肾集合管泌钾对维持钾代谢稳态、调节细胞内外的渗透压平衡和机体新陈代谢至关重要。雷帕霉素靶蛋白复合物2 (mTORC2)是调节细胞代谢与细胞存活等生理活动的关键分子，但mTORC2在集合管泌钾中的作用及其上、下游调控机制不清楚。我们在前期工作中使用药物抑制mTORC2活性后，小鼠出现泌钾障碍，且血清醛固酮水平显著升高；集合管特异敲除Rictor(mTORC2关键组份)的小鼠在高钾饮食时血钾比野生型显著增加。本课题拟以集合管特异敲除Rictor，以及mTORC2抑制剂处理的小鼠和细胞为模型，探讨集合管细胞mTORC2活性受机体血钾水平与醛固酮调节的上游机制，以及集合管细胞mTORC2活性改变后调节钾分泌的下游机制，从分子、细胞与整体水平阐明集合管细胞mTORC2在肾脏钾分泌和维持钾代谢稳态中的作用及其调节机理，为肾脏钾代谢调节与mTOR功能提供新内容，钾代谢稳态失衡相关疾病的防治提供新思路。

Potassium secretion in kidney collecting duct is important for the maintenance of potassium homeostasis, cellular osmotic pressure balance and body metabolism. The mechanistic target of rapamycin complex 2 (mTORC2) plays key roles in the regulation of cell metabolism and survival, while its roles in the regulation of collecting duct potassium secretion and the upstream and downstream signaling are not clear. We previously found that inhibition of mTORC2 activity in vivo caused potassium secretion dysfunction and increased the serum aldosterone level. Then we generated the mice with collection duct specific deletion of Rictor (a key member of mTORC2),and found that the mice exhibited urinary potassium secretion disorder in high potassium diet condition. In this study, by using the Rictor conditional knockout mice and cells, combined with the animal model treated with mTORC2 inhibitor, we aim to investigate the roles of mTORC2 in the potassium secretion in collecting duct and the maintenance of metabolic homeostasis, providing experimental basis and theoretical support for the prevention and treatment of potasium secretion related diseases.