犬肾脏损害对房颤凝血及内皮功能的影响

发布时间：2018-06-15 09:49

本文选题：肾脏损害 + 心房颤动　；参考：《中国人民解放军医学院》2016年博士论文

【摘要】：背景与目的：随着年龄的增长,房颤的发病率随之增加。卒中是房颤最常见和严重的并发症,近20%的卒中由房颤引起,与非房颤患者相比,房颤增加4～5倍的卒中发生率。近年来慢性肾脏损害的发病率升高明显,肾脏损害可以增加血栓形成和出血的风险。房颤合并肾脏损害的人群发病率亦升高明显,该类人群的抗栓治疗目前还没有统一的评分标准和监测指标。本研究的主要目的是通过动物模型观察肾脏损害对房颤凝血指标和内皮功能的影响。本课题对进一步了解房颤合并肾脏损害患者的凝血和内皮功能变化有较重要的意义,从而为该类人群的抗栓治疗方案提供参考。方法第一部分：实验动物被随机分配到模型组(n=10)、单纯起搏组(n=5)和空白对照组(n=5)。利用明胶海绵栓塞比格犬单侧肾动脉主干1个月的方法建立急性肾脏损害动物模型。单纯起搏组及5只肾脏损害动物模型行右心房连续快速刺激3h建立房颤模型。比较肾脏栓塞组造模前后的肾脏功能、肾脏损害程度和刺激前后房颤诱发情况。比较单纯起搏组和动物模型组内皮功能、凝血指标、炎症和氧化应激情况、肾素-血管紧张素-醛固酮系统活性。第二部分：实验动物被随机分配到模型组(n=10)、单纯起搏组(n=5)和空白对照组(n=5),其中单纯起搏组和空白对照组同第一部分。利用明胶海绵栓塞比格犬单侧肾动脉主干3个月的方法建立慢性肾脏损害动物模型。单纯起搏组及5只肾脏损害动物模型行右心房连续快速刺激3h建立房颤模型。比较肾脏栓塞组造模前后的肾脏功能、肾脏损害程度和刺激前后房颤诱发情况。比较单纯起搏组、1个月动物模型组和3个月动物模型组内皮功能、凝血指标、炎症和氧化应激情况、肾素-血管紧张素-醛固酮系统活性。结果第一部分：栓塞单侧肾动脉主干1个月可以造成急性肾脏缺血性损害合并中度肾功能不全。右心房快速刺激3h可建立房颤模型。肾脏损害1个月后实验动物及右心房快速刺激后可发生如下变化：(1)心房不应期和房室结文氏点缩短；(2)房颤诱发率升高；(3)急性肾功能不全伴房颤较房颤组内皮功能受损轻,促凝血物质减少,纤溶系统功能增强,炎症及氧化应激反应轻。第二部分：栓塞单侧肾动脉主干3个月可以造成慢性肾脏缺血性损害合并中度肾功能不全。右心房快速刺激3h可建立房颤模型。肾脏损害3个月后实验动物及右心房快速刺激后可发生如下变化：(1)心房不应期和房室结文氏点缩短；(2)房颤诱发率升高；(3)慢性肾功能不全伴房颤较房颤组内皮功能受损严重,促凝物质增加,纤溶功能低下,炎症反应强,RAAS系统激活。(4)慢性肾功能不全伴房颤较急性肾功能不全伴房颤内皮功能受损严重,促凝物质增加,纤溶功能低下,炎症、氧化应激反应强,RAAS系统激活。结论1.成功建立急性和慢性肾脏损害合并中度肾功能不全活体大动物模型，并在此基础上成功建立房颤模型。2.应用该动物模型发现,急性肾损害合并中度肾功能不全伴房颤内皮功能损伤较轻,机体出血风险较大,血栓风险小。3.慢性肾损害合并中度肾功能不全伴房颤内皮功能损伤严重,血栓形成风险大,出血风险小。
[Abstract]:Background and purpose: the incidence of atrial fibrillation increases with age. Stroke is the most common and serious complication of atrial fibrillation, nearly 20% of stroke is caused by atrial fibrillation. Compared with non atrial fibrillation, atrial fibrillation increases by 4~5 times the incidence of stroke. In recent years, the incidence of chronic renal damage has increased significantly, and renal damage can increase thrombus shape. The risk of adult and bleeding. The incidence of atrial fibrillation combined with renal damage is also significantly higher. There is no unified standard and monitoring index for antithrombotic therapy in this group. The main purpose of this study is to observe the effect of renal damage on coagulation index and endothelial function of atrial fibrillation by animal model. The changes of coagulation and endothelial function in patients with renal impairment were of great significance, which provided a reference for the antithrombotic therapy of this group. Method first part: experimental animals were randomly assigned to model group (n=10), simple pacing group (n=5) and blank control group (n =5). The main trunk of renal artery was embolized by gelfoam sponge. An animal model of acute renal damage was established in 1 months. The atrial fibrillation model was established in the right atrium by 3H in the simple pacing group and the 5 kidney damage animal models. The renal function, the degree of renal damage and the induced atrial fibrillation before and after the stimulation of the renal embolism group were compared. The endothelial work in the simple pacing group and the animal model group was compared. Energy, coagulation index, inflammation and oxidative stress, renin angiotensin aldosterone system activity. Second: experimental animals were randomly assigned to model group (n=10), simple pacing group (n=5) and blank control group (n=5), in which the simple pacing group