基于功能磁共振探索中药注射液早期干预缺血性脑梗死脑网络的疗效机制研究

Early intervention with chinese medicine can not only minimize the treatment delay of pre-hospital and in-hospital, but also extend benefits to people. As the treatment of ischemic cerebral infarction limited, traditional chinese medicine injection could improve the recovery of nervous function according to chinese medicine theory. Functional magnetic resonance imaging is a mature and reliable image inspection method, that not only reflects brain function objectively and accurately, but also can be used to study the efficacy of the mechanism. Based on this, this proposal raises the following scientific hypothesis "traditional chinese medicine injection can be used as a early treatment for ischemic cerebral infarction via promoting nervous function reconstruction by connecting the brain structure and function networks". To test this hypothesis, we will perform a longitudinal study with traditional chinese medicine injection early intervention by combining randomized controlled clinical trials and imaging technology based on functional magnetic resonance imaging. The patients of ischemic cerebral infarction within 12 hours onset will be observed for clinical and functional imaging evaluations. By this study, we can not only improve the clinical efficacy treating acute ischemic cerebral infarction, but also explore the therapeutic mechanism of early intervention with traditional chinese medicine injection. Imaging evidence with chinese medicine treatment could be provided and the acceptability of chinese medicine internationally could be increased by our study.

中医药早期干预脑梗死可最大限度地减少院前和院内救治延迟，扩大受益人群。因脑梗死早期干预治疗手段有限，中药注射液能够促进早期神经功能重塑。功能磁共振成像是较为成熟可靠的检查手段，不仅可以客观、精确地反应大脑功能，还可以用于疗效机制研究。基于此，本课题提出“中药注射液可以改变脑结构连接网络和功能连接网络促进神经功能重塑早期治疗缺血性脑梗死”的科学假说。为验证假说，我们将基于功能磁共振，以中药注射液为早期干预手段，以发病12小时以内的缺血性脑梗死患者为研究对象，开展随机对照临床试验与影像相结合的纵向研究，进行动态、多时点地临床疗效和功能影像学评估。通过本课题的研究，不仅可以提高急性缺血性脑梗死的临床疗效，还能探索中药注射液药物作用的疗效机制，提供中医药治疗的影像学证据，提高中医药在国际上的接受度。

缺血性脑梗死是临床最常见的卒中类型，具有高致残率和高复发率。中医学认为，血瘀证是缺血性中风的核心病机，贯穿疾病始终。在发病早期使用中药注射液在促进神经功能恢复、改善预后方面有显著优势。基于以上中医病机，本项目完成了104例急性缺血性脑梗死患者的动态随机对照临床评估，其中20例干预组、18例对照组完成多时点功能磁共振试验，另有20例健康被试完成功能磁共振试验。本项目证实中药注射液治疗缺血性脑梗死急性期的临床疗效，神经功能缺损、病残程度、日常生活能力均显著改善，并发现中药注射液对神经功能的改善主要表现在远期疗效，即发病90天后，短期疗效不显著，即发病14天和28天无显著优势。本项目探索了缺血性脑梗死可能的脑网络发病机制及中药注射液治疗的脑网络疗效机制。缺血性脑梗死发病72小时内存在广泛的神经元活动和脑功能网络连接异常，右侧楔叶和左侧额中回神经元活动显著降低，而中药注射液治疗3个月后逐渐恢复至正常水平。虽然异常的网络内和网络间功能连接经治疗后1个月、3个月均得到不同程度的恢复，然而各自呈现不同的恢复机制，视觉网络内右侧楔叶功能连接显著降低，治疗后3个月恢复正常；而默认网络内右侧楔前叶功能连接显著降低，治疗后1个月恢复正常；左侧额顶叶网络与突显网络间的功能连接代偿性增强，治疗后1个月恢复正常。这种异常的功能网络内和网络间连接的改善对神经功能的恢复起到关键作用，由此临床早期康复训练重视差异网络的刺激训练可改善中风后的神经功能康复，从而提高临床疗效。以上结论可以为中药注射液早期干预缺血性脑梗死的应用提供客观的可视化影像学证据，探索基于中药注射液疗效基础上的疗效观察试验研究模式。