天津医药

• 实验研究 •    下一篇

外源性 H2S 促进大鼠恶性胶质瘤的血管新生

李战永1,孔德强2,杨卓3,张涛4   

  1. 1. 河北省廊坊师范学院生命科学学院
    2. 河北省廊坊市人民医院神经内科
    3. 天津南开大学医学院
    4. 南开大学生命科学学院
  • 收稿日期:2012-09-11 修回日期:2013-03-25 出版日期:2013-08-15 发布日期:2013-08-15
  • 通讯作者: 张涛

Exogenous Hydrogen Sulfide Stimulates the Angiogenesis of Rat Glioblastoma

LI Zhanyong 1,KONG Deqiang 1,YANG Zhuo 2,ZhangTao 2   

  1. 1. The People’ s Hospital of Langfang City
    2. College of Life Sciences, Nankai University, Tianjin 300071, China
  • Received:2012-09-11 Revised:2013-03-25 Published:2013-08-15 Online:2013-08-15
  • Contact: ZhangTao

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摘要： 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-H2S组腹腔注射外源性H2S，硫氢化钠（NaHS）溶液。2组大鼠均正常饲养，脑内注射3周后分别断头取脑。组织病理学观察瘤体结构以及瘤内微血管生成情况，免疫组化实验评估瘤体内CD34及基质金属蛋白酶（MMP）-2的表达情况；通过CD34的表达反映瘤内微血管密度（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；免疫组化测定结果显示，肿瘤-H2S组瘤体内有更多的CD34和MMP-2表达（P＜0.001），肿瘤-H2S组瘤内微血管密度显著高于肿瘤组（P＜0.001）。结论 外源性H2S能促进大鼠恶性胶质瘤内的血管新生，其机制与H2S促进瘤体内MMP-2的表达有关。

关键词: 硫化氢, 神经胶质瘤, 新生血管化, 病理性, 基质金属蛋白酶2, 抗原, CD34, 免疫组织化学

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