中文摘要
氧化应激机制是Tourette综合征(TS)的重要发病机制,先期研究表明TS存在氧化与还原失衡,静安口服液可降低自由基水平、提高抗氧化酶含量;蛋白组学研究筛选出差异蛋白Adrenodoxin(高表达),此蛋白参与NADPH在线粒体的氧化还原呼吸链反应。由此提出科学假说:神经细胞Adrenodoxin过表达激化了氧化应激反应,自由基等产物引发线粒体和DNA损伤、神经元凋亡、多巴胺等神经递质代谢紊乱,致TS发生;静安口服液通过调节Adrenodoxin而抑制氧化应激损伤、对抗抽动发生。将建立TS模型、培养神经细胞PC12并构建Adx过表达转染质粒,运用western blot、PCR、免疫组化及流式细胞术等方法检测NADPH及其催化酶、自由基、抗氧化酶的含量以及促存活信号通路蛋白表达水平,观察细胞受损及神经递质失衡情况。本研究将有助于阐明静安口服液抑制TS氧化应激损伤的科学内涵。
英文摘要
Oxidative stress is an important mechanism for the pathogenesis of Tourette syndrome (TS).Previous research indicated that imbalances of oxidation and reduction were involved in TS. Jing'an Oral liquid can reduce the level of free radical, and increase the level of antioxidant enzyme; Through proteomic we screened a protein Adrenodoxin which may participate in redox of NADPH. Based on these studies, we propose scientific hypothesis: In neurons, Adrenodoxin overexpression can induce oxidative stress; Products of oxidative stress, including ROS, lead to mitochondrial DNA damage,neuronal apoptosis, dopamine metabolic disorders, then cause the occurrence of TS; Jingan Oral liquid inhibit oxidative stress, prevent the occurrence of tics by regulating Adrenodoxin. We will detect the expression levels of NADPH、NOX、free radicals、antioxidant enzymes、pro-survival signaling pathways protein and observe the cell damage and neurotransmitter imbalances by establishing a TS model, culturing PC-12 cells model which transfect Adx plasmid, and using methods and techniques including proteomics, western blot, PCR, flow cytometry. This study will clarify the scientific connotation that Jing'an oral liquid inhibit oxidative stress injury in TS.
