本文關(guān)鍵詞： 急性肺血栓栓塞 肺動脈高壓 IL-13 TGF-β 動物模型　出處：《天津醫(yī)科大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：肺血栓栓塞癥(Pulmonary thromboembolism, PTE)為來自靜脈系統(tǒng)或右心的血栓阻塞肺動脈或其分支所致的疾病,以肺循環(huán)和呼吸功能障礙為主要臨床和病理生理特征。目前對于PTE在分子及細(xì)胞水平的病理生理了解尚少,多數(shù)學(xué)者認(rèn)為肺栓塞的病理進(jìn)程與炎癥反應(yīng)有關(guān)。最近有文獻(xiàn)報道了肺動脈重建中的免疫學(xué)發(fā)病機(jī)理。本文提出假設(shè)認(rèn)為PTE后肺動脈重建與炎癥反應(yīng)及免疫反應(yīng)相關(guān),并進(jìn)行論證。 IL-13是由不同T細(xì)胞亞群和樹突狀細(xì)胞產(chǎn)生的多效能細(xì)胞因子,主要由Th2細(xì)胞分泌。有文獻(xiàn)報道IL-13系統(tǒng)是肺動脈平滑肌細(xì)胞生長的新型調(diào)節(jié)系統(tǒng)。 此外,IL-13可以誘導(dǎo)潛在TGF-β的產(chǎn)生,間接激活TGF-β。同時,低氧也可促進(jìn)TGF-β表達(dá)增高。而TGF-β是調(diào)控細(xì)胞增殖、分化的重要因子,能促進(jìn)血管平滑肌細(xì)胞增殖、表型轉(zhuǎn)化及血管重構(gòu),與多種心血管疾病發(fā)生密切相關(guān)。 本課題詣在建立急性肺血栓栓塞模型,觀察肺栓塞的病理改變,并探討IL-13、TGF-β在PTE肺動脈重建中的作用。 方法：本課題分三部分進(jìn)行： 第一部分：日本大耳白36只,隨機(jī)分為急性肺血栓栓塞模型組18只、對照組18只。模型組采用自體血栓回輸法建立PTE模型,對照組給予等量0.9%氯化鈉溶液,經(jīng)數(shù)字減影血管造影及病理學(xué)檢查確定模型建造成功與否。 第二部分：分別于48h、4d、14d采集模型組和對照組肺動脈及周圍肺組織,行HE染色及Masson染色進(jìn)行病理學(xué)分析。 第三部分：分別于48h、4d、14d采集模型組及對照組血清,應(yīng)用酶聯(lián)免疫吸附試驗方法(ELISA)檢測IL-13、TGF-β含量。 實驗數(shù)據(jù)采用SPSS 13.0統(tǒng)計軟件進(jìn)行統(tǒng)計學(xué)分析,數(shù)據(jù)以均數(shù)±標(biāo)準(zhǔn)差表示,組內(nèi)不同時間點(diǎn)比較采用方差分析(One-Way ANOVA),各組間均數(shù)比較采用t檢驗(t-test analysis),數(shù)據(jù)相關(guān)性分析采用Pearson檢驗,均以P0.05為差異有統(tǒng)計學(xué)意義。 結(jié)果：第一部分：對22只實驗兔進(jìn)行造模,成功制作18只PTE模型。未成功的4只動物中,1只死于麻醉意外,3只死于大面積栓塞,成功率為81.8%。栓塞水平多位于段肺動脈,以雙肺栓塞為主,下肺為著。RR、HR、AaDO2升高均發(fā)生于肺栓塞早期。 第二部分：受累肺動脈壁及遠(yuǎn)端肺動脈分別于第4天和第2天可見以中性粒細(xì)胞為主的炎癥細(xì)胞數(shù)量增加(P0.05)；于栓塞后第14天可見肺動脈內(nèi)膜明顯增厚(P0.05) 第三部分：肺栓塞后血清中IL-13、TGF-B水平分別于第4天和第14天升高,為36.86±3.06pg/mg、1591.67±55.01pg/mg,顯著高于對照組(P0.05)。結(jié)論：1.自體血栓回輸法制備急性肺動脈血栓栓塞動物模型成功率為81.8%,具有可重復(fù)性。栓子分布與臨床上栓子分布相似。AaDO2可作為肺栓塞的早期診斷指標(biāo)。RR及HR變化于肺栓塞后即刻出現(xiàn),但HR的恢復(fù)早于RR。 2.肺栓塞中,炎癥細(xì)胞浸潤不僅發(fā)生在受累肺動脈壁,也發(fā)生在遠(yuǎn)端肺動脈,均以中性粒細(xì)胞為主；肺泡間隔內(nèi)可見以中性粒細(xì)胞為主的大量炎性細(xì)胞浸潤,可見肺泡膨脹不全。闡明了PTE的病理學(xué)改變與炎癥細(xì)胞浸潤相關(guān)。 3.在肺栓塞進(jìn)程中Th2型免疫反應(yīng)占有一定地位,IL-13與TGF-B共同促進(jìn)膠原產(chǎn)生,導(dǎo)致纖維化,參與肺動脈重建。但兩個指標(biāo)并無相關(guān)性。
[Abstract]:Objective: pulmonary thromboembolism (Pulmonary thromboembolism, PTE) from the venous system or right heart thromboembolism of pulmonary artery or its branches caused by the disease, pulmonary circulation and respiratory dysfunction as the main clinical and pathophysiological features. The PTE in the understanding of the pathophysiology of molecular and cellular level is less, the majority of scholars believe that the pathological process of inflammation and pulmonary embolism. Recently reported the immunological pathogenesis of pulmonary artery reconstruction. This paper proposed a hypothesis that related to pulmonary artery reconstruction and inflammation after PTE and immune response, and demonstrate.
IL-13 is a multipotent cytokine produced by different T cell subsets and dendritic cells, mainly secreted by Th2 cells. It has been reported that IL-13 system is a new regulation system for the growth of pulmonary artery smooth muscle cells.
In addition, IL-13 can induce the potential of TGF- beta, indirect activation of TGF- beta. At the same time, hypoxia may also promote the expression of TGF- increased. TGF- beta is an important factor in the regulation of cell proliferation, differentiation, can promote vascular smooth muscle cell proliferation, phenotype transformation and vascular remodeling, is closely related with various cardiovascular diseases.
This paper aims to establish models of acute pulmonary embolism, observe the pathological changes of pulmonary embolism, and to explore the role of IL-13, TGF- in beta PTE pulmonary artery reconstruction.
Methods: the subject was divided into three parts:
The first part: Japanese big ear white 36 rabbits were randomly divided into the model of acute pulmonary embolism in group 18, 18 rats in the control group. The model group using autologous blood transfusion method to establish the PTE model, the control group received the same amount of 0.9% Sodium Chloride Solution, by digital subtraction angiography and pathological examination to determine the model construction is successful or not.
The second part: the pulmonary artery and peripheral lung tissue were collected in 48h, 4D, 14d and control group respectively. The pathological analysis was performed by HE staining and Masson staining.
The third part: the serum of the model group and the control group were collected in 48h, 4D, 14d, and the content of IL-13 and TGF- beta was detected by enzyme linked immunosorbent assay (ELISA).
The experimental data were analyzed by SPSS 13 statistical software, data with the mean standard deviation of that group at different time points in comparison with analysis of variance (One-Way, ANOVA) among the groups were compared using t test (t-test analysis), the correlation analysis of data using Pearson test, P0.05 was considered statistically significant.
緇撴灉錛氱涓，

本文編號：1494485