Department of Clinic Pathology, Weifang Medical University, China.
Neurologic Disorders and Regeneration Repair Lab of Shandong Higher Education, Weifang Medical University, China.
J Toxicol Sci. 2020;45(9):589-598. doi: 10.2131/jts.45.589.
Acute mercury chloride (HgCl) poisoning may lead to kidney injury, but the underlying mechanism remains largely unknown. Endoplasmic reticulum (ER) stress plays a role in some heavy metal poisoning. Whether it mediates kidney injury in acute HgCl poisoning remains unknown. In this study, we examined the kidney injury and the corresponding ER stress in the mouse model of different doses of acute HgCl poisoning. To further confirm the role of ER stress, we tested the effects of its chemical chaperone [4-phenylbutyric acid (4-PBA)]. The results revealed that acute HgCl poisoning caused more severe kidney injury with dose on and activated ER stress, as indicated by increased expression of GRP78 and CHOP. Inhibition of ER stress restored the functional and morphological changes of kidneys, and partly attenuated renal tubular epithelial cell apoptosis. In summary, ER stress contributes to the acute kidney injury following HgCl poisoning, and inhibition of ER stress may alleviate the kidney injury via reducing apoptosis.
急性氯化汞（HgCl）中毒可导致肾脏损伤，但其中的具体机制仍不清楚。内质网（ER）应激在某些重金属中毒中发挥作用。它是否介导急性 HgCl 中毒所致的肾脏损伤尚不清楚。在这项研究中，我们检测了不同剂量急性 HgCl 中毒小鼠模型的肾脏损伤和相应的 ER 应激情况。为了进一步证实 ER 应激的作用，我们测试了其化学伴侣[4-苯基丁酸（4-PBA）]的作用。结果表明，急性 HgCl 中毒导致更严重的肾脏损伤，随着剂量的增加，内质网应激被激活，GRP78 和 CHOP 的表达增加。抑制 ER 应激恢复了肾脏的功能和形态变化，并部分减轻了肾小管上皮细胞凋亡。综上所述，ER 应激导致 HgCl 中毒后的急性肾损伤，抑制 ER 应激可能通过减少细胞凋亡来减轻肾脏损伤。
