全颅放疗对大鼠血脑屏障LRP和P-gp表达的影响及临床意义

Impact of Expression and Significance of Lung Resistance-related Protein, P-glycoprotein at Blood-brain Barrier after Whole Brain Conventional Fractionation Irradiation in Rats

目的探讨不同剂量放射线对大鼠血脑屏障上肺耐药相关蛋白(LRP)、多药耐药蛋白(P-gp)表达的影响影响及其其临床意义。方法将50只成熟雄性Wister大鼠随机分为5组,分别采用0,10,20,30,40Gy60Coγ射线进行全脑常规分割外照射,1次/d,2Gy/次,5次/周。于完成预定照射剂量后16h断头取脑,采用免疫组化法检测各组大鼠血脑屏障上LRP和P-gp的表达情况。结果 0Gy组LRP和P-gp表达均较强,随着照射剂量的增加,LRP表达呈现逐渐下降趋势,其中20Gy下降最明显,30,40Gy组下降幅度减弱,40Gy时表达最弱。20,30,40Gy组和对照组比较差异有显著性;10Gy组与20,20,30,40Gy组比较差异有显著性;其余各组比较无统计学差异。P-gp的表达也随着照射剂量的增加呈现减弱的趋势,20Gy降低幅度最大,30Gy时达到最低值,40Gy时略增强。对照组分别与20,30,40Gy组相比较,差异有显著性;10Gy组与20,30,40Gy组比较,差异有显著性;其余各组比较无差异。结论一定剂量的放射线作用于大鼠血脑屏障之后,其上的耐药相关蛋白表达均可降低,20Gy时降低最明显,此时配合化疗药物效果最佳。

Objective To explore the effect of expression of LRP and P-gp at blood-brain barrier after different doses of whole brain conventional fraction irradiation in rats. Methods According to different irradiation doses, 50 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 γ-ray. All rats were killed and collected brain 16 hours after whole brain irradialion and detected expression of LRP, P-gp at BBB by SP immunohistochemistry. Result LRP and P-gp was hign expression in normal BBB. With the increase of radiation dose, expression of LRP and P-gp decreased to varying degree. The positive cells of P-gp were lowest in 30Gy group. The positive cells of LRP were lowest 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. Conclusion A certain dose irradiation can decrease expression of LRP and P-gp. It can be considered as the optimum time of chemotherapy when the whole brain irradiation ranges from 20Gy to 30Gy.