长期高铜暴露通过影响线粒体自噬和细胞焦亡诱导大鼠肝组织损伤

doi:10.11843/j.issn.0366-6964.2022.12.034

Abstract

Abstract: The mechanism of high levels of copper on liver injury in rats was investigated in this research. One hundred and twenty SD rats were randomly divided into 5 groups, including control group, high level copper group I, high level copper group Ⅱ, high level copper group Ⅲ and high level copper group Ⅳ. The liver tissues were collected from the rats which were continuously intragastric administration of 0, 20, 40, 80 and 160 mg·kg^-1 copper for 63 days, respectively. The copper content in liver was determined by ICP-MS, and the pathological changes of liver were observed by pathological sections. The mitochondrial morphology and mitophagosomes were observed by transmission electron microscopy (TEM). The mRNA and protein expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18, Pink1, Parkin, LCB3 and p62 in liver were detected by RT-qPCR and Western blot, respectively. The results showed that the Cu content in liver exhibited a significant dose-dependent effect with increased copper concentration, and long-term exposure to high levels of copper would cause significant structural damage and pathological changes in liver. With the increase of copper exposure level, the levels of mitophagy and pyroptosis decreased after initially increasing. Compared with the control group, the mRNA and protein expression levels of mitophagy-related genes and proteins PINK1 and LC3II/LC3I in high level copper group II and high level copper group III increased significantly (P<0.05). The mRNA and protein expressions of p62 in high level copper group Ⅱ were significantly decreased (P<0.05), and the mRNA and protein expressions of NLRP3, Caspase-1, GSDMD and IL-1β were significantly increased in high level copper group III (P<0.05), but down regulated in high level copper group IV. High levels of copper exposure could induce liver injury in rats by affecting mitophagy and pyroptosis.

Key words: copper, rat, liver, pyroptosis, mitophagy

CLC Number:

S856.9

LIANG Wenqing, LIU Zhonghua, CHANG Xiaoyue, HE Ting, CHEN Jia, MA Xiaoli, TANG Zhaoxin, YU Wenlan. Long-term Exposure to High Levels of Copper Induced Liver Injury in Rats by Affecting Mitophagy and Pyroptosis[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(12): 4490-4500.

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Long-term Exposure to High Levels of Copper Induced Liver Injury in Rats by Affecting Mitophagy and Pyroptosis

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