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急性腸系膜缺血模型的制作與實驗研究及缺血修飾蛋白對腸缺血臨床診斷的初步探討

發(fā)布時間:2018-12-21 07:42
【摘要】:背景目的:急性腸系膜缺血早期診斷困難,致死致殘率極高。近年來發(fā)病率有增高的趨勢。有關于AMI的基礎研究多是在以血管結扎為基礎的動物模型上進行的。動脈結扎的模型只能模擬AMI的極端情況。急性腸系膜上靜脈血栓形成則較靜脈結扎的差別更大。研究模型不能代表臨床發(fā)病的病理生理過程必然導致研究結果的偏差,F已有較多的關于激光導致血管狹窄甚至閉塞的報道。本實驗擬采用激光直接照射腸系膜血管的方式致急性腸系膜血管狹窄,獲得急性腸系膜缺血的模型,并觀察模型中血清學標記物的變化。 材料與方法:以實驗大鼠開腹游離腸系膜動靜脈后采用不同的激光參數分別照射動、靜脈,縫合關腹觀察。24小時后再次開腹觀察,與腸系膜動靜脈結扎的動物比較,探索導致急性腸系膜缺血的激光參數。找出理想的激光參數后取SD大鼠66只,隨機分為11組,每組均為6只。C0、C1、C2組為對照組,分別在開腹游離腸系膜血管后即刻、1小時和2小時留取血液和腸管標本。A1、A2、T1組照射動脈;V1、V2、P1、P2、T2組為照射靜脈。A1、V1組照射后1小時留取血液和腸管標本;A2、V2組于2小時留取血液和腸管標本;T1、T2組照射血管后15分鐘內給予尾靜脈內注射尿激酶,于2小時留取血液和腸管標本;P1、P2組照射靜脈后于1小時、2小時取腸系膜上靜脈血液標本。 結果:以適當的激光參數直接照射腸系膜血管可以造成大鼠急性腸系膜缺血損傷模型,,不同的激光參數可以導致不同程度的腸缺血。模型中各組血清D二聚體有升高趨勢,但與對照組相比沒有統(tǒng)計學差異。體循環(huán)血液和門靜脈內血液D二聚體水平相近,無統(tǒng)計學差別。腸型脂肪酸結合蛋白的含量在照射動脈或靜脈后2小時均明顯升高,與對照組相比有統(tǒng)計學差異。溶栓治療對模型組動物的血清學指標和病理學表現無保護作用。缺血修飾白蛋白在大鼠模型各組之間無統(tǒng)計學差別;在臨床腸系膜缺血病例(共10例)中陽性率為100%。缺血修飾蛋白在腸系膜缺血病人中比急性心肌梗死病人升高的幅度更高,具有統(tǒng)計學差別。 結論:激光直接照射可形成急性腸系膜缺血的大鼠模型,急性腸系膜缺血時血清D二聚體升高,但無統(tǒng)計學差別;體循環(huán)血液標本D二聚體濃度與門靜脈血液一致。腸型脂肪酸結合蛋白在2小時時明顯升高,提示對診斷急性腸系膜缺血有意義。缺血修飾蛋白在動物模型中無變化,但是在臨床病例中陽性率高。
[Abstract]:Background: early diagnosis of acute mesenteric ischemia is difficult and the rate of death and disability is very high. The incidence of disease has been increasing in recent years. Basic research on AMI is mostly done on animal models based on vascular ligation. The model of artery ligation can only simulate the extreme case of AMI. Acute superior mesenteric venous thrombosis is more different than that of venous ligation. The research model can not represent the pathophysiological process of clinical pathogenesis, which inevitably leads to the deviation of the research results. There have been more reports of laser-induced stenosis or occlusion of blood vessels. In this experiment, the acute mesenteric vessel stenosis was induced by direct laser irradiation to mesenteric vessels, and the model of acute mesenteric ischemia was obtained, and the changes of serological markers in the model were observed. Materials and methods: different laser parameters were used to irradiate the arteries and veins of the free mesenteric arteries and veins of the experimental rats, and to suture the closed abdomen for observation. After 24 hours, the rats were observed again, and compared with the animals with mesenteric arteriovenous ligation, and the results were compared with those of the animals with mesenteric arteriovenous ligation. To explore the laser parameters leading to acute mesenteric ischemia. After finding out the ideal laser parameters, 66 SD rats were randomly divided into 11 groups (6 rats in each group). Group A _ 2T _ 1 irradiated artery; The blood and intestinal specimens were collected 1 hour after irradiation in A1V1 group, and those in A2V2 group were retained at 2 hours after irradiation. Urokinase was injected into caudal vein within 15 minutes after irradiation in T _ 1T _ 2 group, blood and intestinal specimens were collected at 2 hours, and blood samples of superior mesenteric vein were collected at 1 hour and 2 hours after irradiation in P _ 1 / P _ 2 group. Results: rat models of acute mesenteric ischemia injury could be induced by direct irradiation of mesenteric vessels with appropriate laser parameters, and different laser parameters could lead to different degrees of intestinal ischemia. In the model, serum D dimer tended to increase, but there was no statistical difference compared with the control group. The level of D dimer in blood of systemic circulation and portal vein was similar, but there was no statistical difference. The content of intestinal fatty acid binding protein increased significantly at 2 hours after irradiation of artery or vein, which was significantly different from that of control group. Thrombolytic therapy had no protective effect on the serological indexes and pathological manifestations of the model group. The positive rate of ischemia modified albumin was 100 in 10 cases of mesenteric ischemia. Ischemic modified proteins were significantly higher in patients with mesenteric ischemia than in patients with acute myocardial infarction. Conclusion: the rat model of acute mesenteric ischemia can be established by direct laser irradiation. The serum D dimer level is increased in acute mesenteric ischemia, but there is no statistical difference, and the concentration of D dimer in blood samples of systemic circulation is consistent with that of portal vein blood. Intestinal fatty acid binding protein increased significantly at 2 hours, suggesting that it is of significance in the diagnosis of acute mesenteric ischemia. Ischemic modified protein did not change in animal model, but the positive rate was high in clinical cases.
【學位授予單位】:中國人民解放軍醫(yī)學院
【學位級別】:博士
【學位授予年份】:2014
【分類號】:R572.3

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