急性次大面积肺血栓栓塞动物模型的建立及尿激酶动脉内溶栓治疗的实验研究

发布时间：2018-03-16 20:06

本文选题：犬　切入点：急性次大面积肺栓塞　出处：《南京医科大学》2010年硕士论文　论文类型：学位论文

【摘要】：目的 (1)用介入栓塞技术建立一种能用于影像学诊断与溶栓治疗研究的犬急性次大面积肺血栓栓塞动物模型,并评价其技术上的可行性和稳定性;(2)研究不同剂量尿激酶动脉内溶栓治疗犬急性次大面积肺血栓栓塞的疗效和并发症,探索尿激酶动脉内溶栓的合理剂量;以及动脉内溶栓治疗犬急性次大面积肺血栓栓塞的可行性、安全性和有效性。资料和方法 (1)健康成年杂种犬8只,用介入技术建立急性次大面积肺血栓栓塞动物模型,分别在栓塞前、动物模型建立成功后(以下简称为栓塞后)及栓塞后2h监测其一般情况变化、平均肺动脉压(MPAP)、血气分析(PaO2、PaCO2)、凝血指标(PT、APTT、D-dimer),并观察栓塞前后、栓塞后2h肺动脉血管造影的情况;造影结束后处死动物取肺组织行大体解剖及病理学检查。 (2)健康成年杂种犬32只,用介入技术建立急性次大面积肺血栓栓塞动物模型,并随机分为对照组(A组)、5000U/Kg溶栓组(B组)、10,000U/kg溶栓组(C组)、20,000U/kg溶栓组(D组)。分别在栓塞前后及治疗后2h观察其出血及一般情况,监测平均肺动脉压(MPAP)、PaO2、PT、APTT,并造影观察栓塞前后、溶栓后2h肺动脉再通情况,然后处死动物行病理学检查。结果 (1)8只杂种犬全部成功制成急性次大面积肺血栓栓塞动物模型,栓塞后均出现不同程度的呼吸困难,口唇及舌部紫绀;与栓塞前比较MPAP值明显升高、PaO2下降及D-dimer值不同程度升高,与栓塞前比较都有显著性差异(P0.05);肺动脉造影示左下肺血流消失,肺动脉主干及其分支完全闭塞;大体解剖和病理学检查证实左下肺动脉血管主干内可见暗红色血栓充填,镜下见肺泡间隔增厚肿胀,肺泡内少量渗出,肺内出血,肺泡萎缩,血管内血栓形成。 (2)32只杂种犬全部成功建立急性次大面积肺血栓栓塞动物模型,栓塞后均出现不同程度的呼吸困难,呼吸加深加快,口唇及舌部紫绀,治疗后2h上述症状溶栓组较对照组不同程度好转,C、D组呼吸困难症状明显好转,呼吸频率接近栓塞前状态,口唇及舌紫绀明显改善,其中D组有3只犬溶栓过程中穿刺部位出血,予以压迫止血后好转;四组动物栓塞前后MPAP、PaO2有显著性统计学差异(P0.01),各组间比较无统计学意义,PT和APTT无明显统计学变化(P0.05);溶栓治疗后B组MPAP、PaO2的变化与对照组无统计学差异,C组、D组治疗后MPAP下降、PaO2上升,较对照组前明显改善,有显著性差异(P0.05),C组、D组之间治疗后MPAP、PaO2的改善情况无明显统计学意义(P0.05);三组溶栓组治疗前后PT和APTT都有不同程度延长,但B组与对照组比较无统计学差别(P0.05),治疗后C组、D组PT、APTT较对照组显著延长(P0.05),D组较C组延长更加明显(P0.05);栓塞后造影示各组左下肺动脉主干阻断、闭塞,相应肺组织血流消失,栓塞前后比较(P0.05);溶栓后造影示左下肺动脉主干及各分支完全或部分开通,腔内圆形或不规则的充盈缺损,相应肺组织血流完全或部分恢复,B组与对照组比较无明显改善(P0.05),C组、D组溶栓后血管再通情况与对照组比较有明显统计学差异,但两组间比较无统计学意义;大体解剖和病理学检查证实A组犬左下肺体积肿胀,左下肺动脉血管主干内可见暗红色血栓充填,镜下见肺泡间隔增厚肿胀,肺泡内少量渗出,肺泡萎缩,血管内血栓形成;B组左下肺动脉血管主干部分再通,标本切面段及段以下分支可见肺动脉内充满暗红色血栓,镜下观察肺泡间隔增厚肿胀,肺内出血,肺泡萎缩,血管内血栓形成;C、D组左下肺动脉血管主干完全通畅,部分段及段以下分支可见少量血栓,其中D组三只动物出现肺组织暗红色出血区,边界不整齐,局部萎陷,镜下观察肺泡间隔增厚肿胀,肺内出血。结论 ①介入栓塞技术建立的犬急性次大面积肺栓塞动物模型具有创伤小、操作简单、模型稳定性好等优点,为进一步研究次大面积肺血栓栓塞的影像学诊断和溶栓治疗提供了比较理想的途径;②在犬急性次大面积肺栓塞后2h动脉内尿激酶对血栓有显著溶栓作用,剂量大或等于10,000U/Kg的血管再通率高,能够较快的恢复阻塞的肺动脉血流,但剂量增加出血风险大,10,000U/Kg是比较合理的治疗剂量。
[Abstract]:objective
(1) by interventional technique can be used to establish a study of imaging diagnosis and thrombolytic therapy of acute submassive pulmonary embolism animal model, and to evaluate the technique feasibility and stability; (2) the effects of different doses of urokinase arterial thrombolysis for acute submassive pulmonary embolism curative effect and complications the reasonable dosage of urokinase, intra-arterial thrombolysis; and the feasibility of intra-arterial thrombolytic therapy for acute submassive pulmonary thromboembolism, the effectiveness and safety of materials and methods.
(1) 8 healthy mongrel canines to establish acute submassive pulmonary embolism animal model with interventional technique, respectively, before the embolism, successfully established animal model (hereinafter referred to as embolization) and embolization after 2H monitoring in general condition, mean pulmonary arterial pressure (MPAP), blood gas analysis (PaO2. PaCO2), blood coagulation index (PT, APTT, D-dimer), were observed before and after embolization, 2h pulmonary artery angiography after embolization; angiography after the animal were sacrificed and lung tissues were obtained for gross anatomy and pathological examination.
(2) 32 healthy mongrel canines to establish acute submassive pulmonary embolism animal model with interventional technique, and randomly divided into control group (A group), 5000U/Kg group (group B), thrombolysis 10000U/kg thrombolysis group (C group), 20000U/kg treatment group (D group) respectively before and after embolization and in. 2h after treatment to observe the bleeding and the general situation, monitoring the mean pulmonary arterial pressure (MPAP), PaO2, PT, APTT, and contrast observation before and after embolization, 2h after thrombolysis of pulmonary artery recanalization, then killed the animal pathology.
Result
(1) 8 dogs were successfully made acute submassive pulmonary embolism animal model after embolization showed varying degrees of difficulty in breathing, lip and tongue cyanosis; compared with before embolization, MPAP increased obviously, PaO2 decreased and D-dimer value increased, and the comparison before embolization, there was significant difference (P0.05); pulmonary artery angiography showed lower left pulmonary blood flow disappeared, pulmonary artery and branches occlusion; anatomy and pathology of left inferior pulmonary artery trunk can be seen in the dark red thrombi, microscopic alveolar septal thickening alveolar swelling, a small amount of effusion, pulmonary hemorrhage, alveolar atrophy, intravascular thrombosis.
