全颅常规外照射对大鼠血脑屏障通透性的影响及相关机制研究  

Impact of drug permeability of blood-brain barrier and related mechanism after whole brain conventional fractionation irradiation in rats

作　　者：齐彩霞[1] 

机构地区：[1]山西大同大学医学院诊断学教研室,山西大同037009

出　　处：《青岛医药卫生》2013年第1期37-40,共4页Qingdao Medical Journal

摘　　要：目的探讨全颅常规外照射增加大鼠血脑屏障药物通透性的产生机制,为临床对颅内肿瘤寻找合适的化疗时机提供理论依据。方法 60只正常成年Wistar大鼠随机分为5组,分别采用0、10、20、30、40Gy,60Coγ射线进行全脑常规分割外照射,2Gy/次、1野/次,5次/周。各组完成照射计划后16h经尾静脉注射氨甲喋呤(MTX)25mg/kg,2h后采集脑脊液,用RP-HPLC法检测其中的MTX浓度。之后所有大鼠均断头取脑,40g/L中性甲醛固定24h,石蜡包埋,采用免疫组化法检测各组大鼠血脑屏障上P-gp的表达情况。结果对照组P-gp阳性表达最强,10Gy组与对照组,20Gy与30Gy组,40Gy组分别与20Gy、30Gy组比较无统计学意义(P>0.05),其余各组比较均有统计学意义(P<0.05)。各组大鼠脑脊液中的MTX平均浓度分别为:0.06、0.08、0.19、0.24、0.23mg/L。经方差分析及秩和检验,10Gy组与对照组,20Gy与30Gy组,40Gy组分别与20Gy、30Gy组比较无统计学意义(P>0.05),其余各组比较均有统计学意义(P<0.05)。结论一定剂量的放射线可能通过降低血脑屏障上P-gp的表达,增加其对药物的通透性,并且在放射剂量达到20Gy的时候化疗效果最好。Objective To explore the effect of drug permeability in rat blood-brain barrier after different doses of whole brain conventional fraction irradiation in rats and provide the experimental basis for optimum time of clinical chemotherapy. Methods According to different irradiation doses, 60 adult male Wistar rats were divided randomly into 5 groups： the normal control group（0Gy） ;10Gy; 20Gy; 30Gy; 40Gy group. All rats were exposed to conventional fravtionation （2Gy/d,5d/w） with 6~CoT-ray. MTX（25mg/kg） was injected through the tail mainline 16 hours after whole brain irradiation. Cerebrospinal fluid（CSF） was collected 2 hours later. Those samples were used to assay MTX concentration using RP-HPLC. All rats were killed and collected brain, detected expression of P-gp at BBB by SP immunohistochemistry. Results P-gp was high expres- sion in normal BBB. With the increase of radiation dose, expression of P-gp decreased to varying degree. The positive cells of P-gp were lowest in 30Gy group,it was enhanced in some extent in 40Gy group. All the date was analyzed with rank test of transform. The positive cells was significantly different except the control and 10Gy, 20Gy and 30Gy, 20Gy and 40Gy, 30Gy and 40Gy. MTX mean concentration. In CSF was 0. 06,0. 08,0.19,0. 24,0. 23mg/L in the control, 10Gy,20 Gy,30 Gy,40 Gy groups,respectively. All the dates was analyzed with rank test of transform, MTX concentration of CSF was significantly different except the control and 10Gy, 20 Gy and 30 Gy group, 30 Gy and 40 Gy group. Conclusion A certain dose irradiation can decrease the expression of P-gp, then increase drug permeability of blood-brain barrier. The positive cells are markedly decreased from 20Gy to 30Gy. It can be considered as the optimum time of chemotherapy when the whole brain irradiation ranges from 20Gy to 30Gy.

关 键 词：血脑屏障 放射疗法 颅脑 氨甲喋呤 P-GP 

分 类 号：R73-33[医药卫生—肿瘤]