and the blank control group were the first part. The unilateral renal artery was embolized by gelatin sponge. An animal model of chronic renal damage was established for 3 months. Simple pacing group and 5 kidney damage animal models were used to stimulate 3H to establish atrial fibrillation model in the right atrium. The renal function, the degree of renal damage and the induced atrial fibrillation before and after the stimulation of the renal embolism group were compared. The simple pacing group and the 1 month animal model were compared. The endothelial function, coagulation index, inflammation and oxidative stress, and renin angiotensin aldosterone system activity in the group and 3 month animal model group. Results the first part: acute renal ischemic damage combined with moderate renal insufficiency in 1 months of embolized unilateral renal artery. The right atrial rapid stimulation of 3H can establish the model of atrial fibrillation. After 1 months of dirty damage, the rapid stimulation of the experimental animal and the right atrium could have the following changes: (1) the atrial refractory period and the VVF point of atrioventricular node shortened; (2) the increase of atrial fibrillation induced rate; (3) the acute renal insufficiency with atrial fibrillation compared with the atrial fibrillation group, the endothelial function was lighter, the prothrombin substance decreased, the fibrinolysis system was enhanced, inflammation and oxidative stress reaction The second part: the second part of the main trunk of the renal artery embolization for 3 months can cause chronic renal ischemic damage and moderate renal insufficiency. The right atrium stimulates rapid stimulation of the atrial fibrillation model. After 3 months of renal damage, the following changes can occur after the rapid stimulation of the experimental animal and the right atrium: (1) the atrial refractory period and the atrioventricular node Venter's point shortening; 2) the increase of atrial fibrillation induced rate; (3) chronic renal failure with atrial fibrillation than atrial fibrillation group with severe endothelial dysfunction, increased procoagulant substances, fibrinolysis, strong inflammatory reaction, RAAS system activation. (4) chronic renal insufficiency with atrial fibrillation more acute renal dysfunction accompanied by atrial fibrillation internal function damage, procoagulant substance increase, fibrinolysis hypofunction, inflammation Symptoms, oxidative stress reaction and RAAS system activation. Conclusion 1. successful establishment of acute and chronic renal damage combined with moderate renal dysfunction large animal model, and on the basis of the successful establishment of atrial fibrillation model.2. application of the animal model, acute renal damage combined with moderate renal dysfunction with atrial fibrillation endothelial dysfunction is lighter, the body out of the body. The risk of blood loss is high, and the risk of thrombosis is small..3. chronic renal damage combined with moderate renal insufficiency with atrial fibrillation has serious endothelial dysfunction, thrombosis risk and bleeding risk.
【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】：2016
【分类号】：R692;R541.75

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