布美他尼与光动力疗法联合应用对大鼠C6胶质瘤的治疗作用

目的：探讨布美他尼对PDT诱导加剧的大鼠C6胶质瘤瘤周水肿的治疗作用。方法：培养C6胶质瘤细胞,建立C6大鼠胶质瘤模型,分成：A：空白对照组,B：光动力治疗组,C：布美他尼治疗组,D：光动力和布美他尼联合治疗组。荷瘤21天后取材测量瘤重,瘤周水含量,微血管密度,NKCC-1和ZO-1的表达。另外MRI监测肿瘤生长,记录大鼠生存时间。结果：PDT能够抑制胶质瘤细胞生长增殖,杀伤肿瘤细胞,促使肿瘤细胞凋亡,下调紧密连接相关蛋白的表达来打开紧密连接,从而延长生存期,同时诱使NKCC-1过表达引起瘤周水肿加剧。结论：应用布美他尼联合治疗能抑制PDT单独应用引起的NKCC-1过表达,减轻PDT加重的瘤周水肿,增强PDT的杀肿瘤作用,而不减少ZO-1的表达。

The Effect of Bumetanide Combined with Photodynamic Therapy on Rat C6 Glioma

Objective： To investigate the effect of bumetanide on peri-tumor edema caused by photodynamic therapy（PDT） of intraparenchymal C6 glioma xenografts. Methods： Seven days after inoculation with C6 cells,rats with MRIconfirmed glioma received PDT,injection of bumetanide or a combination of the two treatments. After treatment,tumor volume,tumor weight,brain water content,microvessel density,expression of NKCC-1,ZO-1 and animal survival time were examined. Results： In the PDT group,tumor growth was significantly inhibited and survival prolonged. Bumetanide enhanced the efficacy of PDT and reduced PDT-induced peri-tumor edema in the combined PDT ＋ bumetanide treatment group where NKCC-1 expression in response to PDT was significantly suppressed. ZO-1 expression was significantly suppressed in the PDT-only group. This suppression was not observed in the combined PDT ＋ bumetanide treatment group.Conclusion： PDT,in combination with bumetanide was observed to significantly inhibit the growth of C6 glioma,relieve peri-tumor edema caused by PDT alone and prolongsurvival. These results suggest that PDT,in combination with bumetanide,may be a useful and promising strategy in the treatment of human glioma.peri-tumor edema caused by PDT alone and prolongsurvival. These results suggest that PDT, in combination with bumet- anide, may be a useful and promising strategy in the treatment of human glioma.