TNF-α/NF-κB介导的线粒体凋亡途径在蜂毒肽致急性肾损伤中的作用机制研究

Melittin, a major component of bee venom, has been considered to play a key role in acute kidney injury (AKI) following bee stings. Previous studies have showed that TNF-α/TNFR1 and NF-κB signal pathways are closely linked to cell apoptosis. In recent years, the important part of apoptosis plays in AKI has been more recognized. However, the relationship between melittin and renal tubular cell apoptosis has never been explored. Our previous work has demonstrated in mice that melittin could induce renal tubular cell apoptosis, in which mitochondrial apoptotic pathway may play an important role. Therefore, we speculate that AKI following bee stings may be closely related to renal tubular cell apoptosis via mitochondrial apoptotic pathway, which is triggered by TNF-α/TNFR1 signal pathway and regulated by NF-κB signal pathway. In this study, we will investigate the effect of meliitin on renal tubular cells, and the role TNF-α/NF-κB pathways play in melittin induced AKI by using RT-qPCR, western-blot, EMSA and siRNA methods. It will help to clarify the molecular mechanism of AKI following bee stings, and may provide new therapeutic targets for that.

蜂毒肽是蜂毒的主要致病成分，在蜂蛰伤致急性肾损伤（AKI）中扮演着重要角色。目前较多研究均指出TNF-α/TNF-R1信号系统及NF-κB信号途径均与细胞凋亡密切相关，而肾小管上皮细胞凋亡在AKI的发生发展中发挥着重要作用，亦是潜在的干预靶点。蜂毒肽与肾小管上皮细胞凋亡的关系尚无研究，我们的前期工作已证实小鼠模型中蜂毒肽可导致肾小管上皮细胞凋亡，其中线粒体凋亡途径可能发挥着关键作用。据此我们提出，蜂毒肽通过激活TNF-α介导的线粒体凋亡途径是AKI发生发展的重要机制，并受到NF-κB信号途径的调控。为了证实这一科学假说，本实验将应用RT-qPCR、western-blot、EMSA及siRNA基因沉默等技术，拟从整体及细胞两个层次探讨蜂毒肽对肾小管上皮细胞凋亡的影响及TNF-α/NF-κB相关信号转导通路。本课题将从新的视角阐明蜂毒肽致AKI的分子机制，为蜂蛰伤致AKI的防治提供新的靶点。

蜂毒肽是蜂毒的主要致病成分，在蜂蛰伤致急性肾损伤（AKI）中扮演着重要角色。目前较多研究均指出TNF-α/TNF-R1信号系统及NF-κB信号途径均与细胞凋亡密切相关，而肾小管上皮细胞凋亡在AKI的发生发展中发挥着重要作用，亦是潜在的干预靶点。蜂毒肽与肾小管上皮细胞凋亡的关系尚无研究，我们的前期工作已证实小鼠模型中蜂毒肽可导致肾小管上皮细胞凋亡，其中线粒体凋亡途径可能发挥着关键作用。据此我们提出，蜂毒肽通过激活TNF-α介导的线粒体凋亡途径是AKI发生发展的重要机制，并受到NF-κB信号途径的调控。为了证实这一科学假说，本实验将应用RT-qPCR、western-blot、EMSA及siRNA基因沉默等技术，拟从整体及细胞两个层次探讨蜂毒肽对肾小管上皮细胞凋亡的影响及TNF-α/NF-κB相关信号转导通路。本课题将从新的视角阐明蜂毒肽致AKI的分子机制，为蜂蛰伤致AKI的防治提供新的靶点。