氨诱发星形胶质细胞水肿是肝性脑病的发病基础，但氨致细胞水肿机制不明。我们前期证实Na/K-ATP酶/哇巴因介导的表皮生长因子受体（EGFR）转激活在氨致星形胶质细胞水肿中具有重要作用。Ca2+-磷脂依赖性蛋白激酶通路是EGFR下游跨膜信号转导途径。我们预实验证实抑制该通路可显著缓解氨诱导的星形胶质细胞水肿。因此，我们推测Ca2+-磷脂依赖性蛋白激酶通路可能通过与Na/K-ATP酶/哇巴因-EGFR相互作用介导氨诱导的星形胶质细胞水肿。本研究拟利用原代培养的星形胶质细胞及荧光标记星形胶质细胞转基因小鼠，从体内体外两个水平研究Ca2+-磷脂依赖性蛋白激酶通路在氨致星形胶质细胞水肿的作用，其与Na/K-ATP酶/哇巴因-EGFR通路活化间的关系及其与MAPK/ERK通路间的交互作用关系。该项目将进一步阐明肝性脑病的发病机理，并有望为临床上该症的治疗提供新的、有针对性的靶点。

Ammonia-induced astrocyte swelling plays a major role in the pathogenesis of hepatic encephalopathy (HE). However, mechanisms by which ammonia exerts its neurotoxicity still remain poorly understood. We previously reported that Na/K-ATPase mediated epidermal growth factor receptor (EGFR) transactivation plays an important role in ammonia induced astrocyte swelling. Ca2+-phosphotide dependent protein kinase cascade is a transmembrane signal transduction pathway downstream of EGFR. Our preliminary results showed that inhibition of this pathway significantly alleviated ammonia induced astrocyte swellig. Based on this, we throw the hypothesis that Ca2+-phosphotide dependent protein kinase is involved in ammonia induced astrocyte swelling through interaction with Na/K-ATPase-EGFR signaling. This project amis to explore, both in vitro (using astrocyte cultures) and in vivo (using trangenic mice with fluorescence labeled astrocytes), the role of Ca2+-phosphotide dependent protein kinase pathway in ammonia induced astrocyte swelling, its relationship with Na/K-ATPase-EGFR signaling and the crosstalk between this pathway with MEK/ERK signaling. This project would further clarify the undyling mechanism of ammonia induced astrocytic sweling and thus promises to provide novel and specific target for HE therapy.