芳香开窍法是中医治疗急性缺血性脑中风(AIS)的重要治则，在恢复脑功能方面有显著疗效，但具体作用机制不详。我们研究证实，脂肪酸代谢物异常变化是AIS模型代谢物组的显著特征；芳香开窍法干预后，能使异常变化的脂肪酸代谢物组全面回调，提示其可能的作用机制是通过影响脂肪酸代谢而发挥"开窍醒神"的作用。细胞因子脂联素、Angptl3、RBP4被发现与脂肪酸代谢有密切关系；同时AMPK是影响脂肪酸代谢平衡的重要靶点。基于代谢物组、脂代谢细胞因子和AMPK-ACC-CPT信号通路揭示芳香开窍法干预AIS脂肪酸代谢的根本原因应该是非常可行的。我们首次采用MCAO模型大鼠和HepG2细胞模型，利用代谢组学和分子生物学技术，从整体-细胞-分子水平观察芳香开窍法对AMPK活化、脂代谢细胞因子活性和脂肪酸代谢物组的影响，明确其是否通过调控AMPK-ACC-CPT而调节AIS中游离脂肪酸代谢发挥"开窍醒神"作用。

Treatment of opening the orifices with aroma is one of the most important principles of treating acute ischemic stroke (AIS) which has significant neuroprotective effect on restoring brain function, but its specific mechanism of such pharmacological action is still unknown. Our researches has proved that the abnormal variations of the metabolism of fatty acids is the distinguishing feature of metabolites group in AIS model, while the metabolites of the fatty acids tended to the normal level after intervening with resuscitation-inducing therapy with fragrant drugs. It is revealed that the possible mechanism of this therapy with "inducing resuscitation" is to maintain the balance of endogenous metabolites through affecting the metabolism of fatty acids. Adiponectin, Angptl3, and RBP4 are the most important cytokines which were proved having close connection with metabolism of fatty acids, and AMPK is also one of the important target spots affecting the balance of fatty acid metabolism. It is feasible to disclose the fundamental cause of treatment of opening the orifices with aroma affecting lipid metabolism of AIS based on metabolites, cell factors of lipid metabolism and AMPK-ACC-CPT signaling pathway. We firstly applied MCAO model and HepG2 cell model to study the effect of treatment of opening the orifices with aroma on AMPK activation, lipid metabolism cell factor activity and metabolites of fatty acids at the entirety-cell-molecular level by using metabolism and molecular biology technology, we are trying to confirm the therapy has the function of inducing resuscitation by adjusting the metabolism of free fatty acids through regulating AMPK-ACC-CPT.

前期研究发现芳香开窍法对于急性缺血性卒中具有良好效果，苏合香丸和安宫牛黄丸为芳香开窍法代表方剂，在临床上治疗中风已有数百年的应用历史,但具体作用机制不明确。本采用大鼠局灶性脑缺血（MCAO）模型模拟人缺血性卒，，给予安宫牛黄丸和苏合香丸干预。根据神经行为学评分、TTC染色、werstern-blot技术检测大鼠脑组织凋亡相关蛋白及AMPK的表达，探讨芳香开窍法治疗缺血性卒中的可能机制。研究结果显示：假手术组神经行为学评分在0~1分之间，未见偏瘫、追尾。模型组在2~4分之间，随时间推移，偏瘫、追尾等症状越来越重。安宫牛黄丸、苏合香丸高剂量组术后2h神经行为学评分在2~3分之间，但随时间推移，偏瘫、追尾症状有所缓解，在第24h缓解更明显。TTC染色结果显示假手术组TTC染色未见梗死灶，全脑呈均匀红色，其他各组均可见右侧大脑半球外侧面苍白色梗死灶。模型组与除苏合香丸低剂量组外，脑梗死体积差异均有统计学意义（p值均<0.01）。给药组高剂量与低剂量间，差异暂不具有统计学意义。与模型组比较，安宫牛黄丸组、苏合香丸组显著下调促凋亡因子Bax、caspase-3含量（P<0.05），显著上调抗凋亡因子Bcl-2含量增高（P<0.05），Bcl-2/Bax比值显著增高（P<0.05）。与模型组比较，安宫牛黄丸组、苏合香丸组显著降低AMPK含量（P<0.05）。安宫牛黄丸、苏合香丸可通过减少促神经凋亡因子Bax、caspase-3的表达、增高抑制神经凋亡因子Bcl-2的表达来减轻急性缺血性中风后神经元凋亡。安宫牛黄丸、苏合香丸可下调AMPK的表达，在急性缺血性中风后发挥神经保护作用。