腹主動脈瘤小鼠模型的病理形態(tài)學(xué)比較及抗血管緊張素治療在其發(fā)病過程中的研究
發(fā)布時間：2018-08-22 21:30
【摘要】：第一章三種腹主動脈瘤小鼠模型的建立以及比較 目的：建立三種小鼠腹主動脈瘤(AAA)模型,比較三種建模方法的不同特點,探討其研究應(yīng)用的可行性。 方法：取C57BL/6以及ApoE-/-雄性小鼠共30只,采用三種不同方法分別建立三種小鼠腹主動脈瘤模型：血管緊張素Ⅱ模型[Angiotensin Ⅱ (Ang Ⅱ) Model],豬胰蛋白酶模型[Porcine Pancreatic Elastase(PPE) Model],氯化鈣模型[Calcium Chloride (CaCl2) Model];并用磷酸緩沖溶液(PBS)作為相應(yīng)方法的對照。多普勒超聲監(jiān)測小鼠腹主動脈直徑變化、成瘤部位,計算并比較不同小鼠腹主動脈瘤模型的建模方法、手術(shù)時間、成瘤時間、成瘤率以及死亡率等特點； 結(jié)果：三種方法均能建立成功的腹主動脈瘤模型。PPE模型建模方法難度較大,手術(shù)時間較長(52.6±5.1min),成瘤率高(100%),存活周期長(隨訪4周,存活率為95%),死亡率低(5%)；CaC12模型建模方法容易,手術(shù)時間較長(40.7±4.3min),成瘤率較低(50%),存活周期長(隨訪4周均存活,存活率為100%),死亡率低(0%)；AngⅡ模型建模方法容易,手術(shù)時間短(7.8±3.6min),成瘤率較高(70%),存活周期較短(隨訪4周,存活率為60%),死亡率較高(40%)。 結(jié)論：小鼠的PPE模型,CaC12模型以及Ang Ⅱ模型為三種較為穩(wěn)定的腹主動脈瘤模型,能為深入理解人腹主動脈瘤的病理機制以及評價腹主動脈瘤的藥物治療提供較為穩(wěn)定的研究平臺。 第二章三種腹主動脈瘤小鼠模型的病理形態(tài)學(xué)比較以及病理機制的研究 目的：觀察不同小鼠模型的病理形態(tài)學(xué)特點,探討不同腹主動脈瘤模型的共同病理機制。 方法：采用HE染色、EVG染色、免疫組織化學(xué)等方法檢測小鼠的腹主動脈瘤組織,與正常小鼠腹主動脈相比較,觀察病組織中瘤壁彈性纖維、炎癥細胞、新生血管、淋巴管生成等的表達差異。 結(jié)果：PPE模型腹主動脈瘤病理變化表現(xiàn)為外膜大量炎癥細胞浸潤(尤其以巨噬細胞為主,伴有T淋巴細胞以及少量B淋巴細胞)以及新生血管、淋巴管形成,彈力纖維變性,部分缺失斷裂,厚度不均。Ang Ⅱ模型表現(xiàn)為瘤壁血腫形成,外膜有炎癥細胞浸潤(以巨噬細胞為主,少有T淋巴細胞及B淋巴細胞)以及少量新生血管、淋巴管形成。伴有部分彈力纖維變性,缺失。CaCl2模型病變部位主要在外膜和中膜,表現(xiàn)為外膜部分增厚,伴少量炎癥細胞浸潤,僅有少量新生血管及淋巴管形成,中膜彈性纖維變性,僵直,呈燒灼狀,厚薄不均,部分缺失斷裂。 結(jié)論：三種小鼠模型既存在不同的病理形態(tài)學(xué)特點,也存在共同病理形態(tài)學(xué)特征,表現(xiàn)為炎癥細胞浸潤,血管及淋巴管生成。PPE、AngⅡ模型較為真實的反映了人腹主動脈瘤的病理特點,是兩種比較穩(wěn)定的動物模型。 第三章抗血管緊張素治療在腹主動脈瘤發(fā)生發(fā)展過程中的研究 目的：將血管緊張素受體阻滯劑應(yīng)用于小鼠腹主動脈瘤模型,評價抗血管緊張素治療在腹主動脈瘤中的應(yīng)用價值。 方法：取C57BL/6小鼠、ApoE-/-小鼠各15只,分成實驗組(10只/組)和對照組(5只/組),實驗組在建模前一周按telmisartan (10mg/kg)劑量給小鼠喂藥；另一組為對照組,正常飲食。分別用多普勒超聲監(jiān)測小鼠的腹主動脈直徑變化,與對照組(未用藥處理的腹主動脈瘤模型小鼠)相比較,比較不同小鼠的成瘤率,瘤體進展情況等。并應(yīng)用HE染色、EVG染色、免疫組織化學(xué)、qRT-PCR等方法檢測腹主動脈瘤組織,比較不同小鼠的病理形態(tài)學(xué)變化。 結(jié)果：telmisartan在10mg/kg的劑量下對小鼠無明顯副作用,能夠有效抑制彈力蛋白酶及血管緊張素灌注后的小鼠腹主動脈直徑進行性增大,并且能夠防止兩種腹主動脈瘤小鼠模型的腹主動脈瘤形成。病理切片顯示：telmisartan處理過的小鼠主動脈管壁血管生成明顯減少,炎癥細胞浸潤顯著減輕,彈性纖維以及管壁三層結(jié)構(gòu)相對完整,無顯著病理變化。 結(jié)論：抗血管緊張素治療能夠防止小鼠腹主動脈瘤的發(fā)生并控制疾病的進展。telmisartan能夠發(fā)揮有效的抗動脈瘤生成作用；10mg/kg的劑量安全,有效。
[Abstract]:Chapter 1 Establishment and comparison of three abdominal aortic aneurysm models in mice
Objective: To establish three models of abdominal aortic aneurysm (AAA) in mice and compare the different characteristics of the three models and explore the feasibility of their application.
Methods: C57BL/6 and ApoE-/- male mice were used to establish three kinds of abdominal aortic aneurysm models: Angiotensin II (AngII) model, Porcine Pancreatic Elastase (PPE) model and Calcium Chloride (CaCl2) model. Doppler ultrasonography was used to monitor the abdominal aorta diameter, tumor location, and to calculate and compare the modeling methods, operation time, tumor formation time, tumor formation rate and mortality of abdominal aorta aneurysm models in different mice.
Results: All three methods can establish successful abdominal aortic aneurysm models. PPE modeling method is difficult, the operation time is long (52.6 65 Ang II model has the advantages of easy modeling, short operation time (7.8 (+ 3.6 min), high tumor formation rate (70%), short survival period (60%) and high mortality (40%).
CONCLUSION: The PPE model, CaC12 model and Ang II model in mice are relatively stable models of abdominal aortic aneurysm, which can provide a stable research platform for further understanding the pathological mechanism of human abdominal aortic aneurysm and evaluating the drug treatment of abdominal aortic aneurysm.
The second chapter is about the pathomorphology comparison and pathological mechanism of three abdominal aortic aneurysm models in mice.
Objective: To observe the pathomorphological characteristics of different mouse models and explore the common pathological mechanism of different abdominal aortic aneurysm models.
Methods: HE staining, EVG staining and immunohistochemistry were used to detect the abdominal aortic aneurysm in mice. The expression of elastic fibers, inflammatory cells, neovascularization and lymphangiogenesis in the abdominal aorta of mice were compared with those of normal mice.
Results: The pathological changes of abdominal aortic aneurysm in PPE model were infiltration of a large number of inflammatory cells in the adventitia (especially macrophages with T lymphocytes and a small number of B lymphocytes) and neovascularization, lymphangiogenesis, elastic fibrosis, partial loss and rupture, and uneven thickness. The lesions in the CaCl2 model were mainly in the adventitia and mesangium, which showed partial thickening of the adventitia with a small amount of inflammatory cell infiltration, only a small amount of neovascularization and lymphatic vessel formation. The elastic fibers of the medial membrane are degenerated and stiff, with cauterization, uneven thickness and partial absence of fracture.
CONCLUSION: The three mouse models have different pathomorphological characteristics as well as common pathomorphological characteristics, such as inflammatory cell infiltration, angiogenesis and lymphangiogenesis. PPE and Ang II models reflect the pathological characteristics of human abdominal aortic aneurysm, and are two relatively stable animal models.
The third chapter is the study of anti angiotensin therapy in the development of abdominal aortic aneurysm.
AIM: To evaluate the value of antiangiotensin therapy in abdominal aortic aneurysm (AAA) by using angiotensin receptor blockers in mice.
METHODS: C57BL/6 mice and ApoE-/- mice were divided into experimental group (10 mice/group) and control group (5 mice/group), the experimental group was given telmisartan (10 mg/kg) one week before modeling, and the control group was given normal diet. The tumorigenesis rate and tumor progression of different mice were compared, and the abdominal aortic aneurysm tissues were detected by HE staining, EVG staining, immunohistochemistry, qRT-PCR and other methods.
Results: telmisartan had no obvious side effect on mice at the dose of 10 mg/kg. It could effectively inhibit the progressive enlargement of abdominal aorta diameter in mice perfused with elastase and angiotensin, and prevent the formation of abdominal aortic aneurysm in two kinds of abdominal aortic aneurysm mice. Vasculogenesis of aortic wall was significantly reduced, inflammatory cell infiltration was significantly reduced, elastic fibers and three-layer structure of aortic wall were relatively intact without significant pathological changes.
Conclusion: Antiangiotensin therapy can prevent the occurrence of abdominal aortic aneurysm and control the progress of the disease in mice.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R732.21;R-332
本文編號：2198351
[Abstract]:Chapter 1 Establishment and comparison of three abdominal aortic aneurysm models in mice
Objective: To establish three models of abdominal aortic aneurysm (AAA) in mice and compare the different characteristics of the three models and explore the feasibility of their application.
Methods: C57BL/6 and ApoE-/- male mice were used to establish three kinds of abdominal aortic aneurysm models: Angiotensin II (AngII) model, Porcine Pancreatic Elastase (PPE) model and Calcium Chloride (CaCl2) model. Doppler ultrasonography was used to monitor the abdominal aorta diameter, tumor location, and to calculate and compare the modeling methods, operation time, tumor formation time, tumor formation rate and mortality of abdominal aorta aneurysm models in different mice.
Results: All three methods can establish successful abdominal aortic aneurysm models. PPE modeling method is difficult, the operation time is long (52.6 65 Ang II model has the advantages of easy modeling, short operation time (7.8 (+ 3.6 min), high tumor formation rate (70%), short survival period (60%) and high mortality (40%).
CONCLUSION: The PPE model, CaC12 model and Ang II model in mice are relatively stable models of abdominal aortic aneurysm, which can provide a stable research platform for further understanding the pathological mechanism of human abdominal aortic aneurysm and evaluating the drug treatment of abdominal aortic aneurysm.
The second chapter is about the pathomorphology comparison and pathological mechanism of three abdominal aortic aneurysm models in mice.
Objective: To observe the pathomorphological characteristics of different mouse models and explore the common pathological mechanism of different abdominal aortic aneurysm models.
Methods: HE staining, EVG staining and immunohistochemistry were used to detect the abdominal aortic aneurysm in mice. The expression of elastic fibers, inflammatory cells, neovascularization and lymphangiogenesis in the abdominal aorta of mice were compared with those of normal mice.
Results: The pathological changes of abdominal aortic aneurysm in PPE model were infiltration of a large number of inflammatory cells in the adventitia (especially macrophages with T lymphocytes and a small number of B lymphocytes) and neovascularization, lymphangiogenesis, elastic fibrosis, partial loss and rupture, and uneven thickness. The lesions in the CaCl2 model were mainly in the adventitia and mesangium, which showed partial thickening of the adventitia with a small amount of inflammatory cell infiltration, only a small amount of neovascularization and lymphatic vessel formation. The elastic fibers of the medial membrane are degenerated and stiff, with cauterization, uneven thickness and partial absence of fracture.
CONCLUSION: The three mouse models have different pathomorphological characteristics as well as common pathomorphological characteristics, such as inflammatory cell infiltration, angiogenesis and lymphangiogenesis. PPE and Ang II models reflect the pathological characteristics of human abdominal aortic aneurysm, and are two relatively stable animal models.
The third chapter is the study of anti angiotensin therapy in the development of abdominal aortic aneurysm.
AIM: To evaluate the value of antiangiotensin therapy in abdominal aortic aneurysm (AAA) by using angiotensin receptor blockers in mice.
METHODS: C57BL/6 mice and ApoE-/- mice were divided into experimental group (10 mice/group) and control group (5 mice/group), the experimental group was given telmisartan (10 mg/kg) one week before modeling, and the control group was given normal diet. The tumorigenesis rate and tumor progression of different mice were compared, and the abdominal aortic aneurysm tissues were detected by HE staining, EVG staining, immunohistochemistry, qRT-PCR and other methods.
Results: telmisartan had no obvious side effect on mice at the dose of 10 mg/kg. It could effectively inhibit the progressive enlargement of abdominal aorta diameter in mice perfused with elastase and angiotensin, and prevent the formation of abdominal aortic aneurysm in two kinds of abdominal aortic aneurysm mice. Vasculogenesis of aortic wall was significantly reduced, inflammatory cell infiltration was significantly reduced, elastic fibers and three-layer structure of aortic wall were relatively intact without significant pathological changes.
Conclusion: Antiangiotensin therapy can prevent the occurrence of abdominal aortic aneurysm and control the progress of the disease in mice.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R732.21;R-332
【參考文獻】
相關(guān)期刊論文 前6條
1 張明芳;熊吉信;陳鋒;;腹主動脈瘤發(fā)病機制及其動物模型的研究進展[J];中國血管外科雜志(電子版);2010年03期
2 雷莉;血管內(nèi)皮細胞生長因子與治療性血管新生[J];中國心血管雜志;2001年05期
3 肖敏,呂軍,陳立東,劉峰松,張群林,黃從新;斑塊內(nèi)血管生成在兔動脈粥樣硬化斑塊發(fā)生發(fā)展中的作用[J];中國心血管雜志;2005年02期
4 張金保;張艷軍;崔廣智;莊朋偉;;動脈粥樣硬化斑塊內(nèi)新生血管與斑塊穩(wěn)定性的研究進展[J];中國藥理學(xué)通報;2011年07期
5 曹海勇,劉志成;動脈瘤動物模型的研究進展[J];中國醫(yī)學(xué)物理學(xué)雜志;2005年02期
6 孫璐,韋立新,石懷銀,郭愛桃,侯寧,游聯(lián)璧;冠狀動脈粥樣硬化斑塊內(nèi)血管新生與斑塊穩(wěn)定的關(guān)系[J];中華病理學(xué)雜志;2003年05期
，本文編號：2198351
本文鏈接：http://sikaile.net/xiyixuelunwen/2198351.html
最近更新
教材專著
