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  本文關鍵詞：豬慢性腦動靜脈畸形動物模型的建立　出處：《大連醫(yī)科大學》2007年碩士論文　論文類型：學位論文

  更多相關文章： 豬 腦動靜脈畸形 動物模型

【摘要】： 背景和目的:腦動靜脈畸形(arteriovenous malformation, AVM)為最常見的腦血管畸形,臨床表現(xiàn)為出血、頑固性頭痛、癲癇等;部分患者因長期腦內(nèi)盜血而進行性偏癱,嚴重威脅人們的生存質(zhì)量和生命安全。為了對腦動靜脈畸形(arteriovenous malformation, AVM)進行深入研究,人們陸續(xù)建立了多種腦AVM模型,無論是體外模型還是體內(nèi)無真性畸形團的動靜脈瘺模型,均存在著明顯不足。已有學者利用豬的顱底微血管網(wǎng)(rete mirabile, RM)作為畸形血管團制作腦AVM動物模型,其中以Massoud模型最為著名。但Massoud模型目前存在以下主要缺點:第一,模型的建立需要復雜的神經(jīng)介入技術和昂貴的介入材料(球囊、微彈簧圈、血管內(nèi)電凝等),操作費時,又大大增加了研究費用;第二,Massoud模型雖然首次具備了畸形血管團,但它遠不是我們臨床上常見的含有高流量動靜脈瘺的腦AVM;第三,頸動靜脈吻合口自發(fā)性血栓形成進而導致引流靜脈閉塞的機率很高;第四,Massoud模型的長期自然過程和動靜脈吻合口的長期通暢性尚不清楚,目前僅僅作為急性期模型。其他一些研究者在Massoud模型基礎上所建立的模型都因吻合口短期內(nèi)自發(fā)性閉塞而不能成為穩(wěn)定的動物模型,由于研究的樣本數(shù)量少而且未能進行對照研究,近期的相關研究未能獲得可靠的結論。因此,截至目前未能建立一個穩(wěn)定的模型對腦AVM進行系統(tǒng)研究。 本研究的目的,是在既往研究經(jīng)驗的基礎上,通過對吻合方法的改進建立模型,同時對不同吻合方式模型進行長期隨訪對照研究,以求建立一個既簡單經(jīng)濟,又長期穩(wěn)定,并與人腦AVM更加接近的腦AVM動物模型。 方法:利用13頭中國實驗用小型豬的顱底微血管網(wǎng)(RM)作為畸形團,分別采取兩種術式進行左側(cè)頸總動脈與頸外靜脈的吻合:端端吻合7例,作為觀察組;側(cè)側(cè)吻合6例,作為對照組;均外科結扎同側(cè)頸外動脈,同側(cè)咽升動脈肌支和枕動脈保持通暢。對兩組模型進行長期隨訪觀察,隨訪時間11-18個月(平均464.7天),考察兩組模型建立的難易程度,建模成功率,吻合口閉塞發(fā)生率以及模型的穩(wěn)定性,并從血管結構、造影影像上考察其與人腦AVM的可比擬性。 結果:13例動物中12例造模成功。頸外動脈直接外科結扎簡單、經(jīng)濟、可靠。結果表明,端端吻合操作更容易進行,以端端吻合建立的模型吻合血流速度更快。端端吻合造模成功率(100%)較側(cè)側(cè)吻合(83.33%)高,長期隨訪顯示端端吻合模型吻合口閉塞發(fā)生率(28.57%)較側(cè)側(cè)吻合(66.7%)低。端端吻合腦AVM動物模型R-APA直徑隨時間的延長而增加(P0.05);而側(cè)側(cè)吻合的腦AVM動物模型各指標前后無差異(P0.05);全部模型隨訪結束時RM體積、R-APA直徑較隨訪開始有顯著增加(P0.05),L-APA直徑亦有增加趨勢(P=0.065)。造影結果表明,右側(cè)頸外動脈通過吻合支RA、AA向RM供血,同時模型成功建立后,立即在左側(cè)椎動脈與左咽升動脈(通過左咽升動脈降支)及左頸總動脈(通過左枕動脈降支)之間自發(fā)形成動脈-動脈吻合,即假性動靜脈瘺(pAVF),因此,成功模型不僅含有多支供血動脈,而且為既含有叢狀形AVM又含有動靜脈瘺的“二合一”模型。 結論:通過比較研究,找到了一個建立更為理想的慢性豬腦AVM動物模型的方法,即通過一側(cè)頸動靜脈端端吻合和頸外動脈直接外科結扎,完全能夠建立一個簡單、經(jīng)濟、穩(wěn)定、高流量、更加接近臨床的慢性豬腦AVM模型。
[Abstract]:Background and objective: cerebral arteriovenous malformation (arteriovenous malformation AVM) is the most common cerebral vascular malformation, the clinical manifestations of hemorrhage, intractable headache, epilepsy; some patients due to long-term intracerebral steal and hemiplegia, a serious threat to people's living quality and life safety. In order to cerebral arteriovenous malformations (arteriovenous malformation AVM) for further research, people have built a variety of brain AVM model, both the arteriovenous fistula model in vitro and in vivo models without true malformation, there are obvious deficiencies. Some scholars use pig mirabile (rete mirabile RM) as a vascular malformation of brain AVM the animal model, the Massoud model is the most famous. But the present Massoud model has the following disadvantages: first, to establish the model of complex neural interventional techniques and expensive intervention materials (balloon, micro spring Ring, endovascular electrocoagulation), operation time, and greatly increased the cost of research; second, although the Massoud model for the first time with the vascular malformation, but it is far from our common clinical high flow arteriovenous fistula in third, cerebral AVM; carotid arteriovenous anastomosis spontaneous thrombosis causing drainage the probability of venous occlusion is very high; fourth, the long-term natural process of the Massoud model and the long-term patency of venous anastomosis is unclear, at present only as a model of acute phase model. Some other researchers established on the basis of Massoud model in the short term because of anastomotic spontaneous occlusion and can not become a reliable animal model because the number of samples is small, and no comparison, recent related research did not obtain reliable conclusions. Therefore, so far failed to establish a stable model of the system research on brain AVM The.
