急性次大面積肺血栓栓塞動物模型的建立及尿激酶動脈內(nèi)溶栓治療的實驗研究
本文選題:犬 切入點:急性次大面積肺栓塞 出處:《南京醫(yī)科大學(xué)》2010年碩士論文 論文類型:學(xué)位論文
【摘要】:目的 (1)用介入栓塞技術(shù)建立一種能用于影像學(xué)診斷與溶栓治療研究的犬急性次大面積肺血栓栓塞動物模型,并評價其技術(shù)上的可行性和穩(wěn)定性;(2)研究不同劑量尿激酶動脈內(nèi)溶栓治療犬急性次大面積肺血栓栓塞的療效和并發(fā)癥,探索尿激酶動脈內(nèi)溶栓的合理劑量;以及動脈內(nèi)溶栓治療犬急性次大面積肺血栓栓塞的可行性、安全性和有效性。資料和方法 (1)健康成年雜種犬8只,用介入技術(shù)建立急性次大面積肺血栓栓塞動物模型,分別在栓塞前、動物模型建立成功后(以下簡稱為栓塞后)及栓塞后2h監(jiān)測其一般情況變化、平均肺動脈壓(MPAP)、血氣分析(PaO2、PaCO2)、凝血指標(biāo)(PT、APTT、D-dimer),并觀察栓塞前后、栓塞后2h肺動脈血管造影的情況;造影結(jié)束后處死動物取肺組織行大體解剖及病理學(xué)檢查。 (2)健康成年雜種犬32只,用介入技術(shù)建立急性次大面積肺血栓栓塞動物模型,并隨機(jī)分為對照組(A組)、5000U/Kg溶栓組(B組)、10,000U/kg溶栓組(C組)、20,000U/kg溶栓組(D組)。分別在栓塞前后及治療后2h觀察其出血及一般情況,監(jiān)測平均肺動脈壓(MPAP)、PaO2、PT、APTT,并造影觀察栓塞前后、溶栓后2h肺動脈再通情況,然后處死動物行病理學(xué)檢查。 結(jié)果 (1)8只雜種犬全部成功制成急性次大面積肺血栓栓塞動物模型,栓塞后均出現(xiàn)不同程度的呼吸困難,口唇及舌部紫紺;與栓塞前比較MPAP值明顯升高、PaO2下降及D-dimer值不同程度升高,與栓塞前比較都有顯著性差異(P0.05);肺動脈造影示左下肺血流消失,肺動脈主干及其分支完全閉塞;大體解剖和病理學(xué)檢查證實左下肺動脈血管主干內(nèi)可見暗紅色血栓充填,鏡下見肺泡間隔增厚腫脹,肺泡內(nèi)少量滲出,肺內(nèi)出血,肺泡萎縮,血管內(nèi)血栓形成。 (2)32只雜種犬全部成功建立急性次大面積肺血栓栓塞動物模型,栓塞后均出現(xiàn)不同程度的呼吸困難,呼吸加深加快,口唇及舌部紫紺,治療后2h上述癥狀溶栓組較對照組不同程度好轉(zhuǎn),C、D組呼吸困難癥狀明顯好轉(zhuǎn),呼吸頻率接近栓塞前狀態(tài),口唇及舌紫紺明顯改善,其中D組有3只犬溶栓過程中穿刺部位出血,予以壓迫止血后好轉(zhuǎn);四組動物栓塞前后MPAP、PaO2有顯著性統(tǒng)計學(xué)差異(P0.01),各組間比較無統(tǒng)計學(xué)意義,PT和APTT無明顯統(tǒng)計學(xué)變化(P0.05);溶栓治療后B組MPAP、PaO2的變化與對照組無統(tǒng)計學(xué)差異,C組、D組治療后MPAP下降、PaO2上升,較對照組前明顯改善,有顯著性差異(P0.05),C組、D組之間治療后MPAP、PaO2的改善情況無明顯統(tǒng)計學(xué)意義(P0.05);三組溶栓組治療前后PT和APTT都有不同程度延長,但B組與對照組比較無統(tǒng)計學(xué)差別(P0.05),治療后C組、D組PT、APTT較對照組顯著延長(P0.05),D組較C組延長更加明顯(P0.05);栓塞后造影示各組左下肺動脈主干阻斷、閉塞,相應(yīng)肺組織血流消失,栓塞前后比較(P0.05);溶栓后造影示左下肺動脈主干及各分支完全或部分開通,腔內(nèi)圓形或不規(guī)則的充盈缺損,相應(yīng)肺組織血流完全或部分恢復(fù),B組與對照組比較無明顯改善(P0.05),C組、D組溶栓后血管再通情況與對照組比較有明顯統(tǒng)計學(xué)差異,但兩組間比較無統(tǒng)計學(xué)意義;大體解剖和病理學(xué)檢查證實A組犬左下肺體積腫脹,左下肺動脈血管主干內(nèi)可見暗紅色血栓充填,鏡下見肺泡間隔增厚腫脹,肺泡內(nèi)少量滲出,肺泡萎縮,血管內(nèi)血栓形成;B組左下肺動脈血管主干部分再通,標(biāo)本切面段及段以下分支可見肺動脈內(nèi)充滿暗紅色血栓,鏡下觀察肺泡間隔增厚腫脹,肺內(nèi)出血,肺泡萎縮,血管內(nèi)血栓形成;C、D組左下肺動脈血管主干完全通暢,部分段及段以下分支可見少量血栓,其中D組三只動物出現(xiàn)肺組織暗紅色出血區(qū),邊界不整齊,局部萎陷,鏡下觀察肺泡間隔增厚腫脹,肺內(nèi)出血。 結(jié)論 ①介入栓塞技術(shù)建立的犬急性次大面積肺栓塞動物模型具有創(chuàng)傷小、操作簡單、模型穩(wěn)定性好等優(yōu)點,為進(jìn)一步研究次大面積肺血栓栓塞的影像學(xué)診斷和溶栓治療提供了比較理想的途徑;②在犬急性次大面積肺栓塞后2h動脈內(nèi)尿激酶對血栓有顯著溶栓作用,劑量大或等于10,000U/Kg的血管再通率高,能夠較快的恢復(fù)阻塞的肺動脈血流,但劑量增加出血風(fēng)險大,10,000U/Kg是比較合理的治療劑量。
[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.
【學(xué)位授予單位】:南京醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2010
【分類號】:R563.5;R-332
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