全脑常规照射对血脑屏障功能影响的实验研究

目的 探讨全脑常规照射对大鼠血脑屏障(BBB)功能的影响。方法 采用⁶⁰Coγ射线对SD大鼠进行不同剂量的全脑常规外照射,照射后16 h,静脉给予甲氨蝶呤(MTX)后监测血液及脑脊液(CSF)中的MTX浓度;同时镧示踪法电镜观察大鼠新鲜脑组织标本。结果 1 CSF中MTX浓度在10 Gy组与对照组、30与40 Gy组比较差异无统计学意义(P>0.05),其余各组间比较差异均有统计学意义(P<0.05)。2对照组镧颗粒仅局限分布在血管腔内;10 Gy组紧密连接处见镧颗粒沉积;20 Gy组镧颗粒弥漫性地分布于神经细胞间隙;30 Gy组镧颗粒进入神经细胞内,并分布于线粒体、内质网等细胞器的表面;40 Gy组镧颗粒弥漫分布于脑组织细胞间和细胞内,可见毛细血管内皮细胞及神经细胞失去正常形态,结构破坏。结论 放射线具有增加BBB通透性的作用;照射30 Gy后BBB通透性达最高,提示全脑常规照射30 Gy后可能为最佳化疗时机;40 Gy后不宜继续进行全脑照射,否则会导致不可逆性放射性脑损伤的发生,对临床治疗可能有指导意义。

Experimental study of conventional whole-brain irradiation on the function of blood-brain barrier

Objective To explore the effect of conventional whole-brain radiation therapy(WBRT)on the blood-brain barrier (BBB) in rats and provide the experimental basis for the optimum time of clinical chemotherapv after conventional WBRT.Methods 100 Sprague-Dowley rats were randomly divided into five groups,normal control group,10 Gy group,20 Gy group,30 Gy group and 40 Gy group.The rats were exposed to conventional fractionation(2 Gy/day,5 days a week)for a total dose of 10-40 Gy with 60Co γ-rays.MTX(25 ms/kg body weight)were injected intravenously 16 h after each group finished the planned irradiation dosage, and the CSF and blood samples were collected 2 hours later.MTX levels in samples were measured by using RP- HPLC.The changes of ultrastructure of BBB in 4 rats of each group were observed using lanthanum trace labeling with electron microscopy.Results The average concentrations of MTX in rat's CSF in control group,10 Gy group.20 Gy group,30 Gy group and 40 Gy group were 0.068,0.078,0.118,0.236 and 0.229 ms/L, respectively.The MTX concentration in CSF was increasing but not statistically different between the control group and 10 Gy group(P>0.5),so was between the 30 Gy group and 40 Gy group(P>0.5).The MTX concentration difference in CSF between any other two groups was statistically significant(P<0.05).The lanthanum was only seen in the lumens of capillaries but not in the extravessels on the control rats.The lanthanum entered the outside of capillaries but not in the extravesscls in 10 Gy group.It entered the extra cellular space but not the neurons in 20 Gy group,and the plasma, mitochondria and endoplasmic reticulum of neurons in 30 Gy group.For 40 Gy group,lanthanum nitrate particles were observed in the brain tissue diffusely, and a few endothelial cells and neurons lost normal configuration.Conclusions Radiation could directly damage the function and structure of BBB,and the penetration of BBB reaches the peak at 30 Gy,which suggests that it may be a best chemotherapy opportunity after 30 Gy.The limit dose of whole brain radiotherapy is 40 gray,otherwise it may cause irreversible brain injure.