兔耳透明质酸动脉栓塞模型的建立及透明质酸酶溶栓效果的评估

发布时间：2017-12-31 16:12

本文关键词：兔耳透明质酸动脉栓塞模型的建立及透明质酸酶溶栓效果的评估　出处：《北京协和医学院》2016年博士论文　论文类型：学位论文

【摘要】：一、研究目的1.掌握兔颈部和耳部血管解剖走行和分布情况,为建立兔耳岛状皮瓣和经颈外动脉选择性溶栓治疗奠定解剖学基础。2.制作兔耳岛状皮瓣,为建立以此为基础的透明质酸(hyaluronic acid, HA)动脉栓塞皮肤缺血模型奠定基础。3.建立兔耳岛状皮瓣HA动脉栓塞皮肤缺血模型,比较不同剂量HA动脉栓塞后皮瓣再灌注面积的差异,观察血管的病理学改变。4.验证血管内应用透明质酸酶(hyaluronidase, HAase)治疗HA动脉栓塞皮肤缺血性病变的效果,比较全身静脉溶栓和选择性动脉溶栓疗效的差异。二、研究方法1.实验白兔8只,通过化学性血管铸型的方法,制作头颈部血管铸型标本,观察颈部和耳部血管解剖情况。2.实验白兔5只,制作2.5×6cm、以耳廓后动脉及耳后静脉内侧支为蒂的岛状皮瓣。术后4h、24h、3天、5天和7天行荧光血管造影(fluorescein angiography,FA)检查,观察皮瓣灌注和成活情况。3.实验白兔18只,制作岛状皮瓣后,经耳廓后动脉注射HA,根据注射量不同分为10 μl、20 μ1和40 μl组。术后4h、24h、3天、5天和7天行FA检查,比较三组在相同时间点皮瓣灌注面积百分比的差异。观察各组术后24h和7天时血管病理改变。4.实验白兔20只,首先制作20μlHA动脉栓塞皮肤缺血模型,根据治疗方式不同分为4组：生理盐水全身静脉溶栓对照组(IVT-NaCl组)、HAase全身静脉溶栓治疗组(IVT-HAase组)、生理盐水选择性动脉溶栓对照组(IAT-NaCl组)、HAase选择性动脉溶栓治疗组(IAT-HAase组),选择性动脉溶栓是通过舌动脉/面动脉/舌面干向颈外动脉主干置管完成的,术后4h、3天和7天行FA检查。将论文第三部分内容中20μl组的结果作为单纯栓塞对照组(Control组),比较五组术后7天皮瓣灌注面积百分比的差异。三、研究结果1.枕动脉、颞浅动脉、上颌动脉、面动脉和舌动脉是兔颈外动脉的5个主要分支,虽然它们在颈外动脉发出的位置存在较大的解剖变异,但发出后各自的走行方向恒定。兔耳为多源性血供模式,起源于耳后动脉的耳廓后动脉是最为重要的供血动脉,在耳廓近端与耳后静脉内侧支伴行。2.成功建立以耳廓后动脉和耳后静脉内侧支为供血动脉和回流静脉的兔耳岛状皮瓣,术后皮瓣灌注良好并完全成活。3.术后4h,FA检查荧光斑驳、强弱不等,无法计算灌注面积。除术后24h 10 u 1组皮瓣灌注面积百分比与20 μl组结果相比无明显差异外,其它所有时间点10μl组结果均显著性高于20 u 1组,20μl组结果亦显著性高于40μl组(P0.05)。HA阻塞处的动脉和静脉可有嗜酸性粒细胞浸润。术后7天观察,蒂部被HA栓塞的耳廓后动脉自行再通。4.术后7天,Control组、IVT-NaCl组、IVT-HAase组、IAT-NaCl组、IAT-HAase皮瓣平均灌注面积百分比分别为76.54±6.92、74.08±9.14、76.94±6.68、76.95±8.72和95.47±3.38。IAT-HAase组皮瓣灌注面积百分比显著性高于其它四组(P0.05),其它四组结果两两相比均无明显差异。四、结论1.颈外动脉的分支情况具备经舌动脉/面动脉/舌面干向颈外动脉主干置管、对颞浅动脉分支进行选择性动脉溶栓治疗的条件。耳廓血管解剖具备以耳廓后动脉和耳后静脉内侧支作为供血动脉和回流静脉制作岛状皮瓣的条件。2.兔耳岛状皮瓣灌注良好、完全成活,可以以此为基础制作HA动脉栓塞皮肤缺血模型。3.成功建立HA动脉栓塞皮肤缺血模型。动脉被完全栓塞后,皮瓣将出现不同程度的再灌注,术后同一时间,栓塞剂量越大,皮瓣再灌注范围越小,皮瓣坏死面积越大。被HA栓塞的动脉是有自行再通可能的。HA动脉栓塞可引起血管炎。4. HAase选择性动脉溶栓能够有效改善HA动脉栓塞引起的皮瓣缺血、增加组织灌注、缩小皮瓣坏死面积。HAase全身静脉溶栓的疗效有待进一步研究。
[Abstract]:A study, 1. master of rabbit neck and ear vascular anatomic distribution and, for the establishment of rabbit ear flap and external carotid artery by selective thrombolytic therapy lay the anatomical basis of.2. rabbit ear flap, for the establishment of hyaluronic acid based (hyaluronic acid HA) embolization skin ischemia model.3. lay the foundation to establish the rabbit ear flap artery embolism HA skin ischemia model, comparison of different doses of HA after embolization flap perfusion difference area, change the.4. to verify the intravascular hyaluronidase pathological observation vessels (hyaluronidase, HAase) for the treatment of HA artery embolism skin ischemic lesion effect, comparison of intravenous thrombolysis and selective arterial thrombolysis treatment. Two research methods 1. experimental 8 rabbits by chemical method of vascular cast, making cast specimens of head and neck vascular, observe the neck and ears Department of vascular anatomy experiment.2. 5 rabbits, making 2.5 * 6cm, the posterior auricular artery and the medial branch of the posterior auricular vein pedicled island flap after operation. 4h, 24h, 3 days, 5 days and 7 days after angiography (fluorescein angiography FA) examination, observation of flap perfusion and survival.3. the 18 white rabbits, making the island flap, the posterior auricular artery injection of HA, according to the different injection volume is divided into 10 L, 20 1 and 40 l group. After 4h, 24h, 3 days, 5 days and 7 days after the FA examination, the difference between the three groups at the same time points of flap perfusion the area percentage were observed. After 7 days of 24h and vascular pathological changes in.4. experiment, 20 rabbits produced the first 20 lHA artery skin ischemia model, according to the different treatment methods were divided into 4 