脊髓静脉高压兔模型的初步建立

Preliminary establishment of an rabbits model of spinal cord venous hypertension

目的建立脊髓静脉高压的兔模型,用于脊髓血管畸形发病机制的研究。方法取新西兰白兔22只,分为实验组18只,正常对照组4只。对实验组兔行左侧肾动静脉的端-侧吻合,构建动静脉瘘。结扎左侧肾动静脉的肾门端,在左、右肾静脉之间结扎下腔静脉的近心端,在降结肠静脉以近结扎下腔静脉的远心端,使左侧肾动脉的血流经动静脉瘘口进入下腔静脉,再经腰静脉返流到椎旁静脉丛,继而逆流入硬脊膜内的脊髓冠状静脉丛,造成脊髓静脉高压环境。术后1、3、7、14d及以后每周评价兔的双侧后肢运动、感觉功能(共计5周)。实验组术后分为早(≤3d)、中(4d至3周)、晚(>3周)3期,从存活的每期兔中随机抽取2只,经股动脉行腹主动脉造影,了解瘘口通畅及血流情况;行磁共振扫描,观察脊髓的影像学改变;行病理学检查,观察脊髓组织结构的变化。正常对照组只麻醉,不实施手术,抽取2只行MRI和病理检查,作为与模型组对照的基准。结果实验组18只兔中,死亡5只,存活13只。与术前相比,术后实验组兔的运动和感觉功能均有所下降,术前兔的运动功能评分为4.0±0.0,术后分别为:第3天3.1±0.5,第2周2.6±0.5,第4周2.9±0.8;术前感觉功能评分为0.0±0.0,术后分别为:第3天4.9±1.7,第2周6.3±1.6,第4周5.4±2.6。造影显示实验组抽取的6只兔中,早期2只兔瘘口均通畅;中期1只瘘口存在,1只部分闭塞;晚期2只瘘口均闭塞。与正常对照组相比MRI显示,瘘口通畅的实验组兔,胸腰段脊髓异常信号,病理检查显示,脊髓实质淤血,但水肿及变性坏死不明显。结论本研究建立的动物模型能够模拟人脊髓静脉高压的病理生理学过程,但模型的长期稳定性需要进一步观察。

Objective To establish an rabbits model of spinal cord venous hypertension for the research of pathophysiology in spinal cord vascular malformations. Methods Twenty-two New Zealand albino rabbits were randomly divided into experimental （n = 18 ） and normal control （n = 4） groups. Arteriovenous fistula was constructed with the left renal arteriovenous end-to-side anastomosis. The end of left renal arteriovenous renal hilum was ligated. The proximal end of inferior vena cava was ligated between left and right renal veins; the distal end of inferior vena cava was ligated proximal to descending colonic vein. The blood from left renal artery flowed into inferior vena cava through the arteriovenous fistula, refluxed into the paraspinal venous plexus through the lumbar vein, and then refluxed into the intradural spinal cord coronary venous plexus, which causing the venous hypertension in spinal cord. Hindlimb motor and sensory function of the rabbits were evaluated on day 1, 3, 7 and following each week after the operation. The model rabbits were divided into early, medium and terminal stage group. 2 rabbits were randomly selected from each group for abdominal aortography, spinal cord MRI, and pathological examination of spinal cord. Results Of the 18 model rabbits operated, 5 died, and 13 survived. Compared with preoperative function score, the motor and sensory function of spinal cord deteriorated in model rabbits. The mean of preoperative motor score was 4.0 ±0.0,and the postoperative was as following： 3rd day 3.1 ±0. 5,2nd week 2.6 ±0. 5, 4th week 2.9 ± 0. 8;The mean of preoperative sensory score was 0. 0 ± 0. 0, and the postoperative was as following： 3rd day 4. 9 ± 1.7, 2nd week 6. 3 ± 1.6,4th week 5.4 ± 2. 6. Among the 6 selected model rabbits, fistulas of 2 rabbits in early stage and 1 in medium stage were patent, and 1 in medium stage was partially occluded, 2 in terminal stage were occluded totally. Thoracolumbar spinal cord MRI showed abnormal signals in fistula patent models, and pathological examination showed congestion in spinal cord parenchyma, but edema and degeneration/necrosis were not significant. Conclusion This animal model may simulate the pathophysiological processes of human spinal cord venous hypertension, however, the long-term stability of the model needs to be further studied.