethrin exposure altered embryonic cardiac electrophysiology in mice. Pregnant mice were administered with 0 or 3 mg/kg of deltamethrin by gavage daily from gestational day (gd) 10.5 to gd 17. 5. Whole cell patch-clamp technique was used in electrophysiological study, and real time RT-PCR was applied to analyze the molecular changes for the electrophysiological properties. Deltamethrin exposure resulted in increased mortality of pregnant mice and decreased viability of embryos. Moreover, deltamethrin slowed the maximum depolarization velocity (Vmax), prolonged the action potential duration (APD) and depolarized the maximum diastolic potential (MDP) of embryonic cardiomyocytes. Additionally, perinatal deltamethrin exposure decreased the mRNA expression of Na channel regulatory subunit Navβ1, inward rectifier K channel subunit Kir2.1, and delayed rectifier K channel subunit MERG while the L-type Ca channel subunit, Cav1.2 expression was increased. On the contrary, deltamethrin administration did not significantly alter the regulation of β-adrenergic or muscarinic receptor on embryonic cardiomyocytes. In conclusion, deltamethrin exposure at perinatal stage significantly alters mRNA expression of embryonic cardiac ion channels and therefore influences embryonic cardiac electrophysiological properties. This highlights the need to understand the persistent effects of pyrethroid exposure on cardiac function during embryonic development due to potential for cardiac arrhythmogenicity.
孕期和儿童接触拟除虫菊酯的增加引发了人们对其潜在发育性心脏毒性和其他异常作用的担忧。本研究旨在探究围产期长期使用溴氰菊酯是否会改变小鼠胚胎心脏的电生理特性。妊娠第 10.5 天至第 17.5 天，通过灌胃给予孕鼠 0 或 3mg/kg 的溴氰菊酯。采用全细胞膜片钳技术进行电生理研究，实时 RT-PCR 用于分析电生理特性的分子变化。溴氰菊酯暴露导致孕鼠死亡率增加，胚胎活力降低。此外，溴氰菊酯减慢了胚胎心肌细胞的最大去极化速度（Vmax），延长了动作电位时程（APD），并使最大舒张期电位（MDP）去极化。此外，围产期溴氰菊酯暴露降低了钠通道调节亚基 Navβ1、内向整流钾通道亚基 Kir2.1 和延迟整流钾通道亚基 MERG 的 mRNA 表达，而 L 型钙通道亚基 Cav1.2 的表达增加。相反，溴氰菊酯给药并未显著改变胚胎心肌细胞β-肾上腺素能或毒蕈碱受体的调节。总之，围产期溴氰菊酯暴露显著改变了胚胎心脏离子通道的 mRNA 表达，从而影响了胚胎心脏的电生理特性。这突显了由于潜在的心律失常作用，需要了解拟除虫菊酯暴露对胚胎发育中心脏功能的持续影响。
