Abstract: Objective   To investigate the stimulating effect of exogenous hydrogen sulfide (H2S) on angiogenesis in glioblastoma (GBM) and the role of matrix metalloproteinases-2 (MMP-2) in the process. Methods   20 adult Sprague–Dawley (SD) rats were randomly divided into 2 groups of 10 rats of each, which were glioma group (C6 glioma cell intracerebral implantation) and glioma-H2S group (C6 glioma cell intracerebral implantation and NaHS intraperitoneal injection). The tumor-bearing rat model was established by intracerebral injection of rat C6 glioma cell line, and an intraperitoneal injection of sodium hydrosulfide (NaHS), an exogenous H2S donor was administrated after 1 week of intracerebral injection in glioma-H2S rats. Food and water were freely available during all phases of the experiment. 3 weeks post intracerebral injection, all the rats were decapitated and the brains were removed. HE staining was performed to confirm and observe the tumor as well as the immunohistochemical analysises on CD34 and MMP-2 were carried out, respectively. The microvessel density (MVD) in GBM was represented by CD34 expressing and assessed respectively. Results   HE staining showed that the implanted tumors were predominantly spheroid with clear border and no capsule could be detected. Pseudopalisades and tumor cavity were clearly observed and the neovascular proliferations were also observed in two groups. All these phenomena were more markedly in glioma-H2S group. Immunohistochemical analysis exhibited that the CD34 and MMP-2 expressions were obviously increased after NaHS intraperitoneal injection in glioma-H2S rats (P＜0.001). The MVD of glioma-H2S group was higher than that of glioma group. Conclusion   Exogenous H2S serves as a stimulator of angiogenesis in the development of rat GBM. The tumor microenvironment was involved in the stimulating mechanisms included the promotion of endothelial cell proliferation and the increase of MMP-2 expression.

Key words: hydrogen sulfide, neovascularization, pathologic, MMP-2, antigens, CD34, immunohistochemistry, 免疫组织化学