Effects of 1-3-n-Butylphthalide on the blood-brain barrier following whole brain irradiation in rats / 中华放射肿瘤学杂志

ABSTRACT

ObjectiveTo investigate the effects of 1-3-n-Butylphthalide on the blood-brain barrier (BBB) following whole brain irradiation in rats.Methods144 male Sprague Dawley rats were randomly divided into sham-irradiation group,irradiation group,1-3-n-Butylphthalide group,and irradiation plus 1-3-n-Butylphthalide group.Whole-brain irradiation was given as a single-dose of 10 Gy using 4 MV X-ray.The rats were injected intraperitoneally with 1-3-n-Butylphthalide at 0.3 mg/kg,1.0 mg/kg,3.0 mg/kg once per day.The changes of the BBB were assessed by Evans blue (EB) assay.The expression of vascular endothelial growth factor (VEGF) in the brain tissue was determined by immunohistochemistry. The circulating endothelial cells (CECs) isolated from right ventricular blood were counted.MRI was evaluated with the T1-weighted images,T2-weighted images and MRI enhancement images induced by Gd-DTPA.The data were compared among the groups through Student-Newman-Keuls test.ResultsCompared with the sham-irradiation group,the EB content,the expression of VEGF in the brain tissue and the CECs were significantly increased in the irradiation group (2.81∶ 7.82,P =0.002;5.83∶ 10.26,P=0.003;3.16∶6.14,P =0.002).The signal intensity of T1-weighted images was significantly decreased while T2-weighted images and the enhancement rate significantly increased in the irradiation group (P =0.004 -0.018 ).Compared with irradiation group,the EB content,the expression of VEGF and the CECs were decreased significantly in the irradiation plus 1-3-n-Butylphthalide group ( 7.80∶ 3.86,P =0.007 ; 10.83 ∶ 5.26,P =0.008 ;6.36∶ 3.64,P =0.009 ).However,the changes in the MRI were significantly attenuated ( P =0.008-0.026,and 0.006 -0.038,respectively).Conclusions Following whole brain irradiation,1-3-n-Butylphthalide can decrease the permeability of the BBB in rats via decreasing VEGF expression and decreasing the CECs.