HBO联合尼莫司汀治疗脑胶质瘤裸小鼠模型的研究

Hyperbaric oxygen therapy sensitizes chemotherapy in human glioma- bearing nude mice

目的探讨高压氧(hyperbaric oxygen,HBO)联合化疗药物治疗脑胶质瘤裸小鼠模型中的增敏效应。方法将鼠间传代胶质瘤组织块接种于裸小鼠皮下后第3天将其随机分为对照组(n=10)、HBO组(n=5)、尼莫司汀(nimustine,ACNU)组(n=5)、ACNU+HBO组(n=5)。HBO治疗:将荷瘤鼠置于无特殊病原体的HBO-IVC装置内,每天1次1小时HBO治疗。ACNU治疗:给予30 mg/kg腹腔注射,每周1次,共3次。实验结束时取移植瘤组织,q PCR法检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶9(matrix metalloprotein 9,MMP9)、低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和内皮糖蛋白(endoglin,CD105)的mRNA转录情况。结果对照组(n=10)移植瘤质量为(5.28±1.78)g,HBO组(n=5)为(3.47±1.57)g,ACNU组(n=5)为(2.20±0.12)g,两组与对照组比较差异均有统计学意义(P=0.008,P=0.000)。ACNU+HBO组(n=5)为(1.73±0.63)g,与对照组及ACNU组比较差异均有统计学意义(均P=0.004)。HBO+ACNU组的肿瘤组织坏死减轻,宿主源性免疫炎性细胞减少。TNF-α、MMP9、HIF-1α和CD105的mRNA转录水平在ACNU和HBO+ACNU组下降。结论 ACNU联合HBO治疗荷胶质瘤裸小鼠皮下移植瘤有效,HBO联合ACNU疗效更明显,其机制可能与抑制肿瘤相关炎性细胞浸润、TNF-α、MMP9、HIF-1α和CD105的表达有关。

Objective To investigate the efficacy of hyperbaric oxygen （HBO） combined with chemotherapy in treatment of human glioma - bearing nude mice. Methods Human glioma tissues were inoculated into nude mice subcutaneously. From d3 of tumor inoculation, tumor - bearing mice received HBO therapy for 1 h/d, meanwhile 30 mg/kg nimustine （ACNU） was injected intraperitoneally once per week for 3 w. After the end of the experiment,the mRNA levels of tumor necrosis factor-or （TNF-α） ,matrix metalloprotein 9 （MMP9） , hypoxia inducible factor-let（HIF-1α） and CD105 in exnograft tissue were detected by qPCR method. Results The weights of transplanted tumor after therapy were （5.28 ± 1.78 ） g in blank control group, （ 3.47 ± 1.57 ） g in HBO group ; （2.20 ± 0.12） g in ACNU group and （ 1.73 ± 0. 63 ） g in ACNU ＋ HBO combined group. There were significant differences between blank control and other treatment groups and between ACNU and ACNU ＋ HBO combined groups （ P 〈 0.01 ）. Tumor necrosis and the level of host-derived immune inflammatory cells were reduced in ACNU and ACNU ＋ HBO combined groups. Compared to blank control group, the mRNA levels of TNF-α, MMP9, HIF-1α and CD105 in ACNU and HBO ＋ ACNU groups decreased significantly.Conclusion Hyperbaric oxygen combined chemotherapy has significant antitumor effect in xenograft model,which may be related to the inhibition of inflammatory response in tumor - bearing mice.