College of Chinese Medicine Materials, Jilin Agricultural University, Changchun 130118, China.
Changchun Institute of Technology School of Medicine, Changchun 130600, China.
Int J Biol Macromol. 2019 Dec 1;141:961-987. doi: 10.1016/j.ijbiomac.2019.08.164. Epub 2019 Aug 31.
Acetaminophen (APAP)-induced acute kidney injury (AKI) has turned into a typical reason for clinic obtained renal disappointment. In any case, the advancement of prophylaxis procedures and endorsed treatments for APAP-AKI is restricted. Sika deer antler protein (SDAPR) has a protective effect on drug-induced AKI. The reason for this investigation was to clarify the material premise and atomic instrument of the defensive impact of SDAPR on APAP-induced AKI. We conducted column chromatography on SDAPR extracted with Sephadex G-100 and obtained proteins of 2 different components named sika deer antler protein 1 (SDAP1) and sika deer antler protein 2 (SDAP2), respectively. MTT assay and xCELLigence Real-Time Cell Analysis showed that SDAPR, SDAP1 and SDAP2 had protective effects on APAP-induced cytotoxicity in Human kidney tubular epithelial (HK-2) cells. Therefore, we conducted proteomic analysis on SDAPR, SDAP1 and SDAP2. What's more, we inspected them viability of avoiding renal damage in APAP mice and HK-2 cells model. Contrasted and saline, SDAPR, SDAP1 and SDAP2 pretreatment portion conditionally fundamentally constricted heights in kidney damage Markers and the histological changes of renal cylindrical wounds, diminished the quantity of apoptosis-positive rounded cells, initiated NF-E2 p45-related factor 2 (Nrf2), inhibition Forkhead box O 1 transcription factors (FoxO1) and brought down the degrees of renal oxidative stress and apoptosis prompted by APAP. The above security of SDAPR, SDAP1 and SDAP2 was nullified by the Phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) in HK-2 cells. In this manner, our outcomes exhibit that, SDAPR, SDAP1 and SDAP2 against APAP-induced oxidative stress and apoptosis by initiating Nrf2 and restraint FoxO1 through PI3K/Akt signaling.
对乙酰氨基酚（APAP）诱导的急性肾损伤（AKI）已成为临床获得性肾衰竭的常见原因。然而，APAP-AKI 的预防措施和批准的治疗方法的发展受到限制。梅花鹿鹿茸蛋白（SDAPR）对药物诱导的 AKI 具有保护作用。本研究的目的是阐明 SDAPR 对 APAP 诱导的 AKI 的保护作用的物质前提和原子仪器。我们用 Sephadex G-100 对 SDAPR 进行柱层析，分别得到 2 种不同成分的蛋白质，分别命名为梅花鹿鹿茸蛋白 1（SDAP1）和梅花鹿鹿茸蛋白 2（SDAP2）。MTT 测定和 xCELLigence 实时细胞分析显示，SDAPR、SDAP1 和 SDAP2 对 APAP 诱导的人肾小管上皮细胞（HK-2）细胞的细胞毒性具有保护作用。因此，我们对 SDAPR、SDAP1 和 SDAP2 进行了蛋白质组学分析。此外，我们在 APAP 小鼠和 HK-2 细胞模型中观察了它们对肾损伤的保护作用。与生理盐水相比，SDAPR、SDAP1 和 SDAP2 预处理条件性地基本降低了肾损伤标志物和肾圆柱损伤的组织学变化的高度，减少了凋亡阳性圆形细胞的数量，启动了核因子 E2 p45 相关因子 2（Nrf2），抑制了叉头框 O1 转录因子（FoxO1），降低了 APAP 诱导的肾氧化应激和细胞凋亡程度。在 HK-2 细胞中，PI3K 抑制剂（LY294002）消除了 SDAPR、SDAP1 和 SDAP2 的上述保护作用。因此，我们的研究结果表明，SDAPR、SDAP1 和 SDAP2 通过激活 Nrf2 和抑制 FoxO1 来抑制 PI3K/Akt 信号通路，从而抵抗 APAP 诱导的氧化应激和细胞凋亡。
