Abstract：
Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.
摘要：
缺血性卒中后脑水肿可加重静脉溶栓患者的脑损伤。山茱萸Sieb。等Zucc。,一种历史悠久的中药，有利于治疗包括缺血性中风在内的神经退行性疾病。特别是,它的主要组成部分，山茱萸环烯醚萜苷（CIG），被证明对脑缺血/再灌注损伤(CIR/I)表现出神经保护作用。目的探讨CIG对CIR/I大鼠脑水肿的影响,使用HPLC分析CIG与主要成分。在CIG成分和AQP4-M23之间进行分子对接分析。AQP4抑制剂TGN-020,用作比较。在体内实验中，用CIG预处理大鼠，并通过进行大脑中动脉闭塞/再灌注（MCAO/R）进行损伤。24小时后，对大鼠进行神经功能检查,病理变化,脑水肿,和极化的Aqp4在大脑中的表达。HPLC分析表明，CIG由莫诺苷和马钱素组成。分子对接分析表明，莫诺苷和马钱素对AQP4-M23的结合能均低于TGN-020。TheCIG预处理的大鼠表现出更少的神经功能缺损，最小化脑肿胀，与MCAO/R大鼠相比，病变体积减少。在梗死周围和梗死区域，CIG预处理恢复了在MCAO/R大鼠中丢失的极化Aqp4表达。结果表明，CIG可以通过AQP4-M23与莫诺苷和马钱素的相互作用调节极化的Aqp4来减轻脑缺血/再灌注大鼠的脑水肿。
