肾血管性高血压大鼠模型的建立和评测

背景:建立一种有效并简便可靠的高血压动物模型,对研究高血压的机制和治疗有重要的意义。目前,国内外常利用犬、大鼠、兔等实验制作高血压动物模型,其中肾动脉狭窄性高血压模型由于简便可靠被广泛应用于人类高血压及其并发症的研究。目的:建立简便、可靠的大鼠实验性肾动脉狭窄性高血压模型。设计:随机分组设计、动物实验。单位:青岛大学医学院附属医院脑血管病研究所。材料:实验于2005-09/2006-02在山东省脑病防治重点实验室完成。选择健康Wistar大鼠81只,随机数字表法分为单侧肾动脉狭窄组18只,双侧肾动脉狭窄组17只,单侧肾动脉结扎组15只,双侧肾动脉结扎组15只,单侧肾动脉狭窄假手术组6只,双侧肾动脉狭窄假手术组4只,正常对照组6只。方法:单侧肾动脉狭窄组,微型银夹夹闭右侧肾动脉,12d后手术切除左侧肾脏。双侧肾动脉狭窄组,微型银夹夹闭右侧肾动脉,12d后左侧做同样处理。单侧肾动脉结扎组,丝线结扎右侧肾动脉,12d后手术切除左侧肾脏。双侧肾动脉结扎组,丝线结扎右侧肾动脉,12d后左侧做同样处理。单侧肾动脉狭窄假手术组,手术暴露右侧肾脏,不做处理放回原位。12d后切除左侧肾脏。双侧肾动脉狭窄假手术组,手术暴露右侧肾脏,不做处理放回原位,12d后左侧做同样处理。正常对照组6只,不作任何处理。应用RBP-2大鼠血压计测量鼠尾血压和心率。主要观察指标:造模成功率、大鼠血压、心率。结果:纳入动物81只,死亡61只,均进入结果分析。①血压:单侧肾动脉狭窄组、双侧肾动脉狭窄组、双侧肾动脉结扎组血压明显高于正常对照组、双侧肾动脉狭窄假手术组[分别为(138.0±36.5),(154.2±11.6),(160.5±0.7),(101.3±17.6),(108.3±5.7)mmHg]。②心率:各肾动脉狭窄组动物心率变化不稳定,单侧肾动脉狭窄组、双侧肾动脉狭窄组、双侧肾动脉结扎组、正常对照组、双侧肾动脉狭窄假手术组分别为[(367.5±47.2),(420.2±47.8),(386.0±4.2),(390.3±42.4),(417.3±27.5)次/min]。③存活率:肾动脉狭窄组存活率(单侧22%,双侧29%)显著高于肾动脉结扎组(单侧0,双侧12%),以双侧肾动脉狭窄组存活率最高。结论:双侧肾动脉夹闭法可建立稳定的肾动脉狭窄性高血压大鼠模型。

Establishment and evaluation of renovascular hypertensive rat models

BACKGROUND: It is significant to establish a kind of effective, conve nient and reliable animal model of hypertension. At present, dogs, rats and rabbits are usually used to establish hypertensive models at home and abroad, and the renal artery stenosis induced hypertensive models are ex tensively used to research hypertension and its complication for human be ings because they are convenient and reliable, and there are many methods to establish them, but the effects are to be evaluated. OBJECTIVE: To establish convenient and reliable animal models of ex perimental renal artery stenosis induced hypertension. DESIGN: A randomized grouping design and animal experiment. SETTING: Institute of Cerebrovascular diseases, Medical College Hospital of Qingdao University. MATERIALS: The experiments were carried out in Shandong Key Labora tory for Prevention and treatment of Brain Disease from September 2005 to February 2006. Eighty-one healthy Wistar rats divided into 7 groups accord ing to the method of random number table: unilateral renal artery stenosis group (n=18), bilateral renal artery stenosis group (n=17), unilateral renal artery ligation group (n=15), bilateral renal artery ligation group (n=15), uni lateral renal artery stenosis sham-operated group (n=6), bilateral renal artery stenosis sham-operated group (n=4) and normal control group (n=6). METHODS: Unilateral renal artery stenosis group: Right renal artery was clamped with miniature silver clip, and left kidney was resected after 12 days. Bilateral renal artery stenosis group: Right renal artery was clamped with miniature silver clip, and the same treatment was given to the left side after 12 days. Unilateral renal artery ligation group: Right renal artery was ligated with filament, and left kidney was resected after 12 days. Bilateral renal artery ligation group: Right renal artery was ligated with filament, and the same treatment was given to the left side after 12 days. Unilateral renal artery stenosis sham-operated group: Right kidney was exposed, and returned to the original place without any treatment, and left kidney was resected af ter 12 days. Bilateral renal artery stenosis sham-operated group: Right kid ney was exposed, and returned to the original place without any treatment, and the same treatment was given to the left side after 12 days. Normal con trol group: The rats were not given any treatment. The blood pressure and heart rate were determined with RBP-2 hemomanometer for rats. MAIN OUTCOME MEASURES: The successful rate of model estab lishment, blood pressure and heart rate were observed. RESULTS: Totally 81 rats were used, and 61 of them died, all were in volved in the analysis of results without deletion. ① Blood pressures in the unilateral and bilateral renal artery stenosis groups and bilateral renal artery ligation group were obviously higher than those in the normal control group and bilateral renal artery stenosis sham-operated group [(138.0 ±36.5), (154.2±11.6), (160.5±0.7), (101.3±17.6), (108.3±5.7) mm Hg]. ② The changes of heart rate in the renal artery stenosis group were unstable, and the heart rates in the unilateral and bilateral renal artery stenosis groups, bilateral renal artery ligation group, normal control group and bilat eral renal artery stenosis sham-operated group were (367.5±47.2), (420.2 ±47.8), (386.0±4.2), (390.3±42.4), (417.3±27.5) beats per minute, respec tively. ③ The survival rates in the renal artery stenosis groups (22%, 29%) were significantly higher than those in the renal artery ligation groups (0,12%), and it was the highest in the unilateral renal artery stenosis group.CONCLUSION: The method of clamping bilateral renal arteries can establish stable rat models of hypertension induced by renal artery stenosis.