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溴氰菊酯通过促进内质网应激和线粒体功能障碍诱导鹌鹑脑神经元凋亡。

Deltamethrin induces apoptosis in cerebrum neurons of quail via promoting endoplasmic reticulum stress and mitochondrial dysfunction.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, China.

出版信息

Environ Toxicol. 2022 Aug;37(8):2033-2043. doi: 10.1002/tox.23548. Epub 2022 Apr 21.

DOI:10.1002/tox.23548
PMID:35446475
Abstract

Deltamethrin (DLM) is a widely used and highly effective insecticide. DLM exposure is harmful to animal and human. Quail, as a bird model, has been widely used in the field of toxicology. However, there is little information available in the literature about quail cerebrum damage caused by DLM. Here, we investigated the effect of DLM on quail cerebrum neurons. Four groups of healthy quails were assigned (10 quails in each group), respectively given 0, 15, 30, and 45 mg/kg DLM by gavage for 12 weeks. Through the measurements of quail cerebrum, it was found that DLM exposure induced obvious histological changes, oxidative stress, and neurons apoptosis. To further explore the possible molecular mechanisms, we performed real-time quantitative PCR to detect the expression of endoplasmic reticulum (ER) stress-related mRNA such as glucose regulated protein 78 kD, activating transcription factor 6, inositol requiring enzyme, and protein kinase RNA (PKR)-like ER kinase. In addition, we detected ATP content in quail cerebrum to evaluate the functional status of mitochondria. The study showed that DLM exposure significantly increased the expression of ER stress-related mRNA and decreased ATP content in quail cerebrum tissues. These results suggest that chronic exposure to DLM induces apoptosis of quail cerebrum neurons via promoting ER stress and mitochondrial dysfunction. Furthermore, our results provide a novel explanation for DLM-induced apoptosis of avian cerebrum neurons.

摘要

溴氰菊酯(DLM)是一种广泛使用且高效的杀虫剂。DLM 暴露对动物和人类都是有害的。鹌鹑作为一种鸟类模型,已被广泛应用于毒理学领域。然而,关于 DLM 对鹌鹑大脑神经元损伤的信息在文献中很少见。在这里,我们研究了 DLM 对鹌鹑大脑神经元的影响。将四组健康鹌鹑(每组 10 只)分别灌胃 0、15、30 和 45mg/kg 的 DLM,持续 12 周。通过对鹌鹑大脑的测量,发现 DLM 暴露会引起明显的组织学变化、氧化应激和神经元凋亡。为了进一步探索可能的分子机制,我们通过实时定量 PCR 检测内质网(ER)应激相关 mRNA 的表达,如葡萄糖调节蛋白 78kD、激活转录因子 6、肌醇需求酶和蛋白激酶 RNA(PKR)样 ER 激酶。此外,我们还检测了鹌鹑大脑中的 ATP 含量,以评估线粒体的功能状态。研究表明,DLM 暴露会显著增加 ER 应激相关 mRNA 的表达,并降低鹌鹑大脑组织中的 ATP 含量。这些结果表明,慢性暴露于 DLM 通过促进 ER 应激和线粒体功能障碍诱导鹌鹑大脑神经元凋亡。此外,我们的结果为 DLM 诱导禽类大脑神经元凋亡提供了新的解释。

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