groups: normal saline intravenous thrombolysis group (IVT-NaCl group), HAase intravenous thrombolytic therapy group (IVT-HAase group) saline, selective Arterial thrombolysis group (IAT-NaCl group), HAase selective arterial thrombolysis treatment group (IAT-HAase group), selective arterial thrombolysis through lingual artery / face / artery truncus linguofacialis to external carotid artery trunk catheter complete, postoperative 4h, 3 days and 7 days after FA examination. The third part of the thesis in 20. L group as a result of the simple embolization control group (group Control), the difference between the 7 day perfusion area percentage were compared between the five groups. Results three, 1. occipital artery, superficial temporal artery, maxillary artery and facial artery, lingual artery is the 5 main branches of the external carotid artery, although anatomy variation they are larger in the external carotid artery from the position, but after the issue of their direction is constant. The rabbit ear for sources of blood supply pattern, auricle originated from the posterior auricular artery artery is one of the most important arteries in the auricle proximal medial branch of the posterior auricular vein and the accompanying.2. successfully established by ear Profile after artery and medial branch of the posterior auricular vein to artery and vein of the rabbit ear flap, flap perfusion and survived completely after.3. 4h, FA fluorescent mottled, different strength can not be calculated. In addition, perfusion area after 24h 10 U 1 flap perfusion group area percentage and 20 mu l results no significant difference, all the other 10 time points of l group, the results were significantly higher than those of 20 U 1 group, 20 l group also was significantly higher than that of 40 l group (P0.05).HA blockage of arteries and veins with eosinophilic infiltration. After 7 days of observation, pedicle by the 7 day, HA plug after ear artery to recanalization after.4. Control group, IVT-NaCl group, IVT-HAase group, IAT-NaCl group, IAT-HAase flap average perfusion area percentages were 76.54 + 6.92,74.08 + 9.14,76.94 + 6.68,76.95 + 8.72 and 95.47 + 3.38.IAT-HAase group flap perfusion area percentage was significant Higher than the other four groups (P0.05), the other four groups of 22 results showed no significant difference. Four branches, 1. conclusions of external carotid artery with the lingual artery / face / artery truncus linguofacialis to external carotid artery trunk catheter, selective arterial thrombolysis treatment condition of the branches of superficial temporal artery vascular anatomy with auricle..2. rabbit ear flap perfusion with posterior auricular artery and the medial branch of the posterior auricular vein artery and vein as making island flap survived completely, well, can serve as a basis for making.3. artery embolization skin ischemia model HA successfully established HA artery embolization skin ischemia model. Artery was completely after embolization, the flap will appear reperfusion in different degree, at the same time, the greater the embolization dose, flap reperfusion is smaller, flap necrosis area larger. HA artery embolization is a self recanalization.HA artery embolization may lead Selective arteriolytic thrombolysis with.4. HAase can effectively improve the ischemia of skin flap caused by HA artery embolization, increase tissue perfusion and reduce the area of flap necrosis..HAase systemic intravenous thrombolysis needs further study.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R-332;R764

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