Regulatory effect of vascular endothelial growth factor on blood spinal cord barrier in presyrinx state of experimental syringomyelia

摘要

BACKGROUND:Vascular endothelial growth factor (VEGF) is able to regulate blood spinal cord barrier function as well as influence neovascularization and cause edema. OBJECTIVE: Through establishment of a rabbit model of syringomyelia,to explore the correlation between VEGF protein and mRNA expressions and function of blood spinal cord barrier and edema degree of spinal cord in presyrinx state. DESIGN,TIME AND SETTING: Randomized controlled animal study was performed in the Tumor Institute of the Fourth Hospital,Hebei Medical University from January to June 2007. MATERIALS: A total of 0.6 mL Kaolin solution (250 g/L,37 ℃) was injected into the cisterna magna of 40 rabbits in the kaolin group to establish syringomyelia models. Goat anti-rabbit VEGF monoclonal antibody was provided by DIACLONE Company,USA; RT-PCR related reagents were provided by Huamei Bioengineering Co.,Ltd.,Beijing. METHODS: Sixty Chinese white rabbits were divided randomly into two groups: Kaolin group (n=40) and control group (n=20). Physiological saline (0.6 mL at 37 ℃) was injected in rabbits of control group. On days 1,3,7,14 and 21 after kaolin injection,cervical cords samples were harvested after sacrifice of animal. MAIN OUTCOME MEASURES: VEGF protein and mRNA expressions were detected by immunohistochemistry and RT-PCR on days 1,3,7,14,and 21 after kaolin injection. A quantitative analysis of blood spinal cord barrier function was performed by Evans blue technique. Water content of the spinal cord was measured by dry-wet weight technique. The correlation between the expression of VEGF protein and mRNA and the function of blood spinal cord barrier in the upper cervical cord of the presyrinx state was analyzed by linear correlation analysis. RESULTS: The water content and Evans blue content increased in the kaolin group on days 1 and 3 postoperatively compared with the control group (F=7.387,61.35,P<0.05,0.01),and reached a peak on day 7 (F=135.94,528.35,P<0.01). They declined slowly to day 21 postoperatively,but both contents were still higher than the control group (F=11.51,58.63,P<0.01). VEGF protein expression increased on day 1,and stronger positive expression was seen on days 3,7 and 14. It decreased on day 21. VEGF protein expression was higher than the control group at each time point (F=137.4-468.5,P<0.01). VEGF mRNA expression showed the same pattern in the cervical cord at different time points. By statistical analysis,the expression of VEGF protein and mRNA had a significantly positive correlation with the structural and functional changes of the blood spinal cord barrier in the presyrinx state (r=0.604-0.979,P<0.05). CONCLUSION: In the presyrinx state of syringomyelia,the expressions of VEGF protein and mRNA can influence the structure and function of the blood spinal cord barrier and play an important role in the formation and development of spinal cord edema and syringomyelia.