摘要目的 探讨高压氧(HBO)联合胶质瘤化疗药宁得朗(ACNU)治疗胶质瘤干祖细胞SU3移植瘤的疗效.方法 将SU3移植于生长在独立送风系统小鼠笼(IVC)内的普通NC裸小鼠皮下.致瘤后,取肿瘤组织接种于全身发绿色荧光的NC裸小鼠皮下,第3天按数字表法随机分成4组:HBO组(7只)、ACNU+ HBO组(7只)、ACNU组(7只)和对照组(12只),前2组置于早先建立的无特殊病原体(SPF)的HBO-IVC装置内,每天1次每次100 min HBO治疗;第2、第3组按30 mg/kg ACNU腹腔注射,每周1次,共3次.每3d1次用游标卡尺测肿瘤体积和天平称荷瘤鼠体质量.实验结束时,测量肿瘤体积和质量,取部分组织行相关分子Rt-PCR检测,余下的制作病理切片.结果 各组移植瘤质量并与对照组比:ACNU+ HBO组为(2 252.86±1 062.54) mg (P=0.006);ACNU组为(1 914.28 ±744.55) mg(P =0.002);HBO组为(4 680.00±2 538.40) mg (P=0.925);对照组为(4 760.83±1 989.18) mg.移植瘤组织和分子病理方面:对照组肿瘤组织坏死性出血灶十分普遍,出血区域旁肿瘤血管较多,血管内皮细胞增生活跃;这种情况HBO组较少见,而ACNU、ACNU+ HBO组没有见到新鲜出血,陈旧性出血亦较少,血管增生相对不活跃,同时TNF-α和CD105的mRNA表达值较对照组明显低(分别为P=0.028,P=0.008).结论 ACNU联合HBO治疗荷人胶质瘤荧光裸小鼠皮下移植瘤有明显的抑制肿瘤生长的作用.虽然单独HBO治疗的抑瘤作用不明显,但无促进肿瘤生长作用.因此,恶性肿瘤患者进行康复治疗时,HBO辅助治疗不应视作禁忌性措施.

abstractsObjective To investigate the therapeutic effects of the chemotherapeutic drug ACNU combined with hyperbaric oxygen (HBO) in the treatment of transplantation tumor of glioma stem/progenitor cells SU3.Methods The SU3 cells were inoculated subcutaneously into general NC nude mice which were kept in an independent ventilated cages (IVC).Following the development of the tumor,the tumor-bearing mice were sacrificed,and tumor tissues were harvested,then,inoculated subcutaneously into transgenic green fluorescence protein (GFP) nude mice.On the third day,the animals were randomly divided into 4 groups:the HBO group (n =7),the ACNU + HBO group (n =7),the ACNU group (n =7) and the control group (n =12).The first 2 groups were placed in the HBO-IVC without specific pathogens and treated with HBO,1 session a day for a duration of 100 minutes.The animals in the second and third groups were administered with ACNU abdominally at a dosage of 30 mg/kg,once a week for a duration of 3 weeks.The tumor volume was measured with the vernier caliper and the body mass of tumor-bearing mice was weighed with the balance weight,once every 3 days.At the end of the experiment,some tissues were collected to perform RT-PCR detection,the remaining tissues were used for pathological sections.Results As compared with those of the control group,changes in the transplantation tumor mass of various groups were as follows:The tumor mass for the ACNU + HBO group was (2 252.86 ± 1 062.54) mg (P =0.006);the tumor mass for the ACNU group was (1 914.28 ±744.55) mg (P=0.002);that for the HBO group was (4 680.00 ±2 538.40) mg(P =0.925);and that for the control group was (4 760.83 ± 1 989.18) mg.Histopathological examination indicated that necrotic hemorrhage foci in tumor tissues could be frequently observed in the control group,and numerous neoformative vessels around the hemorrhagic site could also be found.Proliferation of vascular endothelial cells was quite active under microscopy.However,those pathological changes in the HBO group could scarcely be seen.In the ACNU and the ACNU plus HBO groups,there was no fresh hemorrhage,and neither was there remote hemorrhage.Vascular proliferation was relatively inactive.At the same time,the mRNA expression levels of TNF-α and CD105 were obviously lower than those of the control group (P =0.028,P =0.008).Conclusions ACNU coupled with HBO seemed to have marked tumor inhibitive effect on human glioma in the subcutaneous nude mice model.Though single HBO therapy produced little prohibitive effect on tumor growth,it failed to promote tumor growth either.For this reason,in the rehabilitation of patients with malignant tumor,HBO therapy should not be regarded as a taboo.