颅内动脉粥样硬化性狭窄性疾病中脑血管新生作用研究

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of reccurrent stroke in China. There is a significant unmet need for new methods to manage Chinese patients with Intracranial atherosclerotic stenosis. Ischemic stroke and cerebral hypoperfusion can induce endogenous angiogenesis, which is associated with improved functional outcome. There are lots of strategies sprang up targeting on angiogenesis. However，little was known about angiogenesis in patients with ICAS. In the previous study of our team, we have found that there is angiogenesis in corresponding cerebral areas of involved artery in patients with symptomatic ICAS. Therefore, we proposed that ICAS induce endogenous angiogenesis, which was correlated with prognosis of ICAS. We plan to observe if there is angiogenesis in such patients through imaging of brain, serum biomarkers and cytology of angiogenesis by 68Ga-BNOTA-PRGD2 PET image, protein biochip array, ELISA and flow cytometry. Furthermore, we will discuss the correlation between angiogenesis and prognosis, as well as the mechanism of angiogenesis in patients with ICAS. This project is an original research into angiogenesis in patients with ICAS, which was important in illuminating mechanisms of angiogenesis in ICAS, as well as providing theoretical basis of targeting angiogenesis as a new strategy for ICAS management.

颅内动脉粥样硬化性狭窄（ICAS）是引起中国人群复发性脑卒中的重要原因，尚缺乏有效的治疗手段。血管新生是目前治疗脑缺血性疾病的研究热点。但是目前关于血管新生在ICAS患者中的表达情况与作用尚不明确。我们在前期研究中发现症状性ICAS患者在狭窄动脉供血区存在脑血管新生。因此，我们推测在ICAS患者中存在内源性脑血管新生，且这种血管新生与ICAS患者预后相关。为证实这一假说，我们通过68Ga-BNOTA-PRGD2 PET血管新生成像技术，蛋白质芯片和ELISA法、流式细胞术，从影像学-血液生化学-细胞学三方面，观察ICAS患者中内源性血管新生的情况，探讨其与预后的相关性，研究ICAS患者内源性血管新生的分子和细胞学机制。本课题在国内外首次对ICAS患者脑内血管新生的情况直接进行影像学评估，对阐明ICAS内源性血管新生的机制有重要意义，同时也为血管新生作为ICAS的治疗靶点提供理论依据。

颅内大动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis, ICAS）是缺血性脑卒中的重要病因，患者有较高的缺血性脑卒中发病率与复发率。血管新生在评估ICAS患者的病情进展、预后具有重要意义。本课题运用分子影像技术及血清生物学标记物对颅内动脉粥样硬化狭窄性疾病中血管新生进行分析，探讨ICAS患者中血管新生的机制及可能的影响因素，为ICAS患者的病情监测、疗效监测提供新方法，为ICAS患者提供新的治疗方向。课题运用68Ga-BNOTA-PRGD2 PET/CT 技术（RGD标记整合素αvβ3）观察ICAS患者不同时期脑血管新生情况，同时探讨血管新生因子及炎性因子在ICAS患者血管新生发生过程中的作用及机制。课题组在国内外首次运用分子影像技术证实ICAS患者中血管新生情况，重度颅内动脉粥样硬化性狭窄/闭塞患者存在脑血管新生，不同时程脑血管新生存在一定的差异，血管新生与脑血流灌注呈负相关，血管新生因子VEGF、PDGF-BB及整合素αvβ3水平均显著升高，炎症因子IL-6、IGF-1、VCAM-1在有脑血管事件史的重度颅内动脉粥样硬化性狭窄或闭塞患者血清中水平明显高于健康人群，其中IL-6可能与脑卒中复发风险相关。课题结论对研究探索颅内大动脉粥样硬化狭窄患者血管新生发生机制、监测评估脑侧支循环及治疗靶点方面具有重要的学术价值。研究成果发表于国际高水平专业期刊《JCFBM》（IF:6.081）,并在国际学术会议交流。已培养博士研究生2名。