芬太尼对裸鼠人胃癌皮下瘤VEGF-A和MMP-9表达的影响  

Effect of fentanyi on expression of VEGF-A and MMP-9 in subcutaneous tumor cancer in nude mice

作　　者：陈秋妙 管恩健[1] 杨一兰[1] 利莉[1] 谢玉波[1] 

机构地区：[1]广西医科大学第一附属医院麻醉科,南宁市530021

出　　处：《中华麻醉学杂志》2016年第4期438-441,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81560500,81160289）;广西科学研究与技术开发计划课题（桂科攻1355005-1-6）;广西自然科学基金（2013GXNSFBA019156）

摘　　要：目的评价芬太尼对裸鼠人胃癌皮下瘤血管内皮生长因子A（VEGF—A）和基质金属蛋白酶9（MMP．9）表达的影响。方法SPF级雄性BALB／C裸鼠30只，4～5周龄，体重15～20g，建立裸鼠人胃癌MGC-803细胞皮下瘤模型，采用随机数字表法将其分为6组（n=5）：对照组（c组）、生理盐水组（Ns组）和芬太尼0．05、0．10、0．20、0．40 mg／kg组（F1组、F2组、F3组和F4组）。F1组、F2组、F3组和F4组分别腹腔注射相应剂量芬太尼，1次／d，连续14d；NS组给予等容量生理盐水1．5ml／kg。停止给药后1d处死裸鼠，取肿瘤组织，透射电子显微镜观察皮下瘤的超微结构，采用免疫组织化学染色法和Western blot法测定VEGF—A和MMP-9的表达，采用RT—PCR法测定VEGF．A和MMP-9的mRNA表达。结果c组和NS组皮下瘤组织细胞形态结构未见异常，F1组、F2组、F3组和F4组皮下瘤组织细胞呈现核肿胀、染色质边集、核碎裂甚至出现凋亡小体。与C组比较，F1组、F2组、F3组和F4组皮下瘤组织VEGF—A和MMP-9及其mRNA表达下调（P〈0．05），NS组各指标比较差异无统计学意义（P〉0．05）；F1组、F2组、F3组和F4组间皮下瘤组织VEGF—A和MMP-9及其mRNA表达比较差异无统计学意义（P〉0．05）。结论芬太尼抑制裸鼠人胃癌皮下瘤生长和转移的机制与下调VEGF—A和MMP-9的表达有关。Objective To evaluate the effect of fentanyl on the expression of vascular endothelial growth factor A （VEGF-A） and matrix metallopeptidase-9 （MMP-9） in the subcutaneous tumor of human gastric cancer in nude mice. Methods Thirty SPF male BALB/C nude mice, aged 4-5 weeks, weighing 15-20 g, in which the model of subcutaneous tumor of human gastric cancer cell line MGC-803 was estab- lished, were randomly divided into 6 groups （n= 5 each） using a random number table： control group （C group）, normal saline group （NS group） and fentanyl 0.05, 0.10, 0.20 and 0.40 mg/kg groups （FI_4 groups）. The mice in group C received no treatment. Fentanyl 0.05, 0.10, 0.20 and 0.40 mg/kg were in- traperitoneally injected once a day for 14 consecutive days in Fl_4 groups, respectively, while the equal vol- ume of normal saline 1.5 ml/kg was given instead of fentanyl in group NS. The nude mice were sacrificed on 1 day after the end of administration, and the tumor tissues were obtained for examination of the ultrastruc- ture of subcutaneous tumor （with a transmission electron microscope） and for detection of the expression of VEGF-A and MMP-9 （ by immunohistochemistry and Western blot） and expression of VEGF-A and MMP-9 mRNA （by real-time reverse transcriptase polymerase chain reaction）. Results No abnormality in the morphology of the subcutaneous tumor cells was observed in C and NS groups. The swollen nucleus, ehromatin margination, nuclear fragmentation and apoptotic bodies were found in the subcutaneous tumor cells in F~_4 groups. Compared with group C, the expression of VEGF-A and MMP^9 protein and mRNA was sig- nificantly down-regulated in F~_4 groups （P〈0.05） , and no significant change was found in each parameter mentioned above in group NS （P〉0.05）. There was no significant difference in the expression of VEGF-A and MMP-9 protein and mRNA among FI_4 groups （P〉0.05）. Conclusion The mechanism by which fent- anyl inhibits the growth and metastasis of subcutaneous tumor cells

关 键 词：芬太尼 胃肿瘤 血管内皮生长因子A 基质金属蛋白酶9 

分 类 号：R614[医药卫生—麻醉学] R735.2[医药卫生—外科学]