(2) 32 dogs all successfully established acute submassive pulmonary embolism animal model after embolization showed varying degrees of difficulty in breathing, dyspnea, cyanosis, lips and tongue, 2h after treatment of the symptoms of thrombolysis group than in the control group improved in different degrees, C, D group of dyspnea symptoms improved markedly. The respiratory frequency is close to the state of the lips and tongue before embolization, cyanosis improved significantly in group D puncture site bleeding in 3 dogs during thrombolytic therapy, hemostasis to be improved after the four groups before and after embolization; animal MPAP PaO2, there was significant difference (P0.01), there was no significant difference between groups PT and APTT, there was no statistically significant change (P0.05); B group MPAP after thrombolytic therapy, the changes of PaO2 no significant difference compared with control group, C group, D group after treatment, MPAP decreased, PaO2 increased, compared with the control group improved significantly, there was significant difference (P0.05), C group, D group MPAP after treatment, The improvement of PaO2 was not statistically significant (P0.05); the three groups before and after thrombolytic therapy group PT and APTT have different degrees of extension, but the B group compared with the control group had no statistical difference (P0.05), after treatment, C group, D PT group, APTT was significantly longer than that of the control group (P0.05), D group than in C Yanchang formation is more obvious (P0.05); angiography after embolization showed lower left pulmonary artery occlusion, occlusion of the corresponding lung tissue blood flow disappeared, compared before and after embolization (P0.05) after thrombolysis; angiography showed lower left pulmonary artery and branches completely or partially opened, cavity round or irregular filling defect, complete recovery the corresponding part of the lung tissue or blood flow, no significant improvement compared with the control group, B group (P0.05), C group, D group, reperfusion after thrombolysis compared with the control group there was a significant difference, but no statistical significance between the two groups; the gross anatomy and pathological examination confirmed that the A group in left lower lung volume swelling Swelling, lower left pulmonary artery vascular trunk can be seen in the dark red thrombi, microscopic alveolar septal thickening and swelling, alveolar small exudation, alveolar atrophy, intravascular thrombosis; group B lower left pulmonary artery trunk vascular recanalization, the specimen section sections and branches visible in the pulmonary artery with dark red thrombus. Observation of alveolar septal thickening swelling, microscopic pulmonary hemorrhage, alveolar atrophy, intravascular thrombosis; C, group D lower left pulmonary artery trunk vascular patency completely, the following section and branch of a small amount of thrombus, three rats in D group animal lung tissue appeared dark red bleeding area, irregular borders, partial collapse, observation alveolar septal thickening swelling, with pulmonary hemorrhage.
conclusion
The interventional technique established in dogs with acute submassive pulmonary embolism animal model with small trauma, simple operation, good stability and other advantages of the model, provides an ideal method for the further study of submassive pulmonary embolism imaging diagnosis and thrombolytic therapy; the significant thrombolytic effect on thrombosis in dogs with acute large area pulmonary embolism after 2H intra-arterial urokinase, large dose or equal to 10000U/Kg, the recanalization rate is high, can quickly restore blood flow of pulmonary artery obstruction, but the dose increased risk of bleeding, 10000U/Kg treatment dose more reasonable.

【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R563.5;R-332

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