主動(dòng)脈夾層動(dòng)脈瘤實(shí)驗(yàn)動(dòng)物模型的建立
發(fā)布時(shí)間:2018-04-08 17:50
本文選題:主動(dòng)脈 切入點(diǎn):夾層動(dòng)脈瘤 出處:《同濟(jì)大學(xué)》2005年碩士論文
【摘要】: 目的:探討DebakeyⅢ型夾層動(dòng)脈瘤實(shí)驗(yàn)動(dòng)物模型建立的方法及注意事項(xiàng),在較為接近病理生理?xiàng)l件下形成夾層動(dòng)脈瘤,為夾層動(dòng)脈瘤形成和發(fā)展的研究提供實(shí)驗(yàn)基礎(chǔ)和實(shí)驗(yàn)手段,為臨床探討選擇主動(dòng)脈夾層動(dòng)脈瘤治療新途徑提供可靠的動(dòng)物模型和實(shí)驗(yàn)依據(jù)。 材料與方法:5-7月齡、體重12-16kg的健康家豬(雌雄不限)12頭,隨機(jī)分為高脂飼料組(n=6)和普通飼料組(n=6)進(jìn)行飼養(yǎng),分別于飼養(yǎng)前、飼養(yǎng)后第4周、第8周測血脂水平,并記錄體重。隨后在氣管插管全麻下建立夾層動(dòng)脈瘤模型。術(shù)前測量正常主動(dòng)脈直徑,以距左鎖骨下動(dòng)脈遠(yuǎn)端2-3cm處為起始處,以0T針刺入降主動(dòng)脈中膜,注入彈性蛋白酶200U分解彈力蛋白層,利用機(jī)械膨脹力使中膜與內(nèi)膜分離,分離長度5-7cm左右,術(shù)中可見主動(dòng)脈明顯鼓起。在鼓起的主動(dòng)脈上下兩端分別用阻斷鉗阻斷主動(dòng)脈,尖頭刀迅速切開主動(dòng)脈管壁全層,用自制的動(dòng)脈壁分離器分離主動(dòng)脈中膜和內(nèi)膜,并剪掉部分內(nèi)膜,分離周徑為主動(dòng)脈周徑的1/3-1/2。然后用無損傷側(cè)壁鉗鉗夾切開處的主動(dòng)脈,5-0prolene線縫合外膜和中層,開放主動(dòng)脈,夾層模型建立成功。隨后靜脈注射腎上腺素0.5-1mg以升高血壓,加速夾層的剝離,測量夾層形成處主動(dòng)脈直徑。術(shù)后采用抗凝等措施防止夾層內(nèi)血栓形成,并行MRI檢查證實(shí)夾層的存在。動(dòng)物術(shù)后死亡者立即開胸,取降主動(dòng)脈行大體觀察和組織學(xué)檢查。所得數(shù)據(jù)均以均數(shù)±標(biāo)準(zhǔn)差表示,應(yīng)用SAS6.12軟件進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料的比較采用t檢驗(yàn),檢驗(yàn)水準(zhǔn)設(shè)為以α=0.05。 結(jié)果:①高脂飼料組動(dòng)物4周后血總膽固醇、低密度脂蛋白、載脂蛋白B水平較喂飼前明顯上升(P0.01),8周后上升更顯著(P0.001);血甘油三脂水平4周后與喂飼前相比無顯著性差異(P0.05),8周后明顯上升(P0.01):高密度脂蛋白在第4周及8周雖有所上升(P0.01,P0.001),但高密度脂蛋白/總膽固醇、高密度脂蛋白/低密度脂蛋白于第8周均顯著下降(P0.01,P0.001)。普通飼料組動(dòng)物在實(shí)驗(yàn)前及第4周和第8周的血脂水平基本接近,無顯著性差異(P0.05)。兩組動(dòng)物體重差異無顯著性(P0.05)。高脂飼料組動(dòng)物的基礎(chǔ)血壓較普通飼料組動(dòng)物高,分別為190-200/160-170mmHg,140-150/110-120mmHg。②高脂飼料組6只動(dòng)物中,,3只動(dòng)物死亡,檢查發(fā)現(xiàn)2只動(dòng)物有夾層形成;普通飼料組6只動(dòng)物中,2只動(dòng)物死亡,檢查發(fā)現(xiàn)僅1只動(dòng)物有夾層形成。③高脂飼料組和普通飼料組動(dòng)物術(shù)前主動(dòng)脈直徑分別為1.0-1.4cm、0.9-1.3cm,夾層形成處主動(dòng)脈直徑分別為1.8-2.2cm、1.6-1.8cm,均較術(shù)前明顯增粗,且高脂飼料組增大明顯。④死亡動(dòng)物立即取下降主動(dòng)脈,標(biāo)本肉眼可見內(nèi)膜破口,中層與內(nèi)膜分離,瘤壁變薄。光鏡下高脂飼料組動(dòng)物的主動(dòng)脈壁可見內(nèi)皮隆起、變形,管壁炎癥反應(yīng)明顯,內(nèi)膜下有泡沫細(xì)胞沉積等,Weigert彈力纖維染色可見夾層動(dòng)脈瘤處彈力層斷裂、溶解、破碎。普通飼料組主動(dòng)脈切片在光鏡下見內(nèi)膜完整,管壁結(jié)構(gòu)層次清晰,Weigert彈力纖維染色可見完整的波浪狀彈力層。 結(jié)論:①由于主動(dòng)脈內(nèi)膜損傷,形成破口,血液經(jīng)內(nèi)膜破孔進(jìn)入主動(dòng)脈中層,在高壓下將主動(dòng)脈分為雙層,形成主動(dòng)脈間血腫并進(jìn)一步剝離、擴(kuò)展,造成假腔,形成夾層動(dòng)脈瘤。夾層的假腔可經(jīng)第二處破口與真腔溝通。主動(dòng)脈中層彈力纖維退變斷裂、囊性壞死是本病的病理基礎(chǔ);高血壓病、動(dòng)脈粥樣硬化是常見的病因。②該建模方法符合夾層動(dòng)脈瘤形成的病變基礎(chǔ)及病理生理過程,是科學(xué)的,可行的。③術(shù)前喂飼高脂飲食可造成一定程度高脂血癥,基礎(chǔ)血壓升高,動(dòng)脈處于早期硬化表現(xiàn),符合夾層動(dòng)脈瘤的病理基礎(chǔ),利于模型的建立;彈性蛋白酶可消融彈力纖維層,解除其彈力回縮作用,利于瘤壁的擴(kuò)張。④該實(shí)驗(yàn)方法可為臨床診斷疾病及探討選擇主動(dòng)脈夾層動(dòng)脈瘤治療新途徑提供可靠的動(dòng)物模型和實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective: to establish a method of Debakey type III dissection animal model and the matters needing attention, the formation of dissecting aneurysm in pathology is close to physiological conditions, and the development of the research provides the experimental basis and experimental methods for dissection, clinical study provides a reliable animal model and experimental basis for a new way of treatment for aortic dissection aneurysm.
Materials and methods: 5-7 months old, weighing 12-16kg healthy pigs (male or female) 12, were randomly divided into high-fat diet group (n=6) and normal diet group (n=6) were fed, respectively before breeding, fourth weeks after feeding for eighth weeks, measured serum lipid levels, and record the weight. Then in the air intubation under general anesthesia to establish model of dissecting aneurysm. Preoperative measurement of normal aortic diameter, distance to distal to the left subclavian artery at 2-3cm at the beginning, with 0T needle in the descending aorta in film, injection of elastase 200U decomposition of elastin layer, expansion force of membrane separation and membrane separation by using a mechanical length of about 5-7cm there were visible aortic obvious bulge in the muster of the aorta. The upper and lower ends are respectively clamped aorta, aortic wall incision knife tip rapidly with full thickness, intimal and arterial wall separating aortic homemade, and cut off part of the intima, the separation of week Diameter of aortic circumference 1 / 3-1 / 2. and no damage to wall incision aortic clamp, 5-0prolene suture outer and middle aortic dissection model was established successfully. Then, intravenous injection of epinephrine 0.5-1mg to increase blood pressure, accelerate the interlayer peeling, measuring the diameters of the aorta dissection. After the operation anticoagulation and other measures to prevent the interlayer of thrombosis, parallel MRI examination confirmed the existence of dissection of aorta. Death animal after surgery immediately, take the descending aorta for gross observation and histological examination. The data were expressed as the mean + SD., SAS6.12 software was used for statistical analysis, measurement data were analyzed by using t test, test set the standard for a =0.05.
Results: the high fat diet group animal after 4 weeks, serum total cholesterol, low density lipoprotein, apolipoprotein B levels were fed with significantly increased (P0.01), after 8 weeks rose more significantly (P0.001); blood lipid level of three glycerol after 4 weeks and the Fed had no statistically significant difference (P0.05), after 8 weeks was significantly increased (P0.01), high density lipoprotein in fourth weeks and 8 weeks has increased (P0.01, P0.001), but the high density lipoprotein and total cholesterol, high density lipoprotein and low density lipoprotein in eighth weeks were significantly decreased (P0.01, P0.001). Normal diet group animal close to the lipid level in the experiment before and 4 weeks and eighth weeks, there was no significant difference (P0.05). Two groups of animal weight had no significant difference (P0.05). The blood pressure of high fat diet group than that of the normal animal feed group animal, respectively, 190-200 / 160-170mmHg, 140-150 / 110-120mmHg. in high fat diet group 6 Animal, 3 animal deaths, found in 2 animal dissection; normal diet group 6 animal, 2 animal deaths, inspection found only 1 animal dissection. The high fat diet group and normal diet group animal preoperative aortic diameter were 1.0-1.4cm, 0.9-1.3cm, dissection at aortic diameters were 1.8-2.2cm, 1.6-1.8cm, were significant thickening, and high fat diet group increased significantly. The dead animal immediately take down aortic specimens, visible intimal tear, separating the middle and inner membrane, aneurysm wall thinning. Light microscopy of aortic wall under high fat diet group animal shows endothelial uplift and deformation the tube wall, inflammation, intimal foam cell deposition, staining of dissecting aneurysm at the elastic layer fracture, Weigert elastic fibers dissolved and broken. The normal diet group aortic sections in the light microscope to see intimal end The structure of the tube wall is clear and the Weigert elastic fiber can be dyed with a complete wave elastic layer.
Conclusion: the aortic intimal injury, the formation of breach, the blood by the hole into the medial aortic intima, under high pressure will be divided into double aortic, aortic hematoma between and further stripping, expansion, resulting in false lumen formation of dissecting aneurysm. Dissection false lumen through second break communication with the true lumen of aortic media. The degeneration of elastic fibers fracture, cystic necrosis is the pathological basis of this disease; hypertension, atherosclerosis is a common cause. The modeling method is consistent with the pathological basis and pathophysiology of dissection, is scientific, feasible. The preoperative feeding high fat diet can cause a certain degree of hyperlipidemia the foundation, elevated blood pressure, artery in early stage of sclerosis, with the pathological basis of dissecting aneurysm, to establish model; elastase ablation elastic fibers and lift its elastic recovery effects, and The experimental method can provide reliable animal models and experimental evidence for clinical diagnosis of disease and the new way to select aortic dissection aneurysm.
【學(xué)位授予單位】:同濟(jì)大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2005
【分類號(hào)】:R-332;R654.3
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