Yan Hui, Xiang Ping, Zhang Jingshuo, Xie Liqi, Shen Min
Shanghai Key Laboratory of Forensic Science, Shanghai Forensic Platform, Department of Forensic Toxicology, Academy of Forensic Science, Shanghai, China.
College of Pharmaceutical Sciences, Soochow Universtity, Suzhou, Jiangsu, China.
Forensic Sci Res. 2017 Dec 21;5(4):309-321. doi: 10.1080/20961790.2017.1405565.
To elucidate the toxic mechanism of snake venom at the protein level, proteomics technology was applied to investigate the effect of venom on circulation in the mammalian body. Temporal proteomic analysis was performed to profile the dynamic changes in the sera of Sprague-Dawley rats administered with Chinese cobra venom or saline. Using 8-plex iTRAQ analysis, 392 and 636 serum proteins were identified to be linearly upregulated or downregulated over time in the low-dose group and high-dose group, respectively. These proteins were mainly associated with the acute phase response pathway, complement system, and liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor (FXR)/RXR activation pathways. Compared with the low-dose group, the immune response and integrin pathways were inhibited in the high-dose group, although no obvious effect was observed. With consistently higher or lower expression in the high-dose group compared to the low-dose group throughout the whole process of venom poisoning, two proteins, Kininogen-1 (KNG1) and orosomucoid 1 (ORM1), which are involved in metabolism and immune response, occupied a core position in the pathway network and are considered venom dose-dependent biomarker candidates.
为了在蛋白质水平阐明蛇毒的毒性机制，应用蛋白质组学技术研究蛇毒对哺乳动物体内循环的影响。进行了时间蛋白质组学分析，以描绘给予中华眼镜蛇毒或生理盐水的Sprague-Dawley大鼠血清中的动态变化。使用8重iTRAQ分析，低剂量组和高剂量组中分别有392和636种血清蛋白被鉴定为随时间呈线性上调或下调。这些蛋白质主要与急性期反应途径、补体系统以及肝X受体（LXR）/视黄酸X受体（RXR）和法尼醇X受体（FXR）/RXR激活途径相关。与低剂量组相比，高剂量组中免疫反应和整合素途径受到抑制，尽管未观察到明显影响。在整个蛇毒中毒过程中，高剂量组中始终比低剂量组有更高或更低的表达，两种参与代谢和免疫反应的蛋白质，激肽原-1（KNG1）和类粘蛋白1（ORM1），在通路网络中占据核心位置，被认为是蛇毒剂量依赖性生物标志物候选物。
