Ding Jian-Bo, Chen Jun-Rui, Xu Hong-Zhi, Qin Zhi-Yong
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Chin Med J (Engl). 2015 Dec 5;128(23):3197-203. doi: 10.4103/0366-6999.170278.
Numerous studies have confirmed that hyperbaric oxygen (HBO) in combination with radiotherapy or chemotherapy may increase the efficacy of radiotherapy or chemotherapy in patients with glioma. However, whether HBO therapy alone may inhibit or promote the growth of malignant tumors remains controversial. This study aimed to investigate the effect of HBO on the growth of glioma in rats, and the impact of HBO on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α), angiogenesis, and apoptosis of glioma cells.
Male Sprague-Dawley rats were treated with or without HBO after glioma cell inoculation and followed for up to 16 days postinoculation. Rats were randomized to receive bilateral forelimb function tests (n = 20 per group) and head magnetic resonance imaging (n = 5 per group). Differences between HBO and control groups were tested using 2-sample independent t-tests and changes over time within treatment groups were analyzed using a repeated measurement analysis of variance with Bonferroni correction. The effect of HBO on the expression of VEGF, HIF-1α, von Willebrand factor, angiogenesis, and tumor cell apoptosis were also examined (n = 5 per group).
Forelimb function scores were reduced in both HBO-treated and control groups. HBO-treated rats had significantly larger tumor volume and more water in the cerebellum compared with control rats. The intratumoral expression of VEGF was significantly higher in HBO-treated rats compared with control rats (23.2% vs. 13.3%, P = 0.002). HIF-1α was significantly increased in HBO-treated rats compared with controls in the expression of both intratumoral (72.7% vs. 54.9%, P = 0.001) and peritumoral (2.6% vs. 1.9%, P = 0.003) cells. The intratumoral microvessel density (MVD) was significantly higher in the HBO group (15.6 vessels/field vs. 4.4 vessels/field, P < 0.001), and the peritumoral MVD was not significantly different between the two groups (P > 0.05). Apoptosis was significantly lower in HBO-treated rats compared with controls (44.4% vs. 82.8% for intratumoral; 10.1% vs. 77.5% for peritumoral, both P < 0.001).
The current results demonstrate that HBO alone may promote tumor growth, and is therefore not suitable to treat patients with gliomas with neurological deficits or disorders with HBO alone. If HBO must be used as a mean of rehabilitation, it is recommended that HBO should be combined with radiotherapy or chemotherapy.
大量研究证实，高压氧（HBO）联合放疗或化疗可提高胶质瘤患者放疗或化疗的疗效。然而，单纯HBO治疗是否会抑制或促进恶性肿瘤生长仍存在争议。本研究旨在探讨HBO对大鼠胶质瘤生长的影响，以及HBO对胶质瘤细胞血管内皮生长因子（VEGF）和缺氧诱导因子1α（HIF-1α）表达、血管生成和凋亡的影响。
雄性Sprague-Dawley大鼠接种胶质瘤细胞后接受或不接受HBO治疗，并在接种后随访长达16天。将大鼠随机分组接受双侧前肢功能测试（每组20只）和头部磁共振成像（每组5只）。使用两独立样本t检验比较HBO组和对照组之间的差异，并使用经Bonferroni校正的重复测量方差分析来分析治疗组内随时间的变化。还检测了HBO对VEGF、HIF-1α、血管性血友病因子表达、血管生成和肿瘤细胞凋亡的影响（每组5只）。
HBO治疗组和对照组的前肢功能评分均降低。与对照大鼠相比，HBO治疗的大鼠肿瘤体积明显更大，小脑含水量更多。与对照大鼠相比，HBO治疗的大鼠肿瘤内VEGF表达明显更高（23.2%对13.3%，P = 0.002）。与对照组相比，HBO治疗的大鼠肿瘤内（72.7%对54.9%，P = 0.001）和肿瘤周围（2.6%对1.9%，P = 0.003）细胞中HIF-1α表达均显著增加。HBO组肿瘤内微血管密度（MVD）明显更高（15.6个血管/视野对4.4个血管/视野，P < 0.001），两组肿瘤周围MVD无显著差异（P > 0.05）。与对照组相比，HBO治疗的大鼠凋亡明显更低（肿瘤内44.4%对82.8%；肿瘤周围10.1%对77.5%，均P < 0.001）。
目前的结果表明，单纯HBO可能促进肿瘤生长，因此不适合单独用HBO治疗有神经功能缺损或障碍的胶质瘤患者。如果必须将HBO用作康复手段，建议将HBO与放疗或化疗联合使用。
