Shi Yan, Hua Qiuju, Li Na, Zhao Min, Cui Yan
Hospital of Nephrology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, China.
Evid Based Complement Alternat Med. 2019 Mar 3;2019:2190847. doi: 10.1155/2019/2190847. eCollection 2019.
Acute kidney injury (AKI) is a critical care syndrome, which is usually associated with sepsis-related endotoxemia. Evodiamine (EVO) is an active ingredient of many traditional medicinal formulations that possess a battery of biological activities. In the study, we aimed to evaluate the potential protective effect of EVO against lipopolysaccharide- (LPS-) induced AKI and cytotoxicity. LPS-resulted pathological injuries were significantly ameliorated by the administration of EVO. EVO reduced the levels of blood urea nitrogen (BUN) and creatinine in LPS-treated rats. EVO also inhibited LPS-induced reduction of cell viability in NRK-52E cells. LPS-resulting increase of TNF and IL-1 in both serum and kidney of rats and NRK-52E cells was inhibited by EVO. LPS-induced increase of P65 NF-B expression was markedly inhibited by EVO. EVO-induced reduction of TNF and IL-1 expression in LPS-treated cells was blocked by overexpression of P65 NF-B. Moreover, the increase of cell viability in LPS-treated cells induced by EVO was remarkably suppressed by overexpression of P65 NF-B. LPS-resulting increase of reactive oxygen species (ROS) production was suppressed by EVO. HO suppressed EVO-induced decrease of P65 NF-B expression and increase of cell viability in LPS-treated NRK-52E cells. Moreover, the antioxidant NAC significantly promoted EVO-induced decrease of P65 NF-B expression and increase of cell viability in LPS-treated NRK-52E cells. In conclusion, EVO had crucial protective effects against LPS-induced AKI and cytotoxicity through the antioxidant activities and thus the inhibition of inflammation. Our data highlight EVO as a potential candidate for the development of new strategies for the treatment of AKI.
急性肾损伤（AKI）是一种危重症综合征，通常与脓毒症相关的内毒素血症有关。吴茱萸碱（EVO）是许多传统药物制剂的活性成分，具有一系列生物活性。在本研究中，我们旨在评估EVO对脂多糖（LPS）诱导的AKI和细胞毒性的潜在保护作用。给予EVO可显著改善LPS所致的病理损伤。EVO降低了LPS处理大鼠的血尿素氮（BUN）和肌酐水平。EVO还抑制了LPS诱导的NRK-52E细胞活力降低。EVO抑制了LPS导致的大鼠血清和肾脏以及NRK-52E细胞中TNF和IL-1的增加。EVO显著抑制了LPS诱导的P65 NF-κB表达增加。P65 NF-κB的过表达阻断了EVO诱导的LPS处理细胞中TNF和IL-1表达的降低。此外，P65 NF-κB的过表达显著抑制了EVO诱导的LPS处理细胞中细胞活力的增加。EVO抑制了LPS导致的活性氧（ROS）生成增加。HO-1抑制了EVO诱导的LPS处理的NRK-52E细胞中P65 NF-κB表达的降低和细胞活力的增加。此外，抗氧化剂NAC显著促进了EVO诱导的LPS处理的NRK-52E细胞中P65 NF-κB表达的降低和细胞活力的增加。总之，EVO通过抗氧化活性进而抑制炎症，对LPS诱导的AKI和细胞毒性具有关键的保护作用。我们的数据突出了EVO作为开发AKI治疗新策略的潜在候选药物。
