肾脏损害和房颤发生的相关性和机制研究

发布时间：2018-05-12 09:28

本文选题：心房颤动 + 肾脏损害　；参考：《中国人民解放军医学院》2015年博士论文

【摘要】：背景与目的人群中房颤和慢性肾脏疾病患者人数都在急剧增加,近年来临床研究发现二者可能密切相关。理论上,交感神经系统激活可能是导致以上两种疾病的主要共同致病机制之一,肾脏损害可以导致全身交感活性增强,而交感活性增强可能直接影响心房电重构或通过激活肾素-血管紧张素-醛固酮系统而易于房颤的发生。而肾脏去神经化可以降低全身交感神经系统活性,可以成为防治房颤合并肾脏损害的切入点。本课题拟通过动物实验证实肾脏损害与房颤发生的相关性,并进一步探索其可能内在机制,尤其是交感神经系统在其中发挥的作用,为临床上合并肾脏损害房颤的防治提供新的思路。方法第一部分：通过明胶海绵栓塞比格犬左侧肾动脉小分支两周的方法建立单侧肾脏损害动物模型(模型组,n=5)。假手术组动物(n=5)不进行栓塞,但其他手术过程相同。比较两组动物造模前后的肾脏损害程度、肾功能、血压、左室压力和房颤诱发情况。比较两组动物造模前后交感神经活性、肾素-血管紧张素-醛固酮系统活性、炎症和氧化应激情况,以及心房组织纤维化程度。第二部分：在模型组(n=6)和肾脏去神经化组(n=6)通过明胶海绵栓塞比格犬右侧肾动脉小分支的方法建立单侧肾脏损害动物模型。假手术组动物(n=6)不进行栓塞,但其他手术过程相同。肾脏去神经化组动物栓塞后立即行肾脏去神经化射频消融术。比较各组动物造模前后的心脏电生理指标、血压、左室最大舒张末压、房颤诱发情况、交感神经活性、肾素-血管紧张素-醛固酮系统活性、炎症和氧化应激情况,以及心房组织纤维化程度。结果第一部分：栓塞左侧肾动脉小分支两周可以造成单侧肾脏缺血性损害。肾脏损害两周后实验动物可以发生以下变化：(1)心率增快和P波持续时间延长;(2)血压和左室最大收缩末压升高；(3)心房的不应期和房室结文氏点缩短;(4)房颤诱发率升高、持续时间延长,房颤时心房率和心室率增快;(5)血清去甲肾上腺素、肾素和醛固酮水平升高,心房组织血管紧张素Ⅱ、醛固酮水平升高,纤维化程度加重。第二部分：主要有5项发现：(1)栓塞右侧肾动脉小分支两周同样可以造成单侧肾脏缺血性损害;(2)肾脏去神经化可以完全或部分阻止肾脏损害导致的心率增快、P波持续时间延长和血压升高；(3)肾脏去神经化可以完全阻止肾脏损害引起的心房不应期缩短和房颤诱发率增加；(4)肾脏去神经化可以完全或部分阻止肾脏损害所导致的文氏点缩短、房颤时心房率和心室率的增快;(5)肾脏去神经化可以部分阻止肾脏损害所导致的血清去甲肾上腺素、肾素、醛固酮水平升高,部分阻止肾脏损害所导致的心房组织去甲肾上腺素、血管紧张素Ⅱ醛固酮、白介素-6、超敏C反应蛋白的升高以及纤维化程度的加重。结论1.成功建立肾脏损害合并轻度肾功能不全活体大动物模型,并在此模型基础上证实肾脏损害易于房颤的发生。2.应用此动物模型发现,交感神经系统激活可以促进合并肾脏损害房颤的发生,因为肾脏去神经化可以减少合并肾脏损害房颤的发生,缩短其持续时间。3.交感神经系统可能直接影响心房的电重构,或者间接激活RAAS、促进心房炎症和纤维化而发挥其促发房颤的作用。
[Abstract]:The number of patients with atrial fibrillation and chronic renal disease in background and objective population is increasing rapidly. In recent years, clinical studies have found that the two may be closely related. In theory, the activation of the sympathetic nervous system may be one of the major common pathogenic mechanisms leading to the above two diseases, and the renal damage can lead to the enhancement of the sympathetic activity of the whole body and the sympathetic activity. Enhancement may directly affect atrial electrical remodeling or activation of atrial fibrillation by activating the renin angiotensin aldosterone system. And renal neurodegeneration can reduce the activity of the systemic sympathetic nervous system and can be an entry point for the prevention and treatment of atrial fibrillation and renal damage. And further explore the possible internal mechanism, especially the role of the sympathetic nervous system, and provide new ideas for the prevention and treatment of atrial fibrillation in clinical combination. Method 1: a unilateral renal damage animal model was established by embolization of a small branch of the left renal artery in a beagle dog by a gelatin sponge for two weeks. Model group, n=5). The sham operation group (n=5) did not embolized, but the other operation process was the same. Compare the renal damage, renal function, blood pressure, left ventricular pressure and atrial fibrillation before and after the two groups of animal models. Compare the sympathetic activity before and after the two groups of animal models, the activity of renin angiotensin aldosterone system, inflammation and oxidation should be compared. The second part: the animal model of