納洛酮復(fù)合嗎啡對裸鼠人胃癌皮下瘤生長的影響
本文關(guān)鍵詞: 嗎啡 納洛酮 胃癌 皮下瘤 出處:《臨床麻醉學(xué)雜志》2017年03期 論文類型:期刊論文
【摘要】:目的觀察納洛酮復(fù)合嗎啡對裸鼠人胃癌皮下瘤生長的影響。方法建立裸鼠人胃癌MGC-803細(xì)胞皮下瘤模型,將50只裸鼠隨機分為五組:對照組(C組)、生理鹽水組(S組)、20mg/kg嗎啡組(M組)、1mg/kg納洛酮組(N組)、1 mg/kg納洛酮+20 mg/kg嗎啡組(NM組),每組10只。成瘤后,C組不作任何處理;S、M、N組裸鼠每天在右下腹分別腹腔注射生理鹽水1.5ml/kg、嗎啡20mg/kg或納洛酮1mg/kg;NM組裸鼠每天在右下腹先腹腔注射納洛酮1mg/kg,30min后再給予嗎啡20mg/kg;連續(xù)注射14d。每2天測量1次腫瘤的長徑和短徑,計算腫瘤相對體積(RTV);用藥結(jié)束后拉頸處死裸鼠,采用透射電鏡觀察腫瘤組織的結(jié)構(gòu)變化,免疫組化、半定量逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)和Western blot法檢測腫瘤組織中Cyclin D1、血管內(nèi)皮生長因子(VEGF)、基質(zhì)金屬蛋白酶9(MMP-9)的表達(dá)。結(jié)果 M組裸鼠皮下瘤RTV為(2.21±0.62)%,明顯小于C組的(3.16±0.68)%、S組的(2.98±0.61)%、N組的(3.16±0.35)%和NM組的(2.64±0.37)%(P0.05);NM組裸鼠皮下瘤RTV明顯小于C、S和N組(P0.05)。電鏡下,C、S、N及NM組皮下瘤組織結(jié)構(gòu)基本正常,M組皮下瘤細(xì)胞出現(xiàn)胞漿空泡化、核膜破裂、核染色質(zhì)邊集等。M組裸鼠皮下瘤組織內(nèi)Cyclin D1、VEGF、MMP-9陽性染色腫瘤細(xì)胞、mRNA和蛋白的表達(dá)明顯低于C組(P0.05);NM組裸鼠皮下瘤組織內(nèi)Cyclin D1、VEGF、MMP-9陽性染色腫瘤細(xì)胞、mRNA和蛋白的表達(dá)明顯高于M組(P0.05)。結(jié)論嗎啡可抑制裸鼠人胃癌皮下瘤的生長,納洛酮可拮抗這一作用,其機制可能與其調(diào)節(jié)Cyclin D1、VEGF、MMP-9的表達(dá)有關(guān)。
[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 鹵0.62cm, which was significantly lower than that in group C (3.16 鹵0.68S). The RTV of subcutaneous tumor in group N and group NM were 3.16 鹵0.35% and 2.64 鹵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.
【作者單位】: 廣西醫(yī)科大學(xué)第一附屬醫(yī)院麻醉科;
【基金】:國家自然科學(xué)基金(81560500,81160289) 廣西自然科學(xué)基金(2013GXNSFBA019156) 廣西科學(xué)研究與技術(shù)開發(fā)計劃課題(桂科攻1355005-1-6)
【分類號】:R614;R735.2
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