發(fā)布時(shí)間：2018-04-16 07:41

  本文選題：側(cè)枝循環(huán) + 卒中��； 參考：《上海交通大學(xué)》2015年博士論文

【摘要】：卒中在我國(guó)是一種高發(fā)病率、高致死率、高致殘率的嚴(yán)重疾病。嚙齒類(lèi)動(dòng)物的線栓法大腦中動(dòng)脈阻塞(MCAO)模型是普遍用于研究卒中的小動(dòng)物模型,然而該模型存在諸多影響模型的穩(wěn)定性和動(dòng)物存活率的因素。因此,應(yīng)用影像學(xué)方法對(duì)嚙齒類(lèi)動(dòng)物線栓法大腦中動(dòng)脈阻塞模型前后的腦血管和腦血流進(jìn)行原位活體成像將有助于機(jī)制機(jī)理的研究并提高模型穩(wěn)定性。卒中后存在不同級(jí)別側(cè)枝循環(huán)的開(kāi)放,其開(kāi)放程度與卒中預(yù)后相關(guān),雷帕霉素在卒中后可能具有促進(jìn)側(cè)枝開(kāi)放的作用,在本論文的研究中,我們應(yīng)用和發(fā)展了基于X射線的活體同步輻射腦血管造影技術(shù),并結(jié)合活體激光散斑成像和核磁共振成像、離體組織學(xué)染色等技術(shù),研究了以下五部分內(nèi)容并獲得了相關(guān)結(jié)論:第一,線栓法大鼠大腦中動(dòng)脈阻塞模型術(shù)后存在翼腭動(dòng)脈到頜外動(dòng)脈的側(cè)枝循環(huán),該顱外側(cè)枝循環(huán)保證了咀嚼肌不受頸外動(dòng)脈切斷的影響;術(shù)中頸外動(dòng)脈的切斷不是導(dǎo)致術(shù)后體重下降的主要原因,證明了術(shù)后存在顱外大血管間的側(cè)枝循環(huán)。第二,線栓法大鼠短暫性大腦中動(dòng)脈阻塞模型術(shù)后存在眼動(dòng)脈吻合支、頸內(nèi)動(dòng)脈和眼動(dòng)脈間的側(cè)枝循環(huán)、頸內(nèi)動(dòng)脈和翼腭動(dòng)脈間的側(cè)枝循環(huán);大鼠永久性大腦中動(dòng)脈阻塞后存在翼腭動(dòng)脈和硬腦膜動(dòng)脈間的側(cè)枝循環(huán),但不存在翼腭動(dòng)脈和大腦中動(dòng)脈間的側(cè)枝循環(huán),證明翼腭動(dòng)脈的結(jié)扎并不能影響梗死體積的穩(wěn)定性。第三,線栓法大鼠短暫性大腦中動(dòng)脈阻塞模型術(shù)中由線栓引起的血管內(nèi)血栓形成是影響線栓法小鼠短暫性大腦中動(dòng)脈阻塞模型再灌注的關(guān)鍵影響因素,小劑量肝素干預(yù)能有效提高模型的再灌注成功率,從而提高模型的穩(wěn)定性。第四,我們發(fā)展了一種基于造影劑密度時(shí)空變換擬合分析的功能性同步輻射腦血管造影(fSRA)技術(shù)(完整源代碼見(jiàn)附錄);應(yīng)用該技術(shù),發(fā)現(xiàn)大鼠短暫性大腦中動(dòng)脈阻塞后的豆紋動(dòng)脈的血管彈性在缺血后1天至7天逐漸降低,從7天至28天逐漸恢復(fù),此變化與水腫體積的變化正相關(guān),但與血流速度的變化負(fù)相關(guān)。該結(jié)果證明腦缺血后血管彈性的變化可能與腦水腫和血流速度有關(guān)。第五,雷帕霉素干預(yù)能維持小鼠短暫性大腦中動(dòng)脈阻塞后腦表面軟腦膜側(cè)枝動(dòng)脈的開(kāi)放,增加其血流速度,并擴(kuò)張大腦后動(dòng)脈和大腦中動(dòng)脈間側(cè)枝動(dòng)脈的直徑,進(jìn)而增加大鼠血栓性大腦中動(dòng)脈阻塞后大腦中動(dòng)脈區(qū)域的血液灌注。該結(jié)果證明了雷帕霉素能通過(guò)促進(jìn)顱內(nèi)側(cè)枝循環(huán)的開(kāi)放而起到腦保護(hù)的作用。以上研究結(jié)果將有助于推動(dòng)同步輻射腦血管造影技術(shù)的發(fā)展,并使之更廣泛地應(yīng)用于卒中的基礎(chǔ)研究和臨床應(yīng)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.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R743.3;R-332

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