同步辐射脑血管造影在啮齿类动物卒中模型中的应用

发布时间：2018-04-16 07:41

本文选题：侧枝循环 + 卒中　；参考：《上海交通大学》2015年博士论文

【摘要】：卒中在我国是一种高发病率、高致死率、高致残率的严重疾病。啮齿类动物的线栓法大脑中动脉阻塞(MCAO)模型是普遍用于研究卒中的小动物模型,然而该模型存在诸多影响模型的稳定性和动物存活率的因素。因此,应用影像学方法对啮齿类动物线栓法大脑中动脉阻塞模型前后的脑血管和脑血流进行原位活体成像将有助于机制机理的研究并提高模型稳定性。卒中后存在不同级别侧枝循环的开放,其开放程度与卒中预后相关,雷帕霉素在卒中后可能具有促进侧枝开放的作用,在本论文的研究中,我们应用和发展了基于X射线的活体同步辐射脑血管造影技术,并结合活体激光散斑成像和核磁共振成像、离体组织学染色等技术,研究了以下五部分内容并获得了相关结论:第一,线栓法大鼠大脑中动脉阻塞模型术后存在翼腭动脉到颌外动脉的侧枝循环,该颅外侧枝循环保证了咀嚼肌不受颈外动脉切断的影响;术中颈外动脉的切断不是导致术后体重下降的主要原因,证明了术后存在颅外大血管间的侧枝循环。第二,线栓法大鼠短暂性大脑中动脉阻塞模型术后存在眼动脉吻合支、颈内动脉和眼动脉间的侧枝循环、颈内动脉和翼腭动脉间的侧枝循环;大鼠永久性大脑中动脉阻塞后存在翼腭动脉和硬脑膜动脉间的侧枝循环,但不存在翼腭动脉和大脑中动脉间的侧枝循环,证明翼腭动脉的结扎并不能影响梗死体积的稳定性。第三,线栓法大鼠短暂性大脑中动脉阻塞模型术中由线栓引起的血管内血栓形成是影响线栓法小鼠短暂性大脑中动脉阻塞模型再灌注的关键影响因素,小剂量肝素干预能有效提高模型的再灌注成功率,从而提高模型的稳定性。第四,我们发展了一种基于造影剂密度时空变换拟合分析的功能性同步辐射脑血管造影(fSRA)技术(完整源代码见附录);应用该技术,发现大鼠短暂性大脑中动脉阻塞后的豆纹动脉的血管弹性在缺血后1天至7天逐渐降低,从7天至28天逐渐恢复,此变化与水肿体积的变化正相关,但与血流速度的变化负相关。该结果证明脑缺血后血管弹性的变化可能与脑水肿和血流速度有关。第五,雷帕霉素干预能维持小鼠短暂性大脑中动脉阻塞后脑表面软脑膜侧枝动脉的开放,增加其血流速度,并扩张大脑后动脉和大脑中动脉间侧枝动脉的直径,进而增加大鼠血栓性大脑中动脉阻塞后大脑中动脉区域的血液灌注。该结果证明了雷帕霉素能通过促进颅内侧枝循环的开放而起到脑保护的作用。以上研究结果将有助于推动同步辐射脑血管造影技术的发展,并使之更广泛地应用于卒中的基础研究和临床应用。
[Abstract]:Stroke is a serious disease with high morbidity, high mortality and high disability rate in China.The middle cerebral artery occlusion (MCAO) model of rodents is widely used to study the small animal model of stroke. However, there are many factors that influence the stability and survival rate of the model.Therefore, in situ imaging of cerebral vessels and cerebral blood flow before and after middle cerebral artery occlusion in rodents will be helpful to study the mechanism and improve the stability of the model.There are different levels of collateral circulation opening after stroke, and the degree of opening is related to the prognosis of stroke. Rapamycin may play a role in promoting collateral opening after stroke.We have applied and developed in vivo synchrotron radiation cerebrovascular angiography based on X ray, combined with in vivo laser speckle imaging and nuclear magnetic resonance imaging, in vitro histological staining, and so on.The following five parts were studied and the relevant conclusions were obtained: first, there was collateral circulation from pterygopalatine artery to external maxillary artery after middle cerebral artery occlusion in rats.The lateral branch circulation ensures that the masticatory muscle is not affected by the external carotid artery transection, and the external carotid artery transection is not the main cause of weight loss after operation, which proves the existence of lateral branch circulation between the extracranial great vessels after operation.Second, there were anastomotic branches of ophthalmic artery, collateral circulation between internal carotid artery and ophthalmic artery, and collateral circulation between internal carotid artery and pterygopalatine artery.There was collateral circulation between pterygopalatine artery and dural artery after permanent middle cerebral artery occlusion in rats, but there was no collateral circulation between pterygopalatine artery and middle cerebral artery, which proved that ligation of pterygopalatine artery could not affect the stability of infarct volume.Third, intravascular thrombosis induced by thread embolus was the key factor affecting reperfusion of transient middle cerebral artery occlusion model in rats.Small dose heparin intervention can effectively improve the reperfusion success rate of the model, thereby improving the stability of the model.Fourth, we developed a functional synchrotron radiation angiography (fSRAs) technique based on spatio-temporal transformation fitting analysis of contrast medium density (see appendix for the complete source code).It was found that the vascular elasticity of the lenticular artery after transient middle cerebral artery occlusion decreased gradually from 1 to 7 days after ischemia, and recovered gradually from 7 to 28 days after ischemia. This change was positively correlated with the change of edema volume.However, there was a negative correlation between blood flow velocity and blood flow velocity.The results suggest that the changes of vascular elasticity after cerebral ischemia may be related to cerebral edema and blood flow velocity.Fifth, rapamycin intervention can maintain the opening of the superficial pial collateral artery after transient middle cerebral artery occlusion in mice, increase its blood flow velocity, and dilate the diameter of the posterior cerebral artery and the intercerebral artery between the middle cerebral artery and the posterior cerebral artery.And then increase the blood perfusion in the middle cerebral artery area after thrombotic middle cerebral artery occlusion in rats.The results suggest that rapamycin can protect the brain by promoting the opening of intracranial collateral circulation.The above results will help to promote the development of synchrotron radiation cerebrovascular angiography technology and make it more widely used in the basic research and clinical application of stroke.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R743.3;R-332

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