硫酸右旋糖苷通过下调血管内皮生长因子/血管内皮生长因子受体2表达和M2型巨噬细胞浸润抑制胃癌血管生成的研究  

Dextran sulfate inhibits angiogenesis of gastric cancer by down-regulating VEGF/VEGFR2 expression and M2 macrophage infiltration

作　　者：郭嘉欣 李梦琪 尚静 焦龙杏 侯绍章 徐远义 黄允宁[2] GUO Jiaxin;LI Mengqi;SHANG Jing;JIAO Longxing;HOU Shaozhang;XU Yuanyi;HUANG Yunning(Department of Pathology,Ningxia Medical University,Yinchuan 750000,China;不详)

机构地区：[1]宁夏医科大学基础医学院病理学系,银川750000 [2]宁夏回族自治区人民医院胃肠外科,银川750000

出　　处：《实用医学杂志》2020年第17期2365-2370,共6页The Journal of Practical Medicine

基　　金：宁夏回族自治区重点研发项目(编号:2019BEG03007,2018BEG03010);宁夏自然科学基金项目(编号:2020AAC03184)。

摘　　要：目的研究硫酸右旋糖苷(dextran sulfate,DS)对裸鼠腹腔胃癌转移瘤中M2型巨噬细胞、血管生成和血管内皮生长因子(VEGF)/血管内皮生长因子受体2(VEGFR2)的影响。方法取34例人胃癌及12例癌旁组织标本,采用免疫组织化学及免疫荧光双染检测胃癌及癌旁组织中CD163(M2型巨噬细胞标记物)及CD34(代表微血管密度MVD)的表达;构建裸鼠胃癌腹腔种植转移模型DS组和对照组,14 d后观察裸鼠腹腔成瘤情况,采用免疫组织化学检测两组转移瘤CD163、CD34的表达,Western blot检测两组转移瘤CD163、VEGF和VEGFR2的表达。结果人胃癌组织免疫组化及免疫荧光结果显示,胃癌组织中M2型巨噬细胞浸润数量和微血管密度(MVD)显著高于癌旁组织(P<0.001),且M2型巨噬细胞浸润数量与MVD呈正相关(r=0.7013,P<0.0001)。裸鼠腹腔种植转移模型显示DS组肿瘤的数量明显少于对照组(P=0.017);裸鼠免疫组化结果显示,DS组M2型巨噬细胞数量和MVD显著少于对照组(P<0.001);裸鼠组织Western blot结果显示DS组CD163、VEGF和VEGFR2蛋白表达较对照组明显降低(P=0.002、0.001、0.037)。结论硫酸右旋糖苷通过减少裸鼠转移瘤中M2型巨噬细胞浸润和VEGF、VEGFR2的表达抑制血管生成,进而抑制胃癌细胞腹腔种植转移。Objective To investigate the effects of Dextran sulfate(DS)on M2-type macrophages,angiogenesis and VEGF/VEGFR2 in nude mice with abdominal metastasis tumor of gastric cancer.Methods34 samples of human gastric cancer and 12 samples of para-carcinoma tissues were collected,the expressions of CD163(M2-type macrophage marker)and CD34(representing microvascular density MVD)were detected byimmunohistochemistry and immunofluorescence assay.Abdominal metastasis of gastric cancer models of nude micewas constructed and divided into DS group and control group.Abdominal tumor formation was observed after14 dayslater.Immunohistochemistry was used to detect the expressions of CD163 and CD34 and Western blot was detect theexpressions of CD163,VEGF and VEGFR2 in two groups of metastatic tumors.ResultsThe number of M2-typemacrophage and MVD in gastric cancer tissue was significantly higher than in para-carcinoma tissue(P<0.001),and the degree of M2-type macrophage infiltration was positively correlated with MVD(r=0.7031,P<0.0001).Model of abdominal metastasis in nude mice showed that the number of tumors in the DS group were significantly lessthan that in control group(P=0.014);the number of M2-type macrophages and MVD in the DS group weresignificantly less than the control group(P<0.001);Western blot results showed that the expression of CD163,VEGF and VEGFR2 protein in DS group were significantly decreased,when compared with the control group(P=0.002,0.001,0.037).ConclusionsDS inhibits angiogenesis by reducing M2-types macrophage infiltration andthe expression of VEGF and VEGFR2 in metastatic tumors of nude mice,and inhibiting the intraperitonealimplantation and metastasis of gastric cancer cells.

关 键 词：硫酸右旋糖苷 血管生成 M2型巨噬细胞 胃癌腹腔种植转移 VEGF/VEGFR2 

分 类 号：R735.2[医药卫生—肿瘤]