建立椎管内静脉高压动物模型的手术方法及稳定性评价*

背景：构建稳定的脊髓静脉高压动物模型可为临床研究脊髓血管病变提供可靠的平台，课题组前期已成功构建了兔脊髓静脉高压模型。 目的：在前期研究基础上改进手术方法和围手术期处理，建立长期稳定的兔脊髓静脉高压模型。 方法：48只新西兰大白兔随机分为急性期组、短期组、中期组、长期组，每组12只兔又分为模型兔8只和假手术兔4只。模型兔通过开腹侧侧吻合兔左肾动静脉，形成动静脉瘘，结扎后腔静脉远端和近端导致动脉血异常引流至腰静脉、椎管内静脉丛形成脊髓淤血和脊髓静脉高压。采用Jacobs法对后肢功能评级，Reuter法评估脊髓感觉运动反射功能，每组动物到期后对模型兔行MRI扫描、经股动脉DSA检查动静脉瘘口的通畅，并灌注解剖取脊髓行病理学检查以判定模型符合要求。 结果与结论：32只模型兔存活29只，生存率91%，动静脉瘘口通畅率79%，但长期组瘘口通畅率低，仅29%。术后模型后肢运动、感觉功能均有所减退。模型兔脊髓MRI表现为脊髓相应阶段的水肿；病理检查在光镜下见脊髓实质内淋巴细胞的浸润、胶质细胞的增生、髓内血管的玻璃样变性和神经元细胞变性，符合脊髓静脉高压的脊髓病理变化；透射电镜观察可见髓鞘板层的松散、薄髓纤维内线粒体数目增加和神经元的固缩。提示成功建立模拟人类脊髓血管畸形的脊髓静脉高压机制导致脊髓损伤的动物模型，该模型的可靠性和稳定性较高。

Surgical method and stability evaluation to establish animal models of intraspinal venous hypertension

BACKGROUND: A stable spinal cord venous hypertension model can provide a reliable platform for studying spinal cord vessel lesions. Our pre-test has constructed rabbit models with intraspinal venous hypertension successfully. OBJECTIVE: To improve surgical methods and perioperative nursing for a long-term stable model of spinal cord venous hypertension in rabbits. METHODS: Totally 48 rabbits were randomly divided into four groups: acute, short-term, mid-half, and long-term. Eight rabbits in each group were divided into model group and 4 rabbits for sham-sugery group. The model rabbits were arteriovenous fistulas by side to side anastomosis between left renal artery and vein. The distal end of the inferior vena cave as well as its proximal end was ligated, in order to make the arterial blood stream drains anomalously to lumbar veins and internal vertebral veins, resulting in spinal cord congestion and spinal cord venous hypertension. The grade of hind limb function was assayed with Jacobs method, and the kinetic, sensory function of spinal reflex was scored with Reuter method, then observed the rabbits behavior changes continuously. MRI and DSA from femoral artery were performed among rabbit models in each group on time to check the arteriovenous fistulas, and then the animals were sacrificed after perfusion and the spinal cord was removed for histopathologic study. RESULTS AND CONCLUSION: Of the 32 animals in the model group, 29 survived. The survival rates were 91%. The patency rates were 79%, but it was lower in long-term group (29%). The kinetic, sensory function of hind limb decreased after operation. MRI showed that there were spinal cord edemas at the corresponding stage. Under light microscopy, the pathological features of spinal cord hypertension were marked capillary expansion and congestion within the spinal cord, perivascular lymphocyte infiltration, Gliosis, hyalinized vascular in spinal cord, neurons cellular degeneration from time to time. Myelin sheath layers loose, the number of mitochondria increased within thin-myelinated fibers and pycnosis neurons could be seen by the transmission electron microscope. It is revealed we establish an animal model of spinal cord injury caused by spinal cord venous hypertension, which simulated spinal cord vascular malformation of human.