Yi Shanyong, Mai Tingting, Fang Ying, Tian Qishuo, Zhao Shuquan
Xinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
J Biochem Mol Toxicol. 2025 Jan;39(1):e70101. doi: 10.1002/jbt.70101.
With the gradual emergence of xylazine as a street drug, incidents of xylazine poisoning are now occurring worldwide. However, it remains unknown whether long-term exposure to xylazine causes nonalcoholic fatty liver disease (NAFLD). In the present study, the rats were injected with xylazine intraperitoneally for 28 consecutive days, and then serum and liver tissues were collected for analysis. Weight loss was observed in the 40 mg/kg group and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. Histopathologic examination showed hepatic steatosis, necrosis, and fibrosis. By mRNA sequencing, 192 upregulated genes and 277 downregulated genes were found in the 40 mg/kg group, and the PPAR signaling pathway was ranked first in the KEGG pathway analysis. Four genes in the PPAR signaling pathway, Fabp5, Acox2, and Cpt2, were also verified in the 40 mg/kg group by RT-qPCR analysis and western blot. Our results demonstrated that long-term injection of xylazine causes NAFLD and the PPAR signaling pathway plays a core role in the process of xylazine-associated liver injury.
随着赛拉嗪作为一种街头毒品逐渐出现，赛拉嗪中毒事件目前正在全球范围内发生。然而，长期接触赛拉嗪是否会导致非酒精性脂肪性肝病（NAFLD）仍不清楚。在本研究中，大鼠连续28天腹腔注射赛拉嗪，然后收集血清和肝脏组织进行分析。在40mg/kg组中观察到体重减轻，并且观察到天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平升高。组织病理学检查显示肝脂肪变性、坏死和纤维化。通过mRNA测序，在40mg/kg组中发现192个上调基因和277个下调基因，并且在KEGG通路分析中PPAR信号通路排名第一。通过RT-qPCR分析和蛋白质印迹法在40mg/kg组中也验证了PPAR信号通路中的四个基因，即Fabp5、Acox2和Cpt2。我们的结果表明，长期注射赛拉嗪会导致NAFLD，并且PPAR信号通路在赛拉嗪相关肝损伤过程中起核心作用。
