基于LncRNA769044-ceRNA-miR1679对靶点STAT1的调控探讨姜黄素干预鸡AFB1性肝细胞程序性坏死的分子机制

鸡黄曲霉毒素B1（AFB1）慢性中毒逐年上升，且缺乏安全有效防治药物。课题组前期研究表明：细胞程序性坏死和炎症是鸡AFB1性肝损伤的主要病理形式，姜黄素干预能显著减轻AFB1性肝损伤。同时发现LncRNA769044、miR1679及靶基因STAT1可能是鸡AFB1性肝损伤及姜黄素干预过程中起关键作用的调控网络，但其具体分子机制尚不清楚。因此，申请人假设：姜黄素是通过LncRNA769044-ceRNA-miR1679-STAT1调控网络干预鸡AFB1性肝损伤。本项目通过建立体内外AFB1性肝损伤模型和姜黄素干预模型，采用RNA敲除和过表达技术、双荧光素酶报告基因检测等技术，明确LncRNA769044-miR1679-STAT1相互调控的机制，并阐明该调控网络在姜黄素干预鸡AFB1性肝细胞程序性坏死和炎症中的分子作用机制，为AFB1性肝损伤的有效防治及发现新靶点提供新思路和理论依据。

AFB1 chronic poisoning of chicken has been increasing year by year which lacks safe and effective preventive drugs. Our previous researches showed that cell necroptosis and inflammation are the main pathological forms of chicken liver injury induced by AFB1 and curcumin can significantly alleviate AFB1 induced liver injury. Meanwhile, previous studies also found that LncRNA769044, miR1679 and target gene STAT1 may be the key regulatory network in curcumin alleviating AFB1 induced liver injury, however the specific molecular mechanism still unclear. Therefore, the following hypothesis is proposed: curcumin attenuate AFB1-induced chicken liver damage via regulating the LncRNA769044 as ceRNA to participate in regulation of miR1679-STAT1 network. Base on the cases model of established liver injury induced by AFB1 exposure and curcumin intervention model in vivo and vitro. RNA interference and overexpression technology, dual luciferase reporter gene detection, western blot etc. were used to identify the role of LncRNA769044-miR1679-STAT1 network and clarify the network in molecular mechanism of curcumin alleviating AFB1 hepatocytes necroptosis and inflammation in chicken which will provide new ideas and theoretical basis for the effective prevention and treatment of AFB1 liver injury and the discovery of new targets.