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抑制 Nrf2/p38MAPK 通路可减轻溴氰菊酯诱导鹌鹑肾细胞凋亡和纤维化。

Inhibition of the Nrf2/p38MAPK pathway involved in deltamethrin-induced apoptosis and fibrosis in quail kidney.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin, 150030, China.

出版信息

Food Chem Toxicol. 2021 Sep;155:112382. doi: 10.1016/j.fct.2021.112382. Epub 2021 Jun 30.

DOI:10.1016/j.fct.2021.112382
PMID:34216712
Abstract

Deltamethrin (DLM) is a broad-spectrum and effective pyrethroid insecticide. However, DLM has good residual activity on most surfaces and many insects, so it poses a threat to the environment and health of animals and human. Exposure to DLM can cause kidney injury, but the mechanism is not well understood. Therefore, we investigated the possible mechanism of quail kidney injury induced by chronic exposure to different doses of DLM for 12 weeks. The results showed that chronic exposure to DLM induced apoptosis and fibrosis of quail kidney through the promotion of oxidative stress by down-regulating nuclear factor erythroid 2 related factor 2 (Nrf2), up-regulating the phosphorylation of p38 mitogen-activated protein kinases (p38MAPK). Furthermore, DLM-induced kidney apoptosis in quails as evidenced by increased expression of B-cell lymphoma gene 2-associated X while decreased expression of B-cell lymphoma-extra large. Simultaneously, DLM-induced kidney fibrosis in quails as evidenced by increased expression of fibrosis maker proteins. Overall, the results demonstrate that chronic DLM exposure induces kidney apoptosis and fibrosis via inhibition of the Nrf2/p38MAPK pathway. This study provides a new understanding for the mechanism of DLM-induced quail kidney injury and also provides a theoretical basis for treatment of the DLM poisoning.

摘要

溴氰菊酯(DLM)是一种广谱、高效的拟除虫菊酯类杀虫剂。然而,DLM 在大多数表面和许多昆虫上具有良好的残留活性,因此对环境和动物及人类的健康构成威胁。接触 DLM 会导致肾脏损伤,但机制尚不清楚。因此,我们研究了慢性暴露于不同剂量 DLM 12 周对鹌鹑肾脏损伤的可能机制。结果表明,慢性暴露于 DLM 通过下调核因子红细胞 2 相关因子 2(Nrf2)、上调 p38 丝裂原活化蛋白激酶(p38MAPK)磷酸化来促进氧化应激,诱导鹌鹑肾脏细胞凋亡和纤维化。此外,鹌鹑肾脏细胞凋亡的证据是 B 细胞淋巴瘤基因 2 相关 X 蛋白表达增加,而 B 细胞淋巴瘤-extra large 蛋白表达减少。同时,DLM 诱导鹌鹑肾脏纤维化的证据是纤维化标志物蛋白表达增加。总的来说,这些结果表明,慢性 DLM 暴露通过抑制 Nrf2/p38MAPK 通路诱导肾脏细胞凋亡和纤维化。这项研究为 DLM 诱导鹌鹑肾脏损伤的机制提供了新的认识,也为 DLM 中毒的治疗提供了理论依据。

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