天然提取物大麻二酚通过PGE2-EP2-cAMP通路调控星形胶质细胞治疗创伤性脑水肿的机制研究

中重度脑创伤常伴有危及生命的创伤性脑水肿(TCE)，主要病理基础是破坏了血脑屏障(BBB)的结构和渗透性，其中星形胶质细胞是BBB的关键结构。我们先前证实脑创伤的病理变化与前列腺素系统、PGE2-EP2-cAMP信号通路活化密切相关，近期探索性发现天然提取物大麻二酚(CBD)能减轻星形胶质细胞足板肿胀，改善BBB通透性。然而CBD究竟对TCE的治疗效果如何及其作用机制等都尚不清楚。基于此，我们提出CBD可能通过PGE2-EP2-cAMP信号通路影响前列腺素代谢和调控星形胶质细胞活性而达到治疗TCE。本课题将从形态学、分子生物学、细胞学水平探究：①CBD对星形胶质细胞活性的调节；②CBD与前列腺素系统的相关性；③CBD的作用机制是否涉及PGE2-EP2-cAMP信号通路？期望在阐明CBD治疗脑创伤方面有新发现，为开展相关领域药物研究、探索天然药物价值提供可靠的形态学和分子生物学实验依据。

Moderate to severe traumatic brain injury (TBI) is often accompanied by life-threatening traumatic cerebral edema (TCE). A hallmark pathological feature of TBI is the destruction of blood-brain barrier (BBB) along with change of permeability. It is well documented that astrocytes play a key role in maintaining the structural and functional integrity of BBB. Our previous research found that the pathological changes in brain injury are closely related to the prostaglandin metabolism and activation of the PGE2-EP2-cAMP signaling pathway. Recently, we have found that Cannabidiol (CBD), a natural compound, can reduce the swelling or hypertrophy of astrocytic end-feet associated with the blood vessels and improve the BBB permeability; however, the therapeutic effect and its underlying mechanism on TCE have remained obscure. In light of the above, it was surmised that CBD might affect prostaglandin metabolism and regulate the astrocyte activation via the PGE2-EP2-cAMP signaling pathway to achieving its treatment effect of TCE. Therefore, by using experimental morphology, molecular biology and cytology techniques, this study aims to explore the following issues: ① The regulation of astrocyte activation by CBD; ② The correlation between CBD and prostaglandin metabolism; ③ To decipher the underlying mechanism of CBD in regulating the PGE2-EP2-cAMP signaling pathway. It is hoped that there will be new findings emerged from this study in the treatment of brain trauma by CBD, which would provide a reliable morphological and molecular basis for the research of related drugs and the embodiment of the value of natural drugs.