研究动态
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非酒精性脂肪性肝病与药物性肝损伤相互作用的拟-LD-有靶向性和ONOO-响应性荧光探针。

Quasi-LD-Targeted and ONOO--Responsive Fluorescent Probe for Investigating the Interaction of Nonalcoholic Fatty Liver with Drug-Induced Liver Injury.

发表日期:2023 Mar 28
作者: Nannan Wang, Xiaoyan Lu, Jiamin Wang, Han Wang, Bo Zhang, Weili Zhao, Jian Zhang
来源: Disease Models & Mechanisms

摘要:

肝脏脂滴(LDs)和过氧亚硝酸(ONOO-)水平与非酒精性脂肪肝病(NAFLD)密切相关。此外,一些药物引起的肝损伤(DILI)常与ONOO-有关。在这里,我们构建和筛选了准LDs靶向和ONOO--响应荧光探针MBDP-Py+,以研究NAFLD与DILI的相互作用。通过监测ONOO-水平的上调和LDs的积累,MBDP-Py+比组织染色和血清标记检测在评估NAFLD早期毒性和诊断抗癌DILI方面更为敏感和高效。更重要的是,荧光信号的敏感增强表明,在NAFLD不同阶段中,与DILI的结合会导致肝损伤的主导因素不同。随着NAFLD程度的加深,两者的协同作用将导致更严重的肝损伤。
Hepatic lipid droplets (LDs) and peroxynitrite (ONOO-) levels are closely related to nonalcoholic fatty liver disease (NAFLD). Additionally, some drug-induced liver injury (DILI) is often associated with ONOO-. Here, we constructed and screened the quasi-LDs-targeted and ONOO--responsive fluorescent probe MBDP-Py+ to investigate the interaction of NAFLD with DILI. By monitoring the upregulation of the ONOO- levels and the accumulation of LDs, MBDP-Py+ was more sensitive and efficient than tissue staining and serum markers detection in evaluating the early toxicity of NAFLD and diagnosing the anticancer-DILI. More importantly, the sensitive enhancement of fluorescence signals demonstrated that in different stages of NAFLD, the dominant element of liver injury was different in the NAFLD combined with DILI mice models. As the degree of NAFLD deepens, the synergistic effect of the two will lead to more serious liver damage.