血管活性肠肽与胃腺癌炎性细胞中NKG2D分子、衔接体蛋白质10、细胞外信号调节激酶表达的相关性研究  

Correlation between vasoactive intestinal peptide and expression of NKG2D, adaptor protein 10 and extracellular signal-regulated kinase in inflammatory cells of gastric adenocarcinoma

作　　者：王翀[1] 李国华[1] 杨霞[1] 吴平安[1] 

机构地区：[1]南昌大学第一附属医院消化科,330006

出　　处：《中华消化杂志》2013年第8期544-549,共6页Chinese Journal of Digestion

基　　金：国家自然科学基金（30760086）

摘　　要：目的观察NKG2D和相关信号分子衔接体蛋白质10（DAP10）、ERK在胃腺癌和癌旁组织炎性细胞内的表达情况，以及血管活性肠肽（VIP）对健康志愿者NK细胞中NKG2D、DAP10、ERK表达的影响。初步分析VIP对炎性细胞，尤其是NK细胞中NKG2D及其相关信号分子的作用。方法通过免疫组织化学方法检测36对胃腺癌组织和癌旁正常组织炎性细胞中NKG2D分子、DAP10、ERK表达情况。使用补体裂解法原代分离、纯化30名健康志愿者外周血NK细胞，通过免疫细胞化学和RTPCR方法检测VIP干预前后NK细胞中NKG2D分子、DAP10、ERK表达情况。两组间计量资料比较用t检验。计数资料采用秩转换的非参数检验（Kruskal—wallisH检验）。结果胃腺癌炎性细胞中NKG2D分子、DAP10和ERK的蛋白表达强度显著低于癌旁正常组织（H=30．640、24．910、20．320，P均〈0．01）。且NKG2D分子、DAP10和ERK在低分化（H=4．049、11．830、8．118）、Ⅲ至Ⅳ期（H=4．275、11．560、7．686），NKG2D分子和ERK在有淋巴结转移（H=6．513、6．064）的胃腺癌中蛋白表达更低（P均d0．05），但与患者性别、年龄、病变部位无明显的相关性（P均〉0．05）。VIP作用后的NK细胞中NKG2D分子、DAP10、ERK的表达降低（蛋白：H=12．438、4．798、13．745，mRNA：F=337．640、638．579、1055．015，P均〈0．05）。结论胃癌组织可能通过分泌VIP下调NK细胞中NKG2D、DAP10、ERK的表达，参与胃癌的免疫逃逸。Objective To investigate the expression of NKG2D and related signaling molecules adaptor protein（DAP10） and extracellular signal-regulated kinase （ERK） in the inflammatory cells of gastric adenocarcinoma and para-carcinoma tissues, the effects of vasoactive intestinal peptide（VIP） on the expression of NKG2D, DAP10 and ERK in natural killer （NK） cells of healthy volunteers. Methods The expression of NKG2D, DAP10 and ERK in the inflammatory cells of 36 gastric adenocarcinoma and para-carcinoma tissues were detected by immunohistochemistry. The peripheral blood NK cells of healthy volunteers were isolated and purified with CDC method. The expressions of NKG2D, DAP10 and ERK in NK cells were determined by immunocytochemistry and reverse transcription-polymerase chain reaction（RT-PCR） methods before and after VIP intervention. The t-test was used for comparison between two groups and rank transformation nonparametric test （Kruskal-Wallis H test） for count data analysis. Results The expression levels of NKG2D, DAP10 and ERK in the inflammatory cells of gastric adenocarcinoma were significantly lower than those of para-carcinomatissues （H=30. 640, 24. 910, 20. 320, all P%0. 01）. The expression levels of NKG2D, DAP10 and ERK were much lower in poorly differentiated gastric adenocarcinoma （H = 4. 049, 11. 830, 8. 118）, at stage 111 -- IV （H=4. 275, 11. 560, 7. 686）, and the expression levels of NKG2D, ERK were lower with lymph nodes metastasis （H=6. 513, 6.064, all P%0.05）. The expression levels of NKG2D, DAP10 and ERK in gastric adenocarcinoma tissues and inflammatory cells were not correlated with gender, age and the location of lesions （all P）0.05）. The expression levels of NKG2D, DAP10 and ERK in NK cells was decreased after VIP intervention （protein： H= 12.438, 4.798, 13.745, mRNA： F=337. 640, 638. 579, 1055.015, all P〈0. 05）. Conclusion Gastric adenocarcinoma may downregulate the expression of NKG2D, DAP10 and ERK in NK cells through VIP secretion, which may be

关 键 词：血管活性肠肽 杀伤细胞 天然 胃肿瘤 腺癌 DAP10蛋白 丝裂原激活蛋白激酶类 肿瘤逃逸 

分 类 号：R735.2[医药卫生—肿瘤]