unilateral renal damage was established in the model group (n=6) and the kidney de neurochemical group (n=6) with a small branch of the right renal artery by gelatin sponge. The sham operation group (n=6) did not embolized, but the other surgical procedures were the same. The renal neurochemistry group was the same. The cardiac electrophysiological indexes, blood pressure, maximum left ventricular end diastolic pressure, atrial fibrillation, sympathetic activity, renin angiotensin aldosterone system activity, inflammation and oxidative stress, and the degree of fibrosis in the atrium were compared. Part: two weeks of embolization of the small branch of the left renal artery can cause unilateral renal ischemic damage. After two weeks of renal damage, the experimental animals can have the following changes: (1) heart rate increases and P wave duration prolonged; (2) blood pressure and left ventricular maximum systolic pressure increase; (3) atrial refractory period and atrioventricular node Venter's point shortening; (4) atrial fibrillation induced rate Elevated, prolonged duration, atrial rate and ventricular rate increased in atrial fibrillation; (5) serum norepinephrine, renin and aldosterone levels increased, atrial angiotensin II, aldosterone levels increased, and fibrosis increased. Second parts: (1) embolization of the small branch of the right renal artery for two weeks could also cause one side. Renal ischemic damage; (2) renal deneuration can completely or partially prevent kidney damage caused by rapid heart rate, P wave duration and blood pressure increase; (3) renal deneuration can completely prevent renal failure induced by renal impairment and atrial fibrillation induced rate increases; (4) renal deneuring can be completely or partially blocked. A decrease in Venter's point caused by renal damage and an increase in atrial rate and ventricular rate during atrial fibrillation; (5) renal deneuring can partially prevent kidney damage from the serum norepinephrine, renin, aldosterone levels, and partial inhibition of renal impairment induced by norepinephrine, angiotensin II aldosterone, and aldosterone The increase of -6, hypersensitive C reactive protein and the aggravation of fibrosis. Conclusion 1. a large animal model of renal impairment with mild renal insufficiency is successfully established. On the basis of this model, it is proved that renal damage is prone to atrial fibrillation. The.2. application of this animal model shows that the activation of the sympathetic nervous system can promote the combination of renal damage. The occurrence of atrial fibrillation, because the renal neurodegeneration can reduce the occurrence of renal impairment associated with renal damage, and shorten the duration of the.3. sympathetic nervous system may directly affect the electrical remodeling of the atrium, or indirectly activate RAAS, promote atrial inflammation and fibrosis and play its role in promoting atrial fibrillation.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R541.75;R692

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