丁苯酞对放射性脑损伤大鼠血脑屏障的影响

doi:10.3760/cma.j.issn.1004-4221.2012.04.028

摘要
图/表
参考文献()
相关文章 (2)
点击分布统计
下载分布统计

全文: PDF (0 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的观察大鼠单次全脑照射后血脑屏障改变和丁苯酞的干预作用,探讨其对放射性脑损伤的防护作用机制。方法 144只SD大鼠随机分为空白对照组、单纯照射组、单纯丁苯酞组、丁苯酞联合照射组。照射采用4 MV X线单次10 Gy全脑照射,丁苯酞分别按0.3、1.0、3.0 mg/kg腹腔注射。测定脑组织依文思蓝(EB)含量,免疫组化法分析脑组织血管内皮生长因子(VEGF)表达,心脏取血计数循环内皮细胞(CEC)数,用MRI观察T₁、T₂加权信号强度以及信号强度增强率。组间比较采用方差分析中的Student-Newman-Keuls检验。结果与空白对照组比较,单纯照射组大鼠脑组织EB含量、VEGF表达、CEC数明显增高\[2.81∶7.82(P=0.002)、5.83∶10.26(P=0.003)、3.16∶6.14(P=0.002)\],T₁加权信号强度降低(P=0.004~0.018),T₂加权信号强度及信号强度增强率升高(P=0.007~0.036)。与单纯照射组比较,丁苯酞联合照射组大鼠脑组织EB含量、VEGF表达、CEC数均降低\[7.80∶3.86(P=0.007)、10.83∶5.26(P=0.008)、6.36∶3.64(P=0.009)\],T₁、T₂加权信号强度及信号强度增强率改变均降低(P=0.008~0.026、0.006~0.038)。结论丁苯酞通过降低大鼠全脑照射后脑组织VEGF表达、CEC数来降低血脑屏障通透性。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	陈应柱
	张娴娴
	肖璐
	戚艳红
	杨璞
	田野
	包仕尧

关键词 ：血脑屏障, 辐射防护, 丁苯酞

Abstract：Objective To investigate the effects of 1-3-n-Butylphthalide on the blood-brain barrier (BBB) following whole brain irradiation in rats. Methods 144 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. Results Compared 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.

Key words： Blood-brain barrier Radiation protection 1-3-n-Butylphthalide

收稿日期: 2011-08-13

基金资助:江苏省卫生厅重大科研课题(K200406)

引用本文:

陈应柱,张娴娴,肖璐等. 丁苯酞对放射性脑损伤大鼠血脑屏障的影响[J]. 中华放射肿瘤学杂志, 2012, 21(4): 392-395.

CHEN Ying-zhu^*,ZHANG Xian-xian,XIAO Lu et al. Effects of 1-3-n-Butylphthalide on the blood-brain barrier following whole brain irradiation in rats[J]. Chinese Journal of Radiation Oncology, 2012, 21(4): 392-395.

链接本文:

http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.issn.1004-4221.2012.04.028 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2012/V21/I4/392

[1] Romero AA, Gross SR, Cheng KY, et al. An age-related increasein resistance to DNA damage-induced apoptotic cell death is associated with development of DNA repair mechanisms. J Neurochem,2003,84:1275-1287.
[2] 赵嘉,李玲,裴中,等.丁苯酞对缺血性脑损伤作用的细胞靶点研究.中国卒中杂志,2010,5:119-125.
[3] 田野,包仕尧,殷蔚伯.大鼠半脑照射后早期脑内血流量和含水量变化的研究.中华放射肿瘤学杂志,1999,8:43-46.
[4] Hladovec J. Circulating endothelial cells isolated together with platelet and the experimental modification of their counts in rats. Thromb Res,1973,3:665-764.
[5] Morimoto N, Ebara M, Kato H, et al. Early detection of radiation-induced liver injury in rat by superaramagnetic iron oxide-enhanced MR imaging. J Magn Reson Imaging,1999,9:573-578.
[6] O′Connor MM, Mayberg MR. Effects of radiation on cerebral vasculature:a review. Neurosurgery,2000,46:138-151.
[7] Kaya M, Gulturk S, Elmas L,et al. The effects of magnesium sulfate on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats. Life Sciences,2004,26:201-212.
[8] Kim JH, Chung YG, Kim Y, et al. Upregulation of VEGF and FGF2 in normal rat brain after experimental intraoperative radiation thearpy. J Korean Med Sci,2004,19:879-886.
[9] Butthep P, Rummavas S, Wisedpanichkij R, et al. Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemial. Am Hematol,2002,70:100-106.
[10] Chong AY, Lip GY, Freestone B, et al. Increased circulating endothelial cells in actute heart failure:comparison with von Willebrand factor and soluble E-selection. Eur J Heart Fail,2006,8:167-172.
[11] Harria NG, Gauden V, Fraser PA, et al. MRI measurement of blood-brain barrier permeability following spontaneous reperfusion in the starch microsphere model of ischemia. Magn Reson Imaging,2002,20:221-230.
[12] Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev,2005,57:173-185.
[13] Guo S, Kim WJ, Lok J, et al. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci USA,2008,105:7582-7587.
[14] Peng Y, Xu S, Chen G, et al. 1-3-n-Butylphthalide improves cognitive impairment induced by chronic cerebral hypoperfusion in rats. J Pharmacol Exp Ther,2007,321:902-910.
[15] 施晓耕,黄如训,刘春岭,等.丁苯酞对高血压性脑卒中预防作用的实验研究.中国神经精神疾病杂志,2007,33:486-489.