天麻素通过外泌体途径调控miR-20a-5p/XIAP通路抑制脑梗死急性期神经元凋亡的机制研究

熄风法是脑梗死急性期关键治法，早期熄风对提高临床疗效具有重要意义。天麻为平肝熄风代表药物，而天麻素是其中含量最高的有效单体。研究报道天麻素在脑梗死急性期治疗中发挥良好疗效，前期研究提示天麻素可保护MCAO大鼠神经功能，并抑制神经元凋亡，但是难以透过血脑屏障是解析其作用机制的关键瓶颈。外泌体可穿越血脑屏障、介导细胞间通讯，预实验发现天麻素可以升高循环外泌体中miR-20a-5p的含量，而XIAP为miR-20a-5p的靶标，可多途径调控细胞凋亡。据此提出研究假说：天麻素可能通过外泌体调控miR-20a-5p/XIAP信号通路抑制脑梗死后神经元凋亡。本研究利用脑梗死动物及细胞模型，通过外泌体示踪标记、荧光原位杂交、基因沉默等关键技术，拟从外泌体角度揭示天麻素抑制神经元凋亡的新机制，为其应用于脑梗死急性期提供实验支持；并为探索中药成分如何突破血脑屏障的阻碍有效治疗脑梗死这一研究难题开拓新思路。

Extinguish Wind method in early stage of cerebral infarction is crucial in clinical treatment. Gastrodin (Gas) is the most enriched ingredient in gastrodia elata, which is representative TCM medicine in Extinguish Wind. Clinical data shows a promising effect of Gas in treatment of acute stroke. In addition, our previous research proved Gas had protective effect on neurological function of MCAO rats, also could inhibit apoptosis of neuron. As we know, Gas can’t penetrate BBB, so how can Gas take effect is the key point in studying mechanism. Exosome is generally noticed in recent years due to its multifunction such as penetration of BBB, conduction signal between cells. Our pre-experiment revealed Gas could increase amount of miR-20a-5p in circulating exosome, and XIAP, a multiple regulator of apoptosis, is the target of it. So we develop our working hypothesis, Gas can inhibit neuronal apoptosis in acute stage of cerebral infarction through regulating miR-20a-5p/XIAP pathway by exosome. This research aims at exploring mechanism of protective effect of Gas on neuron in vitro and vivo. Many approaches are used including exosome tracer tag, FISH, gene silencing, etc. We intend to offer experimental support of Gas for applying in acute stroke, as well as discover novel idea on how TCM ingredient can break through BBB and take effect in acute stroke.