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丙氨瑞林對人子宮內(nèi)膜癌裸鼠皮下移植瘤的生長及Fli-1表達(dá)的影響

發(fā)布時間:2018-04-03 08:48

  本文選題:子宮內(nèi)膜癌 切入點(diǎn):移植瘤 出處:《山西醫(yī)科大學(xué)》2015年碩士論文


【摘要】:目的:通過在裸鼠皮下建成人子宮內(nèi)膜癌的腫瘤模型,再對實驗裸鼠隨機(jī)分組后用不同劑量的丙氨瑞林干預(yù),觀察不同濃度的藥物干預(yù)后人子宮內(nèi)膜癌體外移植腫瘤的增長狀況和移植腫瘤中的Fli-1蛋白表達(dá)情況。方法:把HEC-1B人子宮內(nèi)膜癌細(xì)胞株(HEC-1B于體外培養(yǎng))接種到4-6周齡雌性裸鼠右上肢近腋皮下,建立腫瘤模型。然后將裸鼠隨機(jī)分為4組(每組8只),即丙氨瑞林藥物高、中、低劑量組及生理鹽水對照組。創(chuàng)建模型1周后對各組進(jìn)行丙氨瑞林干預(yù),每天肌肉注射藥物1次,藥量為每次0.2ml。低、中、高劑量組的藥物濃度分別為20μg/kg、40μg/kg、80μg/kg,同時對照組給予肌注0.2ml生理鹽水。嚴(yán)密觀測腫瘤的增長情況,并察看裸鼠一般狀況。4周后處死荷瘤小鼠,將腫瘤完整取出,計算各治療組的抑瘤率,隨后應(yīng)用免疫組化察瘤細(xì)胞中Fli-1(弗里德白血病病毒插入位點(diǎn)1)的表達(dá)。結(jié)果:(1)荷瘤小鼠的一般情況裸鼠在建模之初,活動、反應(yīng)好,體重變化不明顯;在瘤體逐漸增大的過程中,裸鼠的反應(yīng)力和活動力逐漸下降,體重日漸減輕。各治療組裸鼠的反應(yīng)力及體重都不同程度高于對照組。(2)藥物干預(yù)后體腫瘤體積隨藥物劑量的增大,增長曲線的斜率變小,反映腫瘤的增長速度逐漸減慢,腫瘤的增長受到明顯抑制。對照組、低、中、高劑量組腫瘤體積分別為:(1812.93±196.249mm3)、(1518.82±124.933mm3)、(1399.44±187.657mm3)、(1164.55±189.118mm3),各兩組間比較,用LSD-t檢驗,差異具統(tǒng)計意義(F值為18.604,P0.001)。低、中、高劑量組的抑瘤率為(14.76±4.904%)、(27.5±5.456%)、(36.77±2.67%),用LSD-t檢驗,實驗組各兩組間比較,且與對照組相比,差異均有統(tǒng)計學(xué)意義(F值為31.477,P0.001)。說明丙氨瑞林對腫瘤細(xì)胞增長起抑制性作用,且有劑量依賴性。(3)HE染色結(jié)果治療組中瘤細(xì)胞比較稀疏,能夠看到裂解的、固縮的和凋亡細(xì)胞;對照組中瘤細(xì)胞密集,清晰可見癌巢,腫瘤細(xì)胞核大深染,大量核分裂相,胞核與胞漿比例極其失調(diào)。(4)免疫組化結(jié)果移植瘤用不同劑量藥物干預(yù)后,隨劑量增加Fli-1蛋白表達(dá)量逐漸減少。對照組及丙氨瑞林各治療組腫瘤組織中Fli-1蛋白的灰度值分別為:對照組(118.1±4.241)、低劑量組(135.93±3.548)、中劑量組(147.51±6.755)、高低劑量組(168.84±5.202),與對照組比較,各治療組中Fli-1蛋白表達(dá)水平灰度值都有不等級別的增高,且不同劑量的組間比較采用LSD-t檢驗差異有統(tǒng)計學(xué)意義(F=140.196,P0.001)。結(jié)論:(1)丙氨瑞林在裸鼠移植瘤發(fā)展中起抑制作用,伴隨丙氨瑞林劑量增添的同時抑制作用越發(fā)明顯。(2)丙氨瑞林對腫瘤的抑制作用機(jī)制可能與下調(diào)移植瘤組織中Fli-1的表達(dá)有關(guān)。
[Abstract]:Objective: to establish a tumor model of human endometrial carcinoma in nude mice subcutaneously.To observe the growth of human endometrial carcinoma transplanted tumor in vitro and the expression of Fli-1 protein in transplanted tumor after different concentrations of drugs.Methods: HEC-1B human endometrial carcinoma cell line HEC-1B was cultured in vitro.Then the nude mice were randomly divided into 4 groups (8 rats in each group), that is, alanine high, middle and low dose groups and normal saline control group.One week after the model was established, each group was treated with alarelin. The drug was injected intramuscularly once a day, with a dose of 0.2 ml per day.The drug concentrations in the low, middle and high dose groups were 20 渭 g / kg ~ 40 渭 g / kg ~ 80 渭 g 路kg ~ (-1) respectively, while the control group was given 0.2ml saline intramuscularly.The tumor-bearing mice were killed after observing the general condition of the nude mice for 4 weeks, the tumor was removed completely, and the tumor inhibition rate of each treatment group was calculated.The expression of Fli-1 (Fli-1) was detected by immunohistochemistry.Results (1) the general situation of tumor-bearing mice was that at the beginning of modeling, the nude mice reacted well, but their body weight did not change obviously, while the reaction power and activity force of nude mice gradually decreased and their body weight gradually decreased during the process of tumor increasing.The response power and body weight of nude mice in each treatment group were higher than those in control group (P < 0.05). The volume of body tumor decreased with the increase of drug dose, and the slope of the growth curve became smaller, which indicated that the growth rate of tumor was slowing down gradually.The growth of the tumor was significantly inhibited.瀵圭収緇,

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