猪慢性脑动静脉畸形动物模型的建立

发布时间：2018-01-11 22:17

本文关键词：猪慢性脑动静脉畸形动物模型的建立　出处：《大连医科大学》2007年硕士论文　论文类型：学位论文

【摘要】： 背景和目的:脑动静脉畸形(arteriovenous malformation, AVM)为最常见的脑血管畸形,临床表现为出血、顽固性头痛、癫痫等;部分患者因长期脑内盗血而进行性偏瘫,严重威胁人们的生存质量和生命安全。为了对脑动静脉畸形(arteriovenous malformation, AVM)进行深入研究,人们陆续建立了多种脑AVM模型,无论是体外模型还是体内无真性畸形团的动静脉瘘模型,均存在着明显不足。已有学者利用猪的颅底微血管网(rete mirabile, RM)作为畸形血管团制作脑AVM动物模型,其中以Massoud模型最为著名。但Massoud模型目前存在以下主要缺点:第一,模型的建立需要复杂的神经介入技术和昂贵的介入材料(球囊、微弹簧圈、血管内电凝等),操作费时,又大大增加了研究费用;第二,Massoud模型虽然首次具备了畸形血管团,但它远不是我们临床上常见的含有高流量动静脉瘘的脑AVM;第三,颈动静脉吻合口自发性血栓形成进而导致引流静脉闭塞的机率很高;第四,Massoud模型的长期自然过程和动静脉吻合口的长期通畅性尚不清楚,目前仅仅作为急性期模型。其他一些研究者在Massoud模型基础上所建立的模型都因吻合口短期内自发性闭塞而不能成为稳定的动物模型,由于研究的样本数量少而且未能进行对照研究,近期的相关研究未能获得可靠的结论。因此,截至目前未能建立一个稳定的模型对脑AVM进行系统研究。本研究的目的,是在既往研究经验的基础上,通过对吻合方法的改进建立模型,同时对不同吻合方式模型进行长期随访对照研究,以求建立一个既简单经济,又长期稳定,并与人脑AVM更加接近的脑AVM动物模型。方法:利用13头中国实验用小型猪的颅底微血管网(RM)作为畸形团,分别采取两种术式进行左侧颈总动脉与颈外静脉的吻合:端端吻合7例,作为观察组;侧侧吻合6例,作为对照组;均外科结扎同侧颈外动脉,同侧咽升动脉肌支和枕动脉保持通畅。对两组模型进行长期随访观察,随访时间11-18个月(平均464.7天),考察两组模型建立的难易程度,建模成功率,吻合口闭塞发生率以及模型的稳定性,并从血管结构、造影影像上考察其与人脑AVM的可比拟性。结果:13例动物中12例造模成功。颈外动脉直接外科结扎简单、经济、可靠。结果表明,端端吻合操作更容易进行,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%)较侧侧吻合(83.33%)高,长期随访显示端端吻合模型吻合口闭塞发生率(28.57%)较侧侧吻合(66.7%)低。端端吻合脑AVM动物模型R-APA直径随时间的延长而增加(P0.05);而侧侧吻合的脑AVM动物模型各指标前后无差异(P0.05);全部模型随访结束时RM体积、R-APA直径较随访开始有显著增加(P0.05),L-APA直径亦有增加趋势(P=0.065)。造影结果表明,右侧颈外动脉通过吻合支RA、AA向RM供血,同时模型成功建立后,立即在左侧椎动脉与左咽升动脉(通过左咽升动脉降支)及左颈总动脉(通过左枕动脉降支)之间自发形成动脉-动脉吻合,即假性动静脉瘘(pAVF),因此,成功模型不仅含有多支供血动脉,而且为既含有丛状形AVM又含有动静脉瘘的“二合一”模型。结论:通过比较研究,找到了一个建立更为理想的慢性猪脑AVM动物模型的方法,即通过一侧颈动静脉端端吻合和颈外动脉直接外科结扎,完全能够建立一个简单、经济、稳定、高流量、更加接近临床的慢性猪脑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.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R-332

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