纳洛酮复合吗啡对裸鼠人胃癌皮下瘤生长的影响  

Effect of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice

作　　者：王昊[1] 覃怡[1] 谢玉波[1] 利莉[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：《临床麻醉学杂志》2017年第3期277-280,共4页Journal of Clinical Anesthesiology

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

摘　　要：目的观察纳洛酮复合吗啡对裸鼠人胃癌皮下瘤生长的影响。方法建立裸鼠人胃癌MGC-803细胞皮下瘤模型,将50只裸鼠随机分为五组:对照组(C组)、生理盐水组(S组)、20mg/kg吗啡组(M组)、1mg/kg纳洛酮组(N组)、1 mg/kg纳洛酮+20 mg/kg吗啡组(NM组),每组10只。成瘤后,C组不作任何处理;S、M、N组裸鼠每天在右下腹分别腹腔注射生理盐水1.5ml/kg、吗啡20mg/kg或纳洛酮1mg/kg;NM组裸鼠每天在右下腹先腹腔注射纳洛酮1mg/kg,30min后再给予吗啡20mg/kg;连续注射14d。每2天测量1次肿瘤的长径和短径,计算肿瘤相对体积(RTV);用药结束后拉颈处死裸鼠,采用透射电镜观察肿瘤组织的结构变化,免疫组化、半定量逆转录-聚合酶链反应(RT-PCR)和Western blot法检测肿瘤组织中Cyclin D1、血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP-9)的表达。结果 M组裸鼠皮下瘤RTV为(2.21±0.62)%,明显小于C组的(3.16±0.68)%、S组的(2.98±0.61)%、N组的(3.16±0.35)%和NM组的(2.64±0.37)%(P<0.05);NM组裸鼠皮下瘤RTV明显小于C、S和N组(P<0.05)。电镜下,C、S、N及NM组皮下瘤组织结构基本正常,M组皮下瘤细胞出现胞浆空泡化、核膜破裂、核染色质边集等。M组裸鼠皮下瘤组织内Cyclin D1、VEGF、MMP-9阳性染色肿瘤细胞、mRNA和蛋白的表达明显低于C组(P<0.05);NM组裸鼠皮下瘤组织内Cyclin D1、VEGF、MMP-9阳性染色肿瘤细胞、mRNA和蛋白的表达明显高于M组(P<0.05)。结论吗啡可抑制裸鼠人胃癌皮下瘤的生长,纳洛酮可拮抗这一作用,其机制可能与其调节Cyclin D1、VEGF、MMP-9的表达有关。Objective To observe the effects of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice.Methods The model of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice was established.Fifty nude mice were randomly divided into 5 groups：control group（group C）,normal saline group（group S）,20mg/kg morphine group（group M）,and 1 mg/kg naloxone group（group N）,and 1mg/kg naloxone＋20mg/kg morphine group（group NM）.The mice in group C received no treatment,while the mice in group S,group M,group N and group NM were injected with 1.5ml/kg saline,20mg/kg morphine,1mg/kg naloxone,and 1mg/kg naloxone＋20mg/kg morphine per day,respectively.The caliper was used to measure the tumor sizes every the other day.The mice in each group received intraperitoneal injection of the drugs for 2week.Then the relative volume（RTV）of tumor was calculated.The expression of Cyclin D1,VEGF,MMP-9mRNA and proteins were detected by semiquantitative reverse transcription polymerase chain reaction（RT-PCR）,immunochemistry staining and Western blot.Results RTV in group M（2.21±0.62）% was significantly lower than that in group C（3.16±0.68）%,group S（2.98±0.61）%,group N（3.16±0.35）% and group NM（2.64±0.37）%（P〈0.05）.RTV in group NM was significantly lower than that in group C,group S and group N（P〈0.05）.Compared with group C,the expression of Cyclin D1,VEGF,and MMP-9 in group M were significantly decreased（P〈0.05）.The organizational structure of the subcutaneous tumor in groups C,S,N and NM was almost normal.Cytoplasm vacuolization,disruption of nuclear membrane and chromatin margination were occured in group M.While the level of Cyclin D1,VEGF,and MMP-9 in group NM was increased compared to group M（P 0.05）.Conclusion Morphine could inhibit the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice by downregulating the expression of Cyclin D1,VEGF,and MMP-9.Naloxone could a

关 键 词：吗啡 纳洛酮 胃癌 皮下瘤 

分 类 号：R614[医药卫生—麻醉学] R735.2[医药卫生—外科学]