目的探讨外源性硫化氢(H2S)对大鼠恶性胶质瘤内血管新生的影响。方法成年雄性sD大鼠20只,随机分成肿瘤组和肿瘤-H2S组,每组10只。2组大鼠均脑内注射C6细胞,1周后,肿瘤组腹腔注射生理盐水,肿瘤一HzS组腹腔注射外源性H:S,即硫氢化钠(NariS)溶液。均正常饲养,3周后断头取脑。组织病理学观察瘤体结构以及瘤内微血管生成情况,免疫组化评估瘤体内CD34及基质金属蛋白酶(MMP)-2的表达情况;并计数瘤内微血管密度(MVD)。结果肿瘤组与肿瘤-H2S组大鼠脑内均可见明显的肿瘤组织;与对侧正常脑组织相比,瘤内毛细血管明显增多;肿瘤-H2S组瘤体内有更多的CD34和MMP-2表达,肿瘤-H2S组瘤内MVD明显高于肿瘤组(均P〈0.01)。结论外源性H2S能促进大鼠恶性胶质瘤内的血管新生,其机制可能与H2S促进瘤体内MMP-2的表达有关。
Objective To investigate the stimulating effect of exogenous hydrogen sulfide (H2S) on angiogenesis in glioblastoma (GBM). Methods Twenty adult Sprague-Dawley (SD) rats were randomly divided into two groups, glioma group (C6 glioma cell intracerebral implantation, n=10) and glioma-H2S group (C6 glioma cell intracerebral implantation and sodium hydrosulfide (NariS) intraperitoneal injection, n=10). The tumor-bearing rat model was established by intracerebral injection of rat C6 glioma cells. After one week, normal saline was injected in glioma group and NailS was injected in glio- ma-H2S group. Food and water were freely available during all phases of the experiment. After three weeks, rats were decapi- tated and brains were removed. HE staining was performed to show tumor structure and intratumoral angiogenesis. The immu- nohistochemical analysis was used to detect the expressions of CD34 and MMP-2, respectively. The microvessel density (MVD) in GBM was also measured. Results HE staining showed that the implanted tumors were predominantly spheroid with clear border and no capsule could be detected. The neovascular proliferations were observed in tumors. There were high- er expressions of CD34 and MMP-2 in glioma-H~S group. The value of MVD was significantly higher in glioma-H2S group than that of glioma group (P 〈 0.01). Conclusion Exogenous H2S serves as a stimulator of angiogenesis in the development of rat GBM, which may be related with the increased MMP-2 expression promoted by H2S.