The purpose of this study is based on previous research experience, the establishment of the model through the improvement of the method of anastomosis, the different anastomosis model for long-term follow-up study, in order to establish a simple, economical, stable, and more close to the animal model of brain AVM and AVM in human brain.
Methods: using 13 China experimental miniature pig mirabile (RM) as the malformation, anastomosis were taken two kinds of operation of the left common carotid artery and external jugular vein: end-to-end anastomosis in 7 cases, as the observation group; side to side anastomosis in 6 cases, as the control group were with surgical ligation; the lateral carotid artery, the ipsilateral muscular branch of ascending pharyngeal artery and occipital artery patency. Long term follow-up observation of two groups of model, the follow-up time was 11-18 months (average 464.7 days), on the degree of difficulty of establishing two sets of model, modeling the success rate of anastomotic occlusion rate and the stability of the model, and from vascular structure, imaging the brain and AVM can be compared.
Results: 13 cases in 12 cases of animal model was made successfully. The external carotid artery direct surgical ligation is simple, economic and reliable. The results show that the end-to-end anastomosis operation easier, to establish the model of end-to-end anastomosis anastomosis flow faster. End to end anastomosis model success rate (100%) compared with side to side anastomosis (83.33%) high, long termfollow up end to end anastomosis model of anastomotic occlusion rate (28.57%) compared with side to side anastomosis (66.7%). The low end to end anastomosis of cerebral R-APA animal model of AVM diameter increased with time (P0.05); the differences in each index before and after cerebral AVM animal model and side to side anastomosis without end (P0.05); all the models showed that the volume of RM, R-APA were significantly increased in diameter than the diameter (P0.05), L-APA also has an increasing trend (P=0.065). The contrast results show that the right external carotid artery anastomosis by RA, AA and RM to the blood supply model successfully established, immediately in the left vertebral artery and left ascending pharyngeal (artery through the left ascending pharyngeal artery descending) and left common carotid artery (the left occipital artery) between the spontaneous formation of artery anastomosis, namely pseudo arteriovenous fistula (pAVF), therefore, the successful model not only contains multiple feeding arteries, but also contains both plexiform AVM and with arteriovenous fistula the "two in one" model.
Conclusion: through the comparative study, find a more ideal animal model of chronic brain AVM method, namely through the jugular arteriovenous anastomosis and end ligation of external carotid artery surgery, can set up a simple, economical, stable, high flow, closer to the chronic brain AVM model in clinical practice.

【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R-332

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