纳洛酮复合吗啡对裸鼠人胃癌皮下瘤生长的影响

发布时间：2018-03-01 00:03

本文关键词： 吗啡纳洛酮胃癌皮下瘤　出处：《临床麻醉学杂志》2017年03期 　论文类型：期刊论文

【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)%(P0.05);NM组裸鼠皮下瘤RTV明显小于C、S和N组(P0.05)。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(P0.05);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(P0.05)。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。
[Abstract]:Objective to observe the effect of naloxone combined with morphine on the growth of human gastric cancer subcutaneous tumor in nude mice. Fifty nude mice were randomly divided into five groups: control group (n = 10), control group (n = 10), saline group (n = 10), group S (n = 20 mg / kg morphine), group M (n = 1 mg / kg naloxone) and group N (n = 1 mg / kg naloxone 20 mg / kg morphine). Nude mice were injected intraperitoneally with normal saline 1.5ml / kg per day, morphine 20mg / kg or naloxone 1mg / kg NM group respectively. The nude mice were injected intraperitoneally with naloxone 1 mg / kg / kg for 30 minutes and then given morphine 20mg / kg for 14 consecutive days. The long and short diameter of tumor was measured once every 2 days. The relative volume of tumor was calculated and the neck-pulling nude mice were killed after treatment. The structural changes of tumor tissue were observed by transmission electron microscope. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of Cyclin D1, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in tumor tissues. Results the RTV of subcutaneous tumor in group M was 2.21 卤0.62cm, which was significantly lower than that in group C (3.16 卤0.68S). The RTV of subcutaneous tumor in group N and group NM were 3.16 卤0.35% and 2.64 卤0.37%, respectively. The RTV of subcutaneous tumor in NM group was significantly lower than that in group C (S) and group N (P 0.05). The cytoplasmic vacuolation was observed in subcutaneous tumor cells of group N and group N under electron microscope. Nuclear membrane rupture, The expression of Cyclin D _ (1) VEGF _ (9) -positive staining mRNA and protein in subcutaneous tumor tissue of nude mice in group M was significantly lower than that in group C (P 0.05). The expression of Cyclin D _ (1) VEGFFMP _ 9 positive staining tumor cells in nude mice was significantly higher than that in group C (P 0.05). Conclusion morphine can inhibit the growth of human gastric cancer subcutaneous tumor in nude mice. Naloxone can antagonize this effect, and its mechanism may be related to its regulation of the expression of Cyclin D 1 and VEGFU MMP-9.
【作者单位】：广西医科大学第一附属医院麻醉科;
【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)
【分类号】：R614;R735.2

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