肝纤维化(HF)是由持续性炎症引起的,与肝脏氧化应激密切相关。过氧亚硝酸盐(ONOO-)在HF中显著升高,这将被认为是诊断HF的潜在生物标志物。研究表明,高尔基体中的ONOO-可以在HF中过量产生,它可以通过引发高尔基体氧化应激诱导肝细胞损伤。同时,ONOO-抑制剂可以通过抑制高尔基体ONOO-,但是到目前为止,没有高尔基靶向荧光探针可用于诊断和评估HF的治疗反应通过感测高尔基ONOO-。为此,我们报道了一种比率荧光探针,高尔基-PER,通过监测高尔基体ONOO-来诊断和评估HF的治疗反应。高尔基-PER显示出令人满意的灵敏度,低检测限,和对ONOO-的特殊选择性。结合优异的生物相容性和良好的高尔基靶向能力,高尔基-PER进一步用于定量监测高尔基ONOO-波动和筛选活细胞中多酚的ONOO-抑制剂。同时,用高尔基-PER作为探测器,首次准确显示了高尔基体ONOO-在HF中的过表达和HF对筛选的迷迭香酸的治疗反应。此外,筛选出的RosA对HF有显著的治疗效果,这可能是HF治疗的新策略。这些结果证明了高尔基-PER监测发生的可行性,发展,和个性化的HF治疗反应。
Hepatic fibrosis (HF) is caused by persistent inflammation, which is closely associated with hepatic oxidative stress. Peroxynitrite (ONOO-) is significantly elevated in HF, which would be regarded as a potential biomarker for the diagnosis of HF. Research has shown that ONOO- in the Golgi apparatus can be overproduced in HF, and it can induce hepatocyte injury by triggering Golgi oxidative stress. Meanwhile, the ONOO- inhibitors could effectively relieve HF by inhibiting Golgi ONOO-, but as yet, no Golgi-targetable fluorescent probe available for diagnosis and assessing treatment response of HF through sensing Golgi ONOO-. To this end, we reported a ratiometric fluorescent probe, Golgi-PER, for diagnosis and assessing treatment response of HF through monitoring the Golgi ONOO-. Golgi-PER displayed satisfactory sensitivity, low detection limit, and exceptional selectivity to ONOO-. Combined with excellent biocompatibility and good Golgi-targeting ability, Golgi-PER was further used for ratiometric monitoring the Golgi ONOO- fluctuations and screening of ONOO- inhibitors from polyphenols in living cells. Meanwhile, using Golgi-PER as a probe, the overexpression of Golgi ONOO- in HF and the treatment response of HF to the screened rosmarinic acid were precisely visualized for the first time. Furthermore, the screened RosA has a remarkable therapeutic effect on HF, which may be a new strategy for HF treatment. These results demonstrated the practicability of Golgi-PER for monitoring the occurrence, development, and personalized treatment